Biochemistry

Topic: Lipid Metabolism
Subtopic: Lipoproteins

Keyword Definitions

• Lipoproteins: Complexes of lipids and proteins that transport lipids in blood.

• HDL: High-density lipoprotein, removes cholesterol from tissues to liver.

• LDL: Low-density lipoprotein, carries cholesterol to tissues, atherogenic.

• VLDL: Very-low-density lipoprotein, transports triglycerides from liver.

• Chylomicrons: Largest lipoproteins, transport dietary triglycerides.

• Electrophoretic mobility: Movement of lipoproteins in an electric field based on charge and size.

Lead Question - 2013

Lipid with highest mobility is ?
a) HDL
b) LDL
c) VLDL
d) Chylomicrons

Explanation: The correct answer is a) HDL. HDL has the smallest size, highest protein content, and greatest charge density, giving it the highest electrophoretic mobility among lipoproteins. LDL, VLDL, and chylomicrons migrate more slowly because of larger size and lower density. Hence, HDL shows maximum mobility.

1) Which lipoprotein is considered the "good cholesterol"?
a) LDL
b) VLDL
c) HDL
d) Chylomicrons

Explanation: Answer: c) HDL. HDL removes cholesterol from peripheral tissues and transports it to the liver for excretion, thereby protecting against atherosclerosis. This reverse cholesterol transport is cardioprotective, unlike LDL which deposits cholesterol in arteries and increases cardiovascular risk.

2) A 55-year-old man with atherosclerosis is found to have elevated LDL. What is LDL’s major apoprotein?
a) ApoB-100
b) ApoA-I
c) ApoE
d) ApoC-II

Explanation: Answer: a) ApoB-100. LDL contains ApoB-100, which binds to LDL receptors on peripheral tissues, facilitating cholesterol delivery. Elevated LDL increases risk of plaque formation in arteries, leading to coronary artery disease.

3) Which apolipoprotein activates lipoprotein lipase?
a) ApoC-II
b) ApoE
c) ApoA-I
d) ApoB-48

Explanation: Answer: a) ApoC-II. ApoC-II acts as a cofactor for lipoprotein lipase, an enzyme that hydrolyzes triglycerides in chylomicrons and VLDL into free fatty acids, enabling their uptake into tissues for energy use or storage.

4) A patient with defective LDL receptors most likely has?
a) Tangier disease
b) Familial hypercholesterolemia
c) Abetalipoproteinemia
d) Type I hyperlipoproteinemia

Explanation: Answer: b) Familial hypercholesterolemia. It is an autosomal dominant disorder caused by defective LDL receptors, leading to high plasma LDL, xanthomas, and premature coronary artery disease due to impaired cholesterol clearance from blood.

5) Which lipoprotein transports dietary triglycerides from intestine to tissues?
a) VLDL
b) LDL
c) Chylomicrons
d) HDL

Explanation: Answer: c) Chylomicrons. Chylomicrons are synthesized in intestinal mucosa and carry dietary triglycerides and cholesterol through lymphatic circulation into blood, delivering triglycerides to tissues with the help of lipoprotein lipase.

6) A 40-year-old man has pancreatitis due to high triglycerides. Which lipoprotein is most elevated?
a) VLDL
b) HDL
c) Chylomicrons
d) LDL

Explanation: Answer: c) Chylomicrons. Severe hypertriglyceridemia due to chylomicronemia predisposes to acute pancreatitis. Elevated chylomicrons are seen in familial hyperlipoproteinemia type I due to lipoprotein lipase or ApoC-II deficiency.

7) Which apolipoprotein activates LCAT enzyme in HDL metabolism?
a) ApoA-I
b) ApoC-II
c) ApoE
d) ApoB-100

Explanation: Answer: a) ApoA-I. ApoA-I activates LCAT (lecithin cholesterol acyltransferase), which esterifies free cholesterol into cholesterol esters within HDL, aiding in reverse cholesterol transport from peripheral tissues to liver.

8) In electrophoresis, which lipoprotein migrates between β and pre-β region?
a) HDL
b) LDL
c) IDL
d) Chylomicrons

Explanation: Answer: c) IDL. Intermediate-density lipoprotein (IDL) is produced from VLDL metabolism. On electrophoresis, IDL migrates between β (LDL) and pre-β (VLDL) regions, showing intermediate properties between VLDL and LDL.

9) A 32-year-old woman has orange tonsils, very low HDL, and neuropathy. Likely diagnosis?
a) Tangier disease
b) Abetalipoproteinemia
c) Familial hypercholesterolemia
d) Type IV hyperlipidemia

Explanation: Answer: a) Tangier disease. A rare autosomal recessive disorder due to ABCA1 transporter mutation, leading to extremely low HDL, cholesterol ester storage in tissues, enlarged orange tonsils, neuropathy, and hepatosplenomegaly.

10) Which lipoprotein delivers cholesterol from peripheral tissues back to the liver?
a) LDL
b) VLDL
c) HDL
d) Chylomicrons

Explanation: Answer: c) HDL. HDL is central to reverse cholesterol transport, collecting excess cholesterol from tissues and macrophages in arterial walls, and transporting it to the liver for excretion, reducing atherosclerotic risk.

Topic: Lipoproteins
Subtopic: Cholesterol Distribution in Lipoproteins

Keyword Definitions:

• Cholesterol: A lipid molecule essential for membranes, steroid hormones, and bile salts.

• Lipoproteins: Complexes of lipids and proteins transporting lipids in plasma.

• LDL: Low-density lipoprotein, carries maximum cholesterol to tissues.

• HDL: High-density lipoprotein, involved in reverse cholesterol transport.

• VLDL: Very-low-density lipoprotein, mainly transports triglycerides.

• Chylomicrons: Lipoproteins carrying dietary triglycerides and cholesterol.

Lead Question - 2013

Maximum cholesterol is seen in?
a) VLDL
b) LDL
c) HDL
d) Chylomicrons

Explanation: LDL carries the maximum cholesterol among lipoproteins. It delivers cholesterol to peripheral tissues and contributes to atherosclerosis. HDL transports cholesterol away from tissues, while VLDL and chylomicrons are mainly triglyceride-rich particles. Correct answer is b) LDL.

1) Which apolipoprotein is the major component of LDL?
a) Apo A-I
b) Apo C-II
c) Apo B-100
d) Apo E

Explanation: Apo B-100 is the major apolipoprotein of LDL. It binds to LDL receptors on peripheral tissues, mediating cholesterol delivery. Apo A-I is for HDL, Apo C-II activates lipoprotein lipase, and Apo E is important for remnant clearance. Correct answer is c) Apo B-100.

2) A 48-year-old obese man has high LDL levels and tendon xanthomas. Which disease is most likely?
a) Abetalipoproteinemia
b) Familial hypercholesterolemia
c) Tangier disease
d) Gaucher’s disease

Explanation: Familial hypercholesterolemia is caused by mutations in the LDL receptor. It presents with high LDL, tendon xanthomas, corneal arcus, and premature coronary heart disease. Correct answer is b) Familial hypercholesterolemia.

3) Which lipoprotein is responsible for reverse cholesterol transport?
a) LDL
b) VLDL
c) HDL
d) IDL

Explanation: HDL is responsible for reverse cholesterol transport. It collects excess cholesterol from peripheral tissues and delivers it to the liver for excretion. This protects against atherosclerosis. Correct answer is c) HDL.

4) A 52-year-old diabetic with high triglycerides has elevated VLDL. What is its major lipid content?
a) Cholesterol
b) Triglycerides
c) Free fatty acids
d) Phospholipids

Explanation: VLDL is primarily triglyceride-rich, secreted by the liver to transport endogenous triglycerides to tissues. Cholesterol is a minor component. Correct answer is b) Triglycerides.

5) Which enzyme hydrolyzes triglycerides in chylomicrons and VLDL?
a) HMG-CoA reductase
b) Lipoprotein lipase
c) LCAT
d) CETP

Explanation: Lipoprotein lipase hydrolyzes triglycerides in chylomicrons and VLDL, releasing free fatty acids for uptake by tissues. It is activated by Apo C-II. Correct answer is b) Lipoprotein lipase.

6) A 45-year-old woman with metabolic syndrome shows low HDL and high LDL. Which risk is most increased?
a) Coronary heart disease
b) Osteoporosis
c) Alzheimer’s disease
d) Rheumatoid arthritis

Explanation: Dyslipidemia with high LDL and low HDL strongly increases the risk of coronary heart disease. HDL is protective, while LDL is atherogenic. Correct answer is a) Coronary heart disease.

7) Which lipoprotein delivers cholesterol from the liver to peripheral tissues?
a) HDL
b) LDL
c) Chylomicrons
d) VLDL

Explanation: LDL delivers cholesterol from the liver to peripheral tissues. Its uptake is mediated by LDL receptors. HDL does the reverse transport, while chylomicrons and VLDL mainly transport triglycerides. Correct answer is b) LDL.

8) A 50-year-old man with atherosclerosis is started on statins. What enzyme do statins inhibit?
a) Lipoprotein lipase
b) HMG-CoA reductase
c) CETP
d) LCAT

Explanation: Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. This lowers LDL cholesterol and reduces cardiovascular risk. Correct answer is b) HMG-CoA reductase.

9) Which lipoprotein transports dietary triglycerides from intestines to tissues?
a) LDL
b) HDL
c) Chylomicrons
d) VLDL

Explanation: Chylomicrons transport dietary triglycerides and cholesterol from the intestine to adipose and muscle tissues. Remnants are later cleared by the liver. Correct answer is c) Chylomicrons.

10) A 42-year-old patient has low LDL receptor activity. Which blood lipid will be elevated?
a) HDL
b) VLDL
c) LDL
d) Chylomicrons

Explanation: Defective LDL receptors cause accumulation of LDL in plasma. This is the basis of familial hypercholesterolemia, associated with xanthomas and premature coronary artery disease. Correct answer is c) LDL.

Topic: Lipoproteins
Subtopic: Role in Coronary Heart Disease

Keyword Definitions:

• Lipoproteins: Complex particles of lipids and proteins transporting cholesterol and triglycerides in plasma.

• LDL: Low-density lipoprotein, delivers cholesterol to tissues, atherogenic.

• HDL: High-density lipoprotein, removes cholesterol from tissues, protective against heart disease.

• VLDL: Very-low-density lipoprotein, carries triglycerides from liver.

• Coronary Heart Disease: Condition caused by atherosclerosis of coronary arteries.

Lead Question - 2013

Concentration of which is inversely related to the risk of coronary heart disease?
a) VLDL
b) LDL
c) HDL
d) None

Explanation: HDL concentration is inversely related to coronary heart disease risk. HDL promotes reverse cholesterol transport, removing cholesterol from peripheral tissues and macrophages, delivering it to the liver. This protects against atherosclerosis. LDL and VLDL are atherogenic. Correct answer is c) HDL.

1) Which apolipoprotein is essential for HDL function?
a) Apo B-100
b) Apo A-I
c) Apo E
d) Apo C-II

Explanation: Apo A-I is the major structural and functional apolipoprotein of HDL. It activates LCAT enzyme, enabling cholesterol esterification and reverse cholesterol transport. This function makes HDL anti-atherogenic. Correct answer is b) Apo A-I.

2) A 50-year-old man with obesity and type 2 diabetes presents with low HDL. What risk does this predispose him to?
a) Coronary heart disease
b) Hemophilia
c) Osteoporosis
d) Hypothyroidism

Explanation: Low HDL levels increase risk of coronary heart disease due to impaired reverse cholesterol transport. Diabetes, obesity, and metabolic syndrome are strongly associated with reduced HDL. Correct answer is a) Coronary heart disease.

3) Which lipoprotein is considered most atherogenic?
a) VLDL
b) HDL
c) LDL
d) IDL

Explanation: LDL is the most atherogenic lipoprotein as it deposits cholesterol in arterial walls, promoting atherosclerosis. Elevated LDL is strongly correlated with coronary artery disease. Correct answer is c) LDL.

4) A patient with Tangier disease has almost absent HDL. Which protein is defective?
a) ABCA1 transporter
b) LDL receptor
c) Apo B-100
d) HMG-CoA reductase

Explanation: Tangier disease is due to mutation in ABCA1 transporter, causing defective cholesterol efflux to Apo A-I and extremely low HDL levels. Patients present with orange tonsils and premature atherosclerosis. Correct answer is a) ABCA1 transporter.

5) Which enzyme esterifies cholesterol in HDL metabolism?
a) CETP
b) HMG-CoA reductase
c) LCAT
d) Lipoprotein lipase

Explanation: LCAT (lecithin cholesterol acyltransferase) esterifies free cholesterol in HDL, promoting maturation of HDL particles. It is activated by Apo A-I. Correct answer is c) LCAT.

6) A 45-year-old patient with high LDL and low HDL presents with xanthomas and premature coronary artery disease. Likely diagnosis?
a) Familial hypercholesterolemia
b) Abetalipoproteinemia
c) Tangier disease
d) Gaucher’s disease

Explanation: Familial hypercholesterolemia is caused by LDL receptor mutations. It presents with very high LDL, low HDL, tendon xanthomas, and premature coronary artery disease. Correct answer is a) Familial hypercholesterolemia.

7) Which lipoprotein transports dietary triglycerides?
a) Chylomicrons
b) LDL
c) HDL
d) IDL

Explanation: Chylomicrons transport dietary triglycerides from intestines to peripheral tissues. After triglyceride delivery, remnants are cleared by the liver. Correct answer is a) Chylomicrons.

8) A 60-year-old man with low HDL and smoking history develops myocardial infarction. Which mechanism explains low HDL risk?
a) Reduced cholesterol deposition
b) Impaired reverse cholesterol transport
c) Increased Apo B-100 synthesis
d) Increased LDL clearance

Explanation: Low HDL impairs reverse cholesterol transport, leading to cholesterol accumulation in arteries. This increases risk of myocardial infarction, especially in smokers. Correct answer is b) Impaired reverse cholesterol transport.

9) Which lipoprotein transfers cholesterol esters from HDL to VLDL and LDL?
a) CETP
b) LCAT
c) LPL
d) ABCA1

Explanation: CETP (cholesteryl ester transfer protein) mediates exchange of cholesterol esters from HDL to VLDL/LDL, and triglycerides in return. Correct answer is a) CETP.

10) A 55-year-old female with metabolic syndrome shows high triglycerides, low HDL, and increased cardiovascular risk. Which lipoprotein is elevated?
a) LDL
b) VLDL
c) HDL
d) Chylomicrons

Explanation: Metabolic syndrome is associated with high triglycerides due to elevated VLDL, along with low HDL. This dyslipidemia pattern strongly predisposes to cardiovascular disease. Correct answer is b) VLDL.

Topic: Lipoproteins
Subtopic: Apolipoproteins

Keyword Definitions:

• Lipoproteins: Complexes of lipids and proteins that transport fats in blood.

• Chylomicrons: Largest lipoproteins transporting dietary triglycerides from intestine.

• Apolipoproteins: Protein components of lipoproteins essential for stability and receptor binding.

• Apo B-48: Structural protein specific for chylomicrons.

• Apo B-100: Structural protein of VLDL, IDL, and LDL.

Lead Question - 2013

Major apolipoprotein of chylomicrons ?
a) B-100
b) D
c) B-48
d) None

Explanation: The major apolipoprotein of chylomicrons is Apo B-48. It is synthesized in the intestine by mRNA editing of Apo B gene. Apo B-48 provides structural integrity to chylomicrons and is essential for lipid transport from the intestine. Correct answer is c) B-48.

1) Which apolipoprotein activates lipoprotein lipase?
a) Apo C-II
b) Apo C-III
c) Apo E
d) Apo A-I

Explanation: Apo C-II is essential activator of lipoprotein lipase, facilitating triglyceride hydrolysis in chylomicrons and VLDL. Apo C-III inhibits lipoprotein lipase. Apo E helps in remnant clearance. Apo A-I activates LCAT. Correct answer is a) Apo C-II.

2) A 2-year-old child presents with recurrent pancreatitis and milky plasma. Which apolipoprotein deficiency is likely?
a) Apo C-II
b) Apo A-I
c) Apo B-100
d) Apo E

Explanation: Deficiency of Apo C-II leads to defective activation of lipoprotein lipase, causing familial chylomicronemia. This presents with pancreatitis, eruptive xanthomas, and creamy plasma. Apo A-I deficiency affects HDL, Apo B-100 deficiency LDL, Apo E remnant clearance. Correct answer is a) Apo C-II.

3) Which apolipoprotein is necessary for binding LDL to its receptor?
a) Apo B-48
b) Apo C-II
c) Apo B-100
d) Apo A-I

Explanation: Apo B-100 is the ligand for LDL receptors, essential for LDL uptake into cells. Apo B-48 does not bind LDL receptors. Apo A-I activates LCAT, and Apo C-II activates lipoprotein lipase. Correct answer is c) Apo B-100.

4) A patient with type III hyperlipoproteinemia has defect in which apolipoprotein?
a) Apo A-I
b) Apo C-II
c) Apo E
d) Apo B-48

Explanation: Type III hyperlipoproteinemia is caused by Apo E deficiency, leading to defective clearance of chylomicron and VLDL remnants. This condition results in premature atherosclerosis and palmar xanthomas. Correct answer is c) Apo E.

5) Which apolipoprotein activates LCAT enzyme in HDL metabolism?
a) Apo B-100
b) Apo A-I
c) Apo E
d) Apo C-II

Explanation: Apo A-I is the activator of lecithin-cholesterol acyltransferase (LCAT), facilitating cholesterol esterification in HDL particles. This reaction is crucial for reverse cholesterol transport. Correct answer is b) Apo A-I.

6) A neonate presents with failure to thrive and fat malabsorption. Genetic testing reveals absence of Apo B. Which disorder is this?
a) Abetalipoproteinemia
b) Hypoalphalipoproteinemia
c) Tangier disease
d) Familial hypercholesterolemia

Explanation: Abetalipoproteinemia is caused by deficiency of Apo B-containing lipoproteins (Apo B-48 and Apo B-100). It leads to fat malabsorption, acanthocytosis, and fat-soluble vitamin deficiencies. Correct answer is a) Abetalipoproteinemia.

7) Which apolipoprotein is present in HDL and promotes cholesterol efflux from cells?
a) Apo E
b) Apo C-II
c) Apo A-I
d) Apo B-48

Explanation: Apo A-I, the major protein of HDL, promotes cholesterol efflux via interaction with ABCA1 transporter and activates LCAT. This makes it anti-atherogenic. Correct answer is c) Apo A-I.

8) A patient with recurrent premature atherosclerosis has high Lp(a). Which apolipoprotein characterizes Lp(a)?
a) Apo B-48
b) Apo C-II
c) Apo A-I
d) Apo(a)

Explanation: Lipoprotein (a) consists of LDL particle attached to Apo(a), which resembles plasminogen. Elevated Lp(a) increases risk of atherosclerosis and thrombosis. Correct answer is d) Apo(a).

9) Which apolipoprotein inhibits lipoprotein lipase activity?
a) Apo C-II
b) Apo C-III
c) Apo A-I
d) Apo B-100

Explanation: Apo C-III inhibits lipoprotein lipase, thereby slowing triglyceride clearance from plasma. In contrast, Apo C-II activates the enzyme. Correct answer is b) Apo C-III.

10) A patient develops defective clearance of IDL remnants. Which apolipoprotein interaction is defective?
a) Apo B-100 with LDL receptor
b) Apo A-I with ABCA1
c) Apo E with remnant receptor
d) Apo C-II with LPL

Explanation: Clearance of IDL and chylomicron remnants requires Apo E binding to remnant receptors. Apo E deficiency causes remnant accumulation and type III hyperlipoproteinemia. Correct answer is c) Apo E.

Topic: Lipid Metabolism
Subtopic: Low-Density Lipoproteins (LDL)

Keyword Definitions

• LDL – Low-density lipoproteins carry cholesterol from liver to tissues; often called “bad cholesterol.”

• Chylomicrons – Largest lipoproteins transporting dietary triglycerides from intestine.

• VLDL – Very low-density lipoproteins transport endogenous triglycerides from liver.

• Cholesterol – Steroid lipid essential for membranes, hormones, bile acids; excess causes atherosclerosis.

• Atherosclerosis – Hardening of arteries due to lipid deposition and plaque formation.

Lead Question - 2013

All are true about LDL except ?
a) More dense than chylomicron
b) Smaller than VLDL
c) Transports maximum amount of lipid
d) Contains maximum cholesterol

Explanation: The correct answer is c) Transports maximum amount of lipid. LDL is denser than chylomicrons and smaller than VLDL, containing the maximum cholesterol fraction, not triglycerides. Chylomicrons transport the maximum lipid content. LDL is atherogenic, delivering cholesterol to peripheral tissues and contributing to cardiovascular risk when elevated in circulation.

1) Which apolipoprotein is essential for LDL receptor recognition?
a) Apo A-I
b) Apo B-100
c) Apo E
d) Apo C-II

Explanation: The correct answer is b) Apo B-100. Apo B-100 is the structural protein of LDL and mediates binding to the LDL receptor for endocytosis. Apo A-I activates LCAT, Apo C-II activates lipoprotein lipase, and Apo E helps remnant uptake. Thus, Apo B-100 is critical for LDL metabolism.

2) Elevated LDL cholesterol is most strongly associated with which condition?
a) Atherosclerosis
b) Hemophilia
c) Nephrolithiasis
d) Anemia

Explanation: The correct answer is a) Atherosclerosis. High LDL levels promote cholesterol deposition in arterial walls, forming plaques that narrow arteries and predispose to myocardial infarction and stroke. Hemophilia, nephrolithiasis, and anemia are unrelated. Therefore, LDL cholesterol is a major target in cardiovascular risk reduction strategies using diet and statins.

3) A 45-year-old male with xanthomas has very high LDL cholesterol. The most likely genetic disorder is ?
a) Familial hypercholesterolemia
b) Abetalipoproteinemia
c) Tangier disease
d) Familial chylomicronemia

Explanation: The correct answer is a) Familial hypercholesterolemia. This autosomal dominant disorder results from LDL receptor mutations, causing defective clearance of LDL from plasma. Patients develop tendon xanthomas, arcus cornealis, and premature atherosclerosis. Abetalipoproteinemia and Tangier disease involve apo deficiencies, while familial chylomicronemia is linked with hypertriglyceridemia.

4) Which enzyme regulates cholesterol synthesis and is inhibited by statins?
a) HMG-CoA reductase
b) Lipoprotein lipase
c) LCAT
d) CETP

Explanation: The correct answer is a) HMG-CoA reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, the rate-limiting step in cholesterol synthesis. Statins inhibit it, lowering endogenous cholesterol production and increasing LDL receptor expression, thus reducing LDL cholesterol levels and risk of cardiovascular disease. Other enzymes act in lipoprotein metabolism.

5) A patient with nephrotic syndrome shows elevated LDL cholesterol. The mechanism is ?
a) Increased hepatic synthesis
b) Reduced lipolysis
c) Increased intestinal absorption
d) Reduced clearance of HDL

Explanation: The correct answer is a) Increased hepatic synthesis. In nephrotic syndrome, loss of albumin in urine stimulates hepatic protein synthesis, including lipoproteins, leading to elevated LDL cholesterol. Reduced clearance of HDL is not seen. This dyslipidemia contributes to increased cardiovascular risk in patients with nephrotic syndrome.

6) Which lipoprotein is anti-atherogenic and protects against LDL cholesterol?
a) HDL
b) VLDL
c) IDL
d) Chylomicron

Explanation: The correct answer is a) HDL. HDL mediates reverse cholesterol transport, carrying cholesterol from peripheral tissues to the liver for excretion. High HDL levels reduce atherosclerotic risk, balancing the harmful effects of LDL. VLDL and IDL are triglyceride-rich, while chylomicrons transport dietary fat, none of which have protective effects.

7) A 52-year-old diabetic patient with metabolic syndrome has elevated small dense LDL particles. Why are they more atherogenic?
a) Higher cholesterol content
b) Greater endothelial penetration
c) Reduced Apo B
d) Increased receptor clearance

Explanation: The correct answer is b) Greater endothelial penetration. Small dense LDL particles more easily penetrate the vascular endothelium and are more prone to oxidation, making them more atherogenic than large LDL. They are associated with insulin resistance and cardiovascular disease. Their clearance is not increased; instead, they persist longer in circulation.

8) Which drug binds bile acids and lowers LDL cholesterol?
a) Cholestyramine
b) Niacin
c) Fibrates
d) Ezetimibe

Explanation: The correct answer is a) Cholestyramine. Bile acid sequestrants like cholestyramine bind bile acids in the intestine, preventing reabsorption and forcing the liver to use cholesterol to synthesize new bile acids. This increases LDL receptor expression and lowers LDL cholesterol. Niacin and fibrates mainly affect triglycerides, while ezetimibe inhibits cholesterol absorption.

9) A 38-year-old woman with premature coronary artery disease shows elevated Lp(a). This abnormal lipoprotein resembles ?
a) LDL
b) VLDL
c) HDL
d) Chylomicron

Explanation: The correct answer is a) LDL. Lipoprotein(a) is structurally similar to LDL but has an additional apolipoprotein(a), which interferes with fibrinolysis, increasing thrombotic and atherosclerotic risk. Its elevation is genetically determined and is a strong independent cardiovascular risk factor. VLDL, HDL, and chylomicrons lack this unique apoprotein.

10) Which test is most useful for assessing cardiovascular risk related to LDL?
a) LDL-C measurement
b) HDL-C measurement
c) Total cholesterol measurement
d) Triglyceride measurement

Explanation: The correct answer is a) LDL-C measurement. LDL cholesterol level is the primary target for cardiovascular risk assessment and management. Although total cholesterol and HDL are important, LDL-C is directly linked to atherogenesis. Triglycerides influence VLDL metabolism but are not as strongly associated with cardiovascular risk as LDL cholesterol.

Topic: Lipid Metabolism
Subtopic: Lipoproteins

Keyword Definitions

• Lipoproteins – Complexes of lipids and proteins that transport hydrophobic lipids in blood.

• Chylomicrons – Lipoproteins carrying dietary triglycerides from intestine to tissues.

• VLDL – Very low-density lipoproteins carrying endogenous triglycerides from liver.

• LDL – Low-density lipoproteins transporting cholesterol to peripheral tissues.

• Lp(a) – Abnormal lipoprotein associated with increased risk of atherosclerosis.

Lead Question - 2013

Which is an abnormal lipoprotein ?
a) VLDL
b) Chylomicron
c) Lp (a)
d) LDL

Explanation: The correct answer is c) Lp(a). Lipoprotein(a) is considered an abnormal lipoprotein, structurally similar to LDL but with an additional apolipoprotein(a). It interferes with fibrinolysis and promotes atherogenesis. VLDL, LDL, and chylomicrons are normal physiological lipoproteins essential for lipid transport and metabolism in humans.

1) The major apolipoprotein of chylomicrons is ?
a) Apo C
b) Apo A
c) Apo B-48
d) Apo E

Explanation: The correct answer is c) Apo B-48. Chylomicrons are lipoproteins synthesized in the intestine for dietary lipid transport. Apo B-48 is their structural apolipoprotein. Apo C and Apo E are acquired from HDL in circulation and play roles in metabolism, but Apo B-48 is essential for chylomicron formation.

2) Which enzyme hydrolyzes triglycerides in chylomicrons and VLDL?
a) Lipoprotein lipase
b) Hepatic lipase
c) Hormone-sensitive lipase
d) Pancreatic lipase

Explanation: The correct answer is a) Lipoprotein lipase. This enzyme, located on endothelial cells of capillaries in adipose tissue, heart, and skeletal muscle, hydrolyzes triglycerides from chylomicrons and VLDL into free fatty acids and glycerol. Hormone-sensitive lipase acts inside adipocytes, while hepatic lipase acts on IDL and HDL particles.

3) A 40-year-old male presents with xanthomas and early coronary artery disease. Which abnormal lipoprotein is most implicated?
a) Lp(a)
b) HDL
c) LDL
d) Chylomicron

Explanation: The correct answer is a) Lp(a). Elevated lipoprotein(a) levels are strongly associated with premature atherosclerosis. It resembles LDL but contains apolipoprotein(a), which inhibits fibrinolysis. LDL elevation also contributes, but Lp(a) is specifically abnormal and highly atherogenic. HDL is protective, while chylomicrons are not implicated in atherosclerosis.

4) Which lipoprotein is synthesized in the intestine?
a) Chylomicron
b) VLDL
c) LDL
d) HDL

Explanation: The correct answer is a) Chylomicron. Chylomicrons are produced in intestinal enterocytes to transport dietary triglycerides and cholesterol through the lymphatic system into blood circulation. VLDL and LDL are synthesized by the liver, while HDL is synthesized both in liver and intestine. Intestinal synthesis is a key step for dietary fat absorption.

5) Familial hypercholesterolemia is caused by mutation in which receptor?
a) LDL receptor
b) VLDL receptor
c) HDL receptor
d) Scavenger receptor

Explanation: The correct answer is a) LDL receptor. Familial hypercholesterolemia is an autosomal dominant disorder characterized by defective LDL receptor function, leading to high plasma LDL levels and premature atherosclerosis. VLDL and HDL receptors are not implicated. Scavenger receptors are involved in uptake of oxidized LDL by macrophages in atherosclerotic plaques.

6) A patient presents with pancreatitis and eruptive xanthomas. Labs show high triglycerides. The most likely lipoprotein elevated is ?
a) VLDL
b) LDL
c) HDL
d) Chylomicron

Explanation: The correct answer is d) Chylomicron. Severe hypertriglyceridemia due to chylomicronemia is associated with acute pancreatitis and eruptive xanthomas. VLDL elevation can also cause hypertriglyceridemia but is less dramatic. LDL elevation leads to atherosclerosis, while HDL is protective. Identifying chylomicron elevation is critical for treatment and prevention of recurrent pancreatitis.

7) Which apolipoprotein activates LCAT (lecithin cholesterol acyl transferase)?
a) Apo A-I
b) Apo B-100
c) Apo C-II
d) Apo E

Explanation: The correct answer is a) Apo A-I. Apo A-I, the major structural apolipoprotein of HDL, activates LCAT, an enzyme essential for cholesterol esterification during reverse cholesterol transport. Apo C-II activates lipoprotein lipase, Apo E mediates remnant uptake, and Apo B-100 is a structural apolipoprotein of VLDL and LDL.

8) A patient with nephrotic syndrome has increased risk of atherosclerosis due to elevated ?
a) HDL
b) LDL
c) VLDL
d) Chylomicron

Explanation: The correct answer is b) LDL. In nephrotic syndrome, loss of proteins in urine stimulates hepatic lipoprotein synthesis, leading to elevated LDL cholesterol and increased atherosclerotic risk. HDL is reduced, worsening the risk. VLDL and chylomicrons may rise, but LDL elevation is the primary contributor to cardiovascular disease in these patients.

9) Which lipoprotein is considered anti-atherogenic?
a) HDL
b) LDL
c) VLDL
d) Chylomicron

Explanation: The correct answer is a) HDL. High-density lipoprotein promotes reverse cholesterol transport, removing excess cholesterol from peripheral tissues and delivering it to the liver for excretion. It is protective against cardiovascular disease. LDL and VLDL are atherogenic, while chylomicrons transport dietary lipids and do not directly protect against atherosclerosis.

10) A 55-year-old male with myocardial infarction is found to have elevated Lp(a). This abnormal lipoprotein increases risk by interfering with ?
a) Fibrinolysis
b) Lipolysis
c) Cholesterol synthesis
d) Bile acid formation

Explanation: The correct answer is a) Fibrinolysis. Lipoprotein(a) is structurally similar to plasminogen and competes with it, inhibiting fibrinolysis. This promotes thrombosis in addition to atherogenesis, markedly increasing cardiovascular risk. Lipolysis, cholesterol synthesis, and bile acid formation are not directly inhibited by Lp(a). Its presence is a major cardiovascular risk factor.

Topic: Inborn Errors of Metabolism
Subtopic: Sphingolipidoses

Keyword Definitions:

• Sphingolipidoses: A group of inherited metabolic disorders due to defective lysosomal enzymes leading to accumulation of sphingolipids.

• Krabbe’s disease: A lysosomal storage disorder caused by deficiency of β-galactocerebrosidase, leading to accumulation of psychosine and severe neurodegeneration.

• Sphingomyelinase: Enzyme deficient in Niemann-Pick disease, causing sphingomyelin accumulation.

• Hexosaminidase A: Enzyme deficient in Tay-Sachs disease, leading to GM2 ganglioside accumulation.

• Arylsulfatase A: Enzyme deficient in Metachromatic leukodystrophy, leading to sulfatide accumulation.

• Psychosine: A toxic metabolite accumulating in Krabbe’s disease, responsible for oligodendrocyte destruction and demyelination.

Lead Question - 2013

Krabbes disease is due to deficiency of ?

a) Sphingomyelinase
b) Beta galactocerebrosidase
c) Hexosaminidase
d) Arylsulfatase

Explanation: The correct answer is Beta galactocerebrosidase. Krabbe’s disease is a rare autosomal recessive lysosomal storage disorder. Deficiency of β-galactocerebrosidase causes accumulation of psychosine, leading to oligodendrocyte destruction and severe demyelination. Symptoms include irritability, developmental delay, optic atrophy, seizures, and spasticity. Other enzyme deficiencies cause distinct sphingolipidoses.

1) Which enzyme deficiency causes Niemann-Pick disease?
a) Hexosaminidase A
b) Arylsulfatase A
c) Sphingomyelinase
d) β-galactocerebrosidase
Explanation: The correct answer is Sphingomyelinase. Niemann-Pick disease results from sphingomyelinase deficiency leading to sphingomyelin accumulation in macrophages ("foamy cells"). It presents with hepatosplenomegaly, neurodegeneration, and cherry-red spot in retina. This differentiates it from Tay-Sachs, which also shows cherry-red spot but without hepatosplenomegaly.

2) A 6-month-old presents with progressive neurodegeneration, exaggerated startle response, and cherry-red macula. Likely enzyme deficiency?
a) Hexosaminidase A
b) Arylsulfatase A
c) β-galactocerebrosidase
d) Glucocerebrosidase
Explanation: The correct answer is Hexosaminidase A. This enzyme deficiency causes Tay-Sachs disease, characterized by GM2 ganglioside accumulation. Clinical features include neurodegeneration, developmental delay, cherry-red macula, and exaggerated startle reflex. No hepatosplenomegaly is seen, which differentiates it from Niemann-Pick disease.

3) Which enzyme deficiency is responsible for Gaucher’s disease?
a) Glucocerebrosidase
b) Arylsulfatase A
c) Hexosaminidase A
d) Sphingomyelinase
Explanation: The correct answer is Glucocerebrosidase. Gaucher’s disease is due to deficiency of glucocerebrosidase, leading to accumulation of glucocerebroside. It presents with hepatosplenomegaly, bone pain, and cytopenias. Pathology shows Gaucher cells—lipid-laden macrophages with "crumpled tissue paper" cytoplasm.

4) A child with Krabbe’s disease typically shows which neuropathological finding?
a) Gaucher cells
b) Globoid cells
c) Foam cells
d) Onion bulb neuropathy
Explanation: The correct answer is Globoid cells. Krabbe’s disease features multinucleated globoid cells, which are pathognomonic. They result from accumulation of psychosine due to β-galactocerebrosidase deficiency. These cells cause widespread demyelination, severe neurodegeneration, and progressive neurological decline in infancy.

5) Which of the following is deficient in Metachromatic leukodystrophy?
a) Arylsulfatase A
b) Glucocerebrosidase
c) β-galactocerebrosidase
d) Hexosaminidase A
Explanation: The correct answer is Arylsulfatase A. Metachromatic leukodystrophy results from arylsulfatase A deficiency, leading to sulfatide accumulation. This causes progressive central and peripheral demyelination, ataxia, and dementia. It is differentiated from Krabbe’s disease by its enzyme defect and slower progression.

6) A 2-year-old presents with hepatosplenomegaly, bone crises, and anemia. Bone marrow shows "crumpled tissue paper" macrophages. Likely diagnosis?
a) Gaucher’s disease
b) Niemann-Pick disease
c) Krabbe’s disease
d) Fabry’s disease
Explanation: The correct answer is Gaucher’s disease. Glucocerebrosidase deficiency causes glucocerebroside accumulation in macrophages, producing characteristic "crumpled tissue paper" cytoplasm. Clinical features include hepatosplenomegaly, pancytopenia, and bone pain. This is the most common lysosomal storage disorder.

7) Which clinical feature is most characteristic of Krabbe’s disease?
a) Hepatosplenomegaly
b) Optic atrophy
c) Bone crises
d) Angiokeratomas
Explanation: The correct answer is Optic atrophy. Krabbe’s disease manifests with irritability, developmental delay, spasticity, seizures, and optic atrophy due to severe demyelination. Unlike Gaucher’s and Niemann-Pick, hepatosplenomegaly is absent. Angiokeratomas are seen in Fabry’s disease.

8) Which genetic inheritance pattern do sphingolipidoses usually follow?
a) Autosomal recessive
b) Autosomal dominant
c) X-linked dominant
d) X-linked recessive
Explanation: The correct answer is Autosomal recessive. Most sphingolipidoses, including Krabbe’s, Tay-Sachs, Niemann-Pick, and Gaucher’s disease, follow autosomal recessive inheritance. An important exception is Fabry’s disease, which is X-linked recessive. Recognizing inheritance helps in genetic counseling and risk prediction in affected families.

9) Fabry’s disease is due to deficiency of?
a) α-galactosidase A
b) β-galactocerebrosidase
c) Glucocerebrosidase
d) Arylsulfatase A
Explanation: The correct answer is α-galactosidase A. Fabry’s disease, an X-linked recessive disorder, results from α-galactosidase A deficiency, leading to ceramide trihexoside accumulation. Clinical features include angiokeratomas, peripheral neuropathy, hypohidrosis, and progressive renal and cardiac disease. Unlike Krabbe’s disease, it does not present with demyelination.

10) A 9-month-old with Krabbe’s disease presents with developmental regression and seizures. Which metabolite accumulates?
a) Psychosine
b) Glucosylceramide
c) GM2 ganglioside
d) Sphingomyelin
Explanation: The correct answer is Psychosine. In Krabbe’s disease, β-galactocerebrosidase deficiency leads to accumulation of psychosine, a toxic metabolite. Psychosine causes destruction of oligodendrocytes and Schwann cells, leading to widespread demyelination. Other listed metabolites accumulate in different sphingolipidoses.

Topic: Metabolism
Subtopic: Fatty Acid Oxidation

Keyword Definitions:

• Fatty acid oxidation: The breakdown of fatty acids in mitochondria to generate acetyl-CoA, NADH, and FADH2 for energy.

• Carnitine: A carrier molecule essential for the transport of long-chain fatty acids across the mitochondrial inner membrane.

• Creatine: A compound used to store and release energy in muscle cells.

• Creatinine: A waste product of creatine metabolism, excreted in urine.

• Mitochondrial membrane: The double-layered structure regulating entry and exit of metabolites for energy metabolism.

• β-oxidation: The catabolic process where fatty acids are broken down into acetyl-CoA units in mitochondria.

Lead Question - 2013

What is essential for transfer of fatty acid across mitochondrial membrane -

a) Creatine
b) Creatinine
c) Carnitine
d) None

Explanation: The correct answer is Carnitine. Long-chain fatty acids cannot directly cross the mitochondrial membrane. Carnitine shuttles them as acyl-carnitine complexes into mitochondria for β-oxidation. Creatine stores high-energy phosphate, creatinine is a waste product, and neither are involved in fatty acid transport. Carnitine deficiency leads to hypoglycemia and muscle weakness.

1) Which enzyme catalyzes the conversion of acyl-CoA to acyl-carnitine?
a) CPT-I
b) CPT-II
c) Acyl-CoA dehydrogenase
d) Carnitine acetyltransferase
Explanation: The correct answer is CPT-I (Carnitine Palmitoyltransferase-I). Located on the outer mitochondrial membrane, it converts fatty acyl-CoA into fatty acyl-carnitine, which can cross into mitochondria. CPT-II reconverts acyl-carnitine to acyl-CoA inside mitochondria. Acyl-CoA dehydrogenase acts in β-oxidation, not transport.

2) A newborn with hypoketotic hypoglycemia, hepatomegaly, and muscle weakness is most likely deficient in?
a) Carnitine
b) CPT-I
c) CPT-II
d) Glucose-6-phosphatase
Explanation: The correct answer is Carnitine. Carnitine deficiency prevents transport of long-chain fatty acids into mitochondria, leading to impaired β-oxidation, low ketone body production, hypoglycemia, and hepatomegaly. CPT-I and CPT-II deficiencies produce similar syndromes, but primary systemic carnitine deficiency is classic. Glucose-6-phosphatase deficiency causes glycogen storage disease type I, not fatty acid oxidation defect.

3) Which fatty acids can enter mitochondria without carnitine shuttle?
a) Long-chain fatty acids
b) Medium-chain fatty acids
c) Very-long-chain fatty acids
d) None
Explanation: The correct answer is Medium-chain fatty acids. Medium-chain fatty acids (C6–C12) can diffuse freely across mitochondrial membranes without requiring the carnitine shuttle. Long-chain fatty acids (C14–C20) require carnitine. Very-long-chain fatty acids are oxidized in peroxisomes first. This explains why medium-chain triglyceride (MCT) oils bypass carnitine dependency.

4) A 2-year-old with recurrent hypoglycemia during fasting, seizures, and no ketone bodies is most likely suffering from?
a) Medium-chain acyl-CoA dehydrogenase deficiency
b) CPT-II deficiency
c) Pyruvate dehydrogenase deficiency
d) Von Gierke’s disease
Explanation: The correct answer is MCAD deficiency. Medium-chain acyl-CoA dehydrogenase deficiency blocks β-oxidation of medium-chain fatty acids, leading to hypoketotic hypoglycemia and seizures during fasting. CPT-II deficiency affects muscle during prolonged exercise. Pyruvate dehydrogenase deficiency affects carbohydrate metabolism. Von Gierke’s disease involves glycogen storage defect, not fatty acid oxidation.

5) Which transport system is inhibited by malonyl-CoA?
a) CPT-I
b) CPT-II
c) Adenine nucleotide translocase
d) Citrate transporter
Explanation: The correct answer is CPT-I. Malonyl-CoA, the first committed intermediate in fatty acid synthesis, inhibits CPT-I to prevent simultaneous fatty acid oxidation and synthesis. This regulation ensures metabolic balance between storage and utilization of fatty acids. CPT-II, adenine nucleotide translocase, and citrate transporter are not inhibited by malonyl-CoA.

6) A patient develops myoglobinuria after prolonged exercise with fasting. Carnitine levels are normal. Likely defect?
a) CPT-I deficiency
b) CPT-II deficiency
c) MCAD deficiency
d) Pyruvate carboxylase deficiency
Explanation: The correct answer is CPT-II deficiency. Carnitine is normal, but CPT-II deficiency prevents reconversion of acyl-carnitine to acyl-CoA inside mitochondria, impairing fatty acid oxidation. This leads to exercise-induced muscle pain and myoglobinuria. CPT-I deficiency affects liver metabolism. MCAD deficiency causes fasting hypoglycemia. Pyruvate carboxylase deficiency affects gluconeogenesis.

7) Where in the cell does β-oxidation of fatty acids occur?
a) Cytoplasm
b) Peroxisome
c) Mitochondrial matrix
d) Endoplasmic reticulum
Explanation: The correct answer is Mitochondrial matrix. The carnitine shuttle delivers long-chain fatty acids into the mitochondrial matrix, where β-oxidation enzymes sequentially shorten fatty acyl-CoA to generate acetyl-CoA. Peroxisomes handle very-long-chain fatty acids. Cytoplasm is the site of fatty acid synthesis, not oxidation. Endoplasmic reticulum handles lipid synthesis and desaturation.

8) A 30-year-old man collapses after fasting and strenuous exercise. Labs show hypoglycemia, absent ketones, and dicarboxylic aciduria. Likely diagnosis?
a) CPT-I deficiency
b) CPT-II deficiency
c) MCAD deficiency
d) Primary carnitine deficiency
Explanation: The correct answer is MCAD deficiency. Medium-chain acyl-CoA dehydrogenase deficiency blocks oxidation of medium-chain fatty acids, leading to hypoketotic hypoglycemia and dicarboxylic aciduria. CPT deficiencies usually show ketones but impaired fatty acid transport. Carnitine deficiency prevents transport but does not specifically cause dicarboxylic aciduria, which is typical of MCAD deficiency.

9) Which molecule is directly produced by each round of β-oxidation?
a) NADPH
b) Acetyl-CoA
c) Citrate
d) Lactate
Explanation: The correct answer is Acetyl-CoA. Each cycle of β-oxidation removes two carbons as acetyl-CoA while producing NADH and FADH2. Acetyl-CoA enters the TCA cycle or serves as a substrate for ketone body synthesis. NADPH is produced in the pentose phosphate pathway, not fatty acid oxidation. Lactate and citrate are unrelated here.

10) A 6-month-old with seizures, hypotonia, hepatomegaly, and hypoketotic hypoglycemia is suspected of fatty acid oxidation defect. Which lab test confirms carnitine deficiency?
a) Plasma acylcarnitine profile
b) Serum creatinine
c) Liver biopsy
d) Urinary ketone levels
Explanation: The correct answer is Plasma acylcarnitine profile. Measurement of plasma acylcarnitine detects abnormal fatty acid transport and confirms carnitine deficiency. Serum creatinine assesses kidney function, not fatty acid metabolism. Liver biopsy may show steatosis but is nonspecific. Urinary ketones only indicate ketosis, not carnitine deficiency.

Topic: Metabolism
Subtopic: Ketone Body Metabolism

Keyword Definitions:

• Ketone bodies: Water-soluble molecules produced in liver mitochondria during fatty acid oxidation.

• Glycosuria: Excretion of glucose in urine, usually due to diabetes mellitus.

• Starvation: Condition where prolonged fasting leads to fat breakdown and ketone body formation.

• Obesity: Excessive fat accumulation affecting metabolism and health.

• Diabetes mellitus: Disorder of glucose metabolism with hyperglycemia and possible ketonuria.

• Diabetes insipidus: Disorder characterized by excessive thirst and dilute urine, unrelated to glucose.

Lead Question - 2013

Ketone body formation without glycosuria is seen in ?

a) Diabetes mellitus
b) Diabetes insipidus
c) Starvation
d) Obesity

Explanation: The correct answer is Starvation. In starvation, ketone bodies form due to fat oxidation without glycosuria, as blood glucose is low. In diabetes mellitus, ketone bodies occur with glycosuria. Diabetes insipidus involves water balance, not ketones. Obesity may increase fat metabolism but not necessarily ketone formation. Starvation uniquely causes ketosis without glycosuria.

1) Which ketone body is the major fuel for the brain during prolonged fasting?
a) Acetoacetate
b) β-hydroxybutyrate
c) Acetone
d) Pyruvate
Explanation: The correct answer is β-hydroxybutyrate. During prolonged starvation, β-hydroxybutyrate becomes the main energy source for the brain, sparing glucose. Acetone is exhaled, acetoacetate is used but less dominant, and pyruvate is not a ketone. This metabolic adaptation preserves muscle protein and maintains brain function effectively.

2) A 5-year-old child with vomiting and hypoglycemia after fasting shows elevated ketones but no glycosuria. Likely cause?
a) Glycogen storage disease
b) Starvation ketosis
c) Diabetes mellitus
d) Galactosemia
Explanation: The correct answer is Starvation ketosis. Children have limited glycogen stores and rapidly switch to fat metabolism during fasting. This leads to ketone formation without glycosuria. Diabetes mellitus produces glycosuria, galactosemia involves galactose, and glycogen storage disease shows hypoglycemia but may not show ketosis without fasting stress.

3) Which enzyme is responsible for the conversion of HMG-CoA to acetoacetate?
a) HMG-CoA lyase
b) HMG-CoA reductase
c) Thiolase
d) Succinyl-CoA transferase
Explanation: The correct answer is HMG-CoA lyase. This enzyme cleaves HMG-CoA to form acetoacetate, a primary ketone body. HMG-CoA reductase functions in cholesterol synthesis. Thiolase is involved in fatty acid breakdown. Succinyl-CoA transferase helps utilize ketones in extrahepatic tissues, not in their synthesis in the liver mitochondria.

4) A 25-year-old man fasting for 48 hours shows fruity odor breath. Which compound is responsible?
a) Acetone
b) Acetoacetate
c) β-hydroxybutyrate
d) Ethanol
Explanation: The correct answer is Acetone. During prolonged fasting or diabetic ketoacidosis, excess acetoacetate decarboxylates spontaneously to acetone, giving fruity odor breath. Acetoacetate and β-hydroxybutyrate are metabolically active but odorless. Ethanol causes alcohol odor. Thus, acetone in exhaled air is diagnostic of ketosis in fasting or diabetes.

5) Which tissue cannot utilize ketone bodies due to absence of succinyl-CoA transferase?
a) Muscle
b) Brain
c) Kidney
d) Liver
Explanation: The correct answer is Liver. Although the liver synthesizes ketone bodies, it lacks succinyl-CoA transferase (thiophorase) required for ketone body utilization. Hence, ketone bodies are released into circulation for use by other tissues like muscle, brain during fasting, and kidney. This ensures hepatic ketone bodies serve as fuel for extrahepatic tissues.

6) A diabetic patient with high ketones but no glycosuria is most likely suffering from?
a) Type 1 diabetes
b) Type 2 diabetes
c) Starvation ketosis
d) Renal glucosuria
Explanation: The correct answer is Starvation ketosis. In diabetes, ketones usually accompany glycosuria due to high glucose. If ketones exist without glycosuria, starvation ketosis is more likely. Renal glucosuria shows glycosuria without ketosis. This clinical distinction helps differentiate metabolic states and manage treatment appropriately in patients with suspected diabetes or fasting-induced changes.

7) Which ketone body is exhaled in breath?
a) Acetoacetate
b) β-hydroxybutyrate
c) Acetone
d) Citrate
Explanation: The correct answer is Acetone. Acetone is volatile and eliminated via breath and urine. Acetoacetate and β-hydroxybutyrate are actively metabolized in tissues for energy. Citrate is an intermediate of the TCA cycle, not a ketone body. Clinical detection of fruity odor breath indicates acetone, commonly found in starvation and diabetic ketoacidosis patients.

8) A 10-year-old boy presents with dehydration, vomiting, fruity odor breath but no glucose in urine. Diagnosis?
a) Diabetic ketoacidosis
b) Starvation ketosis
c) Renal failure
d) Alcohol intoxication
Explanation: The correct answer is Starvation ketosis. Absence of glycosuria with ketosis favors starvation over diabetes. In diabetic ketoacidosis, glucose is elevated with glycosuria. Renal failure does not typically cause ketosis. Alcohol intoxication produces different metabolic acidosis. Thus, in children, starvation quickly induces ketosis without glycosuria, explaining the presentation effectively.

9) Which of the following is not a true ketone body?
a) Acetone
b) Acetoacetate
c) β-hydroxybutyrate
d) Oxaloacetate
Explanation: The correct answer is Oxaloacetate. Ketone bodies include acetoacetate, β-hydroxybutyrate, and acetone. Oxaloacetate is an intermediate of the TCA cycle, not a ketone. It plays a role in gluconeogenesis and energy metabolism. The distinction is important for understanding energy sources during fasting and pathological conditions like diabetic ketoacidosis and prolonged starvation in humans.

10) A patient on prolonged fasting shows normal glucose, elevated ketones, no glycosuria. Which is true?
a) Glucose maintained by gluconeogenesis
b) Glycogenolysis still ongoing
c) Ketones formed due to amino acid oxidation
d) Ketones used by liver
Explanation: The correct answer is Glucose maintained by gluconeogenesis. In prolonged fasting, hepatic gluconeogenesis maintains blood glucose while fat breakdown produces ketones for energy. Glycogen stores deplete early, and ketones arise mainly from fatty acids, not amino acids. The liver cannot utilize ketones, only extrahepatic tissues can.

Topic: Lipid Metabolism | Subtopic: Ketone Body Utilization

Keyword Definitions:

• Ketone bodies: Water-soluble molecules (acetoacetate, β-hydroxybutyrate, acetone) produced from fatty acid oxidation in liver mitochondria.

• Thiophorase: Key enzyme needed for ketone utilization; absent in the liver.

• RBC: Red blood cells lack mitochondria and cannot utilize ketone bodies.

• Brain: Can use ketone bodies during prolonged fasting as an alternate fuel.

Lead Question - 2013

Ketone bodies are not used by ?

a) Muscle
b) Brain
c) RBC
d) Renal cortex

Explanation: The correct answer is c) RBC. Red blood cells lack mitochondria, which are essential for ketone oxidation, so they cannot utilize ketone bodies. Muscle, renal cortex, and brain (during fasting) can use ketones as alternate fuel. Thus, RBCs rely exclusively on glycolysis for ATP generation. (50 words)

1. Which enzyme is absent in liver, preventing ketone body utilization?

a) Thiophorase
b) HMG CoA synthase
c) HMG CoA lyase
d) Pyruvate carboxylase

Explanation: The answer is a) Thiophorase. Liver synthesizes ketone bodies but cannot utilize them due to the absence of thiophorase, the enzyme required for conversion of acetoacetate to acetoacetyl-CoA. This ensures that ketone bodies are spared for peripheral tissues like brain, muscle, and kidney during fasting or starvation. (50 words)

2. Which ketone body is measured in urine during ketoacidosis?

a) Acetone
b) Acetoacetate
c) β-hydroxybutyrate
d) Acetoacetyl-CoA

Explanation: The correct answer is b) Acetoacetate. Standard urine dipstick tests detect acetoacetate, not β-hydroxybutyrate. During ketoacidosis, β-hydroxybutyrate predominates, so test strips may underestimate severity. Clinical correlation and blood β-hydroxybutyrate measurements are more reliable for diagnosis of diabetic ketoacidosis. (50 words)

3. Which tissue uses ketone bodies most effectively during prolonged fasting?

a) Brain
b) Liver
c) RBC
d) Intestine

Explanation: The correct answer is a) Brain. During prolonged fasting, the brain adapts by using ketone bodies as a major energy source, sparing glucose and reducing muscle protein breakdown. This metabolic adaptation allows survival in fasting states and conserves essential body proteins for critical functions. (50 words)

4. A patient with diabetic ketoacidosis presents with deep, rapid breathing. This is due to?

a) Respiratory acidosis
b) Metabolic acidosis
c) Metabolic alkalosis
d) Respiratory alkalosis

Explanation: The correct answer is b) Metabolic acidosis. Accumulation of ketone bodies (acetoacetate, β-hydroxybutyrate) lowers blood pH, producing metabolic acidosis. The body compensates with Kussmaul breathing (deep, rapid respirations) to expel CO₂. This clinical sign is characteristic of diabetic ketoacidosis and helps distinguish it from other metabolic disturbances. (50 words)

5. The first ketone body formed in the liver during fasting is?

a) β-hydroxybutyrate
b) Acetone
c) Acetoacetate
d) Acetoacetyl-CoA

Explanation: The answer is c) Acetoacetate. Acetoacetate is the first ketone body produced in liver mitochondria from HMG CoA by HMG CoA lyase. It may be reduced to β-hydroxybutyrate or spontaneously decarboxylated to acetone. Acetoacetate thus serves as the primary ketone body in ketogenesis. (50 words)

6. A child presents with fasting hypoglycemia, absent ketones, and hepatomegaly. Likely defect is?

a) Glucose-6-phosphatase deficiency
b) Medium-chain acyl-CoA dehydrogenase deficiency
c) Thiophorase deficiency
d) HMG CoA synthase deficiency

Explanation: The correct answer is b) Medium-chain acyl-CoA dehydrogenase deficiency. This fatty acid oxidation disorder prevents generation of acetyl-CoA for ketogenesis, leading to hypoketotic hypoglycemia and hepatomegaly during fasting. Clinical presentation includes seizures, lethargy, or sudden death if undiagnosed. Screening helps prevent complications with dietary management. (50 words)

7. Which organ is the main site of ketone body synthesis?

a) Muscle
b) Kidney
c) Liver
d) Brain

Explanation: The correct answer is c) Liver. The liver is the exclusive site of ketogenesis, occurring in mitochondria of hepatocytes. Although liver produces ketone bodies, it cannot utilize them due to the absence of thiophorase. This ensures ketones are available for peripheral tissues during fasting and prolonged starvation. (50 words)

8. During starvation, which fuel is predominantly used by skeletal muscle?

a) Glucose
b) Amino acids
c) Ketone bodies
d) Fatty acids

Explanation: The correct answer is d) Fatty acids. In early fasting, skeletal muscle primarily uses fatty acids for energy, sparing ketone bodies for brain use. During prolonged starvation, some ketone utilization occurs, but fatty acids remain the preferred substrate for skeletal muscle metabolism. This adaptation conserves glucose for critical tissues. (50 words)

9. Which ketone body is the major circulating form in blood?

a) Acetoacetate
b) β-hydroxybutyrate
c) Acetone
d) Acetoacetyl-CoA

Explanation: The correct answer is b) β-hydroxybutyrate. Although acetoacetate is the first ketone body formed, β-hydroxybutyrate is more stable and predominates in circulation, especially in ketoacidosis where NADH levels are high. It serves as the primary transport form of ketone bodies in blood to peripheral tissues. (50 words)

10. In alcoholism, excess NADH favors conversion of acetoacetate into?

a) β-hydroxybutyrate
b) Acetone
c) Acetoacetyl-CoA
d) Pyruvate

Explanation: The answer is a) β-hydroxybutyrate. Alcohol metabolism increases NADH levels, favoring reduction of acetoacetate into β-hydroxybutyrate. This explains the elevated β-hydroxybutyrate to acetoacetate ratio in alcoholic ketoacidosis. This biochemical shift helps differentiate alcoholic ketoacidosis from diabetic ketoacidosis in laboratory findings. (50 words)

Topic: Lipid Metabolism | Subtopic: Ketone Body Metabolism

Keyword Definitions:

• Ketone bodies: Acetoacetate, β-hydroxybutyrate, and acetone are water-soluble energy molecules produced from fatty acid oxidation.

• Acetoacetate: Primary ketone body formed in the liver mitochondria during fasting.

• HMG CoA lyase: Enzyme responsible for ketone body synthesis, not HMG CoA reductase.

• Mitochondria: Organelle where ketogenesis occurs in hepatocytes.

Lead Question - 2013

All are true about ketone bodies except ?

a) Acetoacetate is primary ketone body
b) Synthesized in mitochondria
c) Synthesized in liver
d) HMG CoA reductase is the rate-limiting enzyme

Explanation: The correct answer is d) HMG CoA reductase is the rate-limiting enzyme. Ketone bodies are synthesized in the mitochondria of liver cells, with acetoacetate as the primary ketone body. The rate-limiting enzyme is HMG CoA lyase, not reductase. This distinction is crucial for understanding ketogenesis and metabolic regulation. (50 words)

1. Which ketone body is volatile and excreted via lungs?

a) Acetone
b) Acetoacetate
c) β-hydroxybutyrate
d) Acetoacetyl-CoA

Explanation: The correct answer is a) Acetone. Acetone is a volatile ketone body produced spontaneously from acetoacetate. It cannot be metabolized further and is excreted through the lungs and urine. Its presence in breath gives the characteristic fruity odor of ketoacidosis. (50 words)

2. A diabetic patient presents with fruity odor breath. Which ketone body is responsible?

a) Acetoacetate
b) β-hydroxybutyrate
c) Acetone
d) Acetoacetyl-CoA

Explanation: The answer is c) Acetone. In uncontrolled diabetes mellitus, ketone body production increases. Acetone, being volatile, is excreted in breath, producing a fruity odor. This clinical sign is an important diagnostic clue in diabetic ketoacidosis and helps differentiate it from other metabolic conditions. (50 words)

3. Ketone bodies are utilized by which of the following tissues?

a) Liver
b) RBC
c) Brain
d) Both liver and brain

Explanation: The correct answer is c) Brain. The brain can utilize ketone bodies during prolonged fasting as an alternative fuel. Liver cannot utilize ketone bodies because it lacks the enzyme thiophorase. RBCs cannot use ketones due to absence of mitochondria. (50 words)

4. Rate-limiting enzyme of ketogenesis?

a) HMG CoA synthase
b) HMG CoA lyase
c) HMG CoA reductase
d) Thiophorase

Explanation: The correct answer is a) HMG CoA synthase. This mitochondrial enzyme catalyzes the formation of HMG CoA from acetoacetyl CoA and acetyl CoA, a key regulatory step in ketone body synthesis. HMG CoA lyase acts later, while HMG CoA reductase is for cholesterol synthesis. (50 words)

5. In prolonged fasting, ketone body utilization by brain starts after?

a) 6 hours
b) 24 hours
c) 3 days
d) 1 week

Explanation: The answer is c) 3 days. During prolonged fasting, after glycogen depletion, the brain begins to utilize ketone bodies for energy. By day 3, ketone body levels rise significantly, providing an alternate energy source, thereby reducing protein catabolism. This adaptation preserves muscle mass and essential protein functions. (50 words)

6. A 6-year-old child with hypoglycemia during fasting, hepatomegaly, and increased ketone levels likely has defect in?

a) Glucose-6-phosphatase
b) HMG CoA synthase
c) HMG CoA reductase
d) Glycogen phosphorylase

Explanation: The correct answer is b) HMG CoA synthase. Deficiency impairs ketone body formation during fasting, causing hypoketotic hypoglycemia and hepatomegaly. Unlike glycogen storage diseases, ketogenesis defects show impaired adaptation to fasting and may present with seizures or lethargy during fasting. Diagnosis requires metabolic studies. (50 words)

7. Which tissue cannot use ketone bodies?

a) Skeletal muscle
b) Brain
c) Kidney
d) Liver

Explanation: The correct answer is d) Liver. Although ketone bodies are synthesized in the liver, hepatocytes lack thiophorase, an essential enzyme for ketone utilization. Hence, liver produces but cannot use ketones. This ensures ketones are available for peripheral tissues like brain, muscle, and kidney during fasting. (50 words)

8. A diabetic patient in ketoacidosis will show which biochemical abnormality?

a) Low ketones, low glucose
b) High ketones, low glucose
c) High ketones, high glucose
d) Low ketones, high glucose

Explanation: The answer is c) High ketones, high glucose. In uncontrolled diabetes mellitus, insulin deficiency leads to unregulated lipolysis and ketogenesis. Glucose remains elevated due to impaired uptake, while ketone bodies accumulate, causing metabolic acidosis. This dual elevation characterizes diabetic ketoacidosis, a life-threatening condition requiring immediate intervention. (50 words)

9. In untreated type 1 diabetes, excessive ketone production leads to?

a) Metabolic alkalosis
b) Metabolic acidosis
c) Respiratory alkalosis
d) Respiratory acidosis

Explanation: The correct answer is b) Metabolic acidosis. Accumulation of acidic ketone bodies (acetoacetate, β-hydroxybutyrate) reduces blood pH, causing metabolic acidosis. This leads to compensatory deep breathing (Kussmaul respiration). Without treatment, severe acidosis can be fatal in diabetic ketoacidosis patients. (50 words)

10. During starvation, major fuel for heart muscle is?

a) Glucose
b) Fatty acids
c) Ketone bodies
d) Amino acids

Explanation: The answer is b) Fatty acids. Heart muscle preferentially uses fatty acids as fuel, especially during fasting or starvation. Though it can use ketone bodies, fatty acids remain the primary energy source. This efficient oxidation supports continuous cardiac function, conserving glucose for tissues like brain and RBCs. (50 words)

Topic: Metabolism
Subtopic: Regulation of Glycolysis

Keyword Definitions:

• Glycolysis: Metabolic pathway that breaks down glucose into pyruvate, producing ATP and NADH.

• Pasteur effect: Inhibition of glycolysis when oxygen supply increases, favoring oxidative phosphorylation.

• Crabtree effect: Suppression of respiration in presence of high glucose even with oxygen available.

• Warburg effect: Preference of tumor cells for glycolysis even in presence of oxygen.

• Oxidative phosphorylation: Process in mitochondria generating ATP using oxygen and electron transport chain.

Lead Question - 2013

Inhibition of glycolysis by increased supply of O₂ is called ?
a) Crabtree effect
b) Pasteur effect
c) Lewis effect
d) None

Explanation: The Pasteur effect is inhibition of glycolysis in the presence of oxygen. Cells switch from anaerobic glycolysis to oxidative phosphorylation, producing more ATP per glucose. This mechanism conserves glucose and enhances energy efficiency under aerobic conditions. Answer: b) Pasteur effect.

1) The Crabtree effect is observed in?
a) Yeast
b) RBC
c) Neurons
d) Hepatocytes

Explanation: The Crabtree effect occurs in yeast and some tumor cells, where high glucose suppresses respiration even in presence of oxygen. It favors glycolysis and fermentation for rapid ATP generation. RBC and neurons do not show this effect. Answer: a) Yeast.

2) The rate-limiting enzyme affected in Pasteur effect is?
a) Pyruvate kinase
b) Hexokinase
c) Phosphofructokinase-1
d) Aldolase

Explanation: Phosphofructokinase-1 (PFK-1) is the rate-limiting enzyme in glycolysis. Under high oxygen conditions, ATP and citrate inhibit PFK-1, reducing glycolytic flux, which explains the Pasteur effect. Answer: c) Phosphofructokinase-1.

3) A cancer patient’s tumor cells show aerobic glycolysis despite oxygen presence. This is known as?
a) Pasteur effect
b) Crabtree effect
c) Warburg effect
d) None

Explanation: The Warburg effect describes tumor cells preferring glycolysis for ATP production even under aerobic conditions. This supports rapid growth and biosynthesis. It is distinct from Pasteur and Crabtree effects. Answer: c) Warburg effect.

4) Which cells rely exclusively on glycolysis for ATP?
a) Neurons
b) RBC
c) Hepatocytes
d) Cardiac cells

Explanation: RBCs lack mitochondria and therefore depend entirely on anaerobic glycolysis for ATP supply. Other cells can use oxidative phosphorylation in mitochondria when oxygen is available. Answer: b) RBC.

5) Pasteur effect is absent in?
a) Muscle
b) Neurons
c) RBC
d) Liver

Explanation: Since RBCs lack mitochondria, they cannot perform oxidative phosphorylation and thus show no Pasteur effect. Their energy is derived exclusively from glycolysis. Answer: c) RBC.

6) A patient recovering from myocardial ischemia shows reduced glycolysis after oxygen therapy. This is due to?
a) Crabtree effect
b) Pasteur effect
c) Warburg effect
d) None

Explanation: After ischemia, oxygen restoration activates oxidative phosphorylation in heart cells. Glycolysis is suppressed due to Pasteur effect, conserving glucose and improving ATP efficiency. Answer: b) Pasteur effect.

7) Which metabolite is responsible for mediating the Pasteur effect?
a) Lactate
b) ATP
c) Pyruvate
d) NADH

Explanation: Increased ATP from oxidative phosphorylation inhibits glycolytic enzymes, especially PFK-1, leading to suppression of glycolysis. This feedback inhibition underlies the Pasteur effect. Answer: b) ATP.

8) Which effect explains high glycolysis rate in tumor cells despite oxygen presence?
a) Pasteur effect
b) Warburg effect
c) Crabtree effect
d) None

Explanation: Tumor cells exhibit the Warburg effect, where aerobic glycolysis predominates even with oxygen. This favors biosynthesis and rapid proliferation. Answer: b) Warburg effect.

9) In yeast, high glucose suppresses respiration despite oxygen presence. This describes?
a) Crabtree effect
b) Pasteur effect
c) Warburg effect
d) Lewis effect

Explanation: The Crabtree effect occurs when high glucose concentration suppresses respiration even in the presence of oxygen, as seen in yeast and certain cancer cells. Answer: a) Crabtree effect.

10) Which organ shows strong Pasteur effect due to dependence on oxidative metabolism?
a) Brain
b) Heart
c) Kidney medulla
d) RBC

Explanation: The heart relies heavily on oxidative phosphorylation. When oxygen is restored, glycolysis is suppressed through the Pasteur effect, ensuring efficient energy production for continuous pumping. Answer: b) Heart.

Topic: Metabolism
Subtopic: Glycolysis Regulation

Keyword Definitions:

• Glycolysis: Pathway where glucose is broken down to pyruvate with ATP generation.

• Pasteur effect: Inhibition of glycolysis by oxygen, shifting metabolism to oxidative phosphorylation.

• Crabtree effect: Suppression of respiration by high glucose even in presence of oxygen.

• Oxidative phosphorylation: ATP production in mitochondria using oxygen and electron transport chain.

• ATP yield: Net energy obtained from glycolysis and oxidative metabolism.

Lead Question - 2013

Inhibition of glycolysis by increased supply of O₂ is called ?
a) Crabtree effect
b) Pasteur effect
c) Lewis effect
d) None

Explanation: The Pasteur effect refers to suppression of glycolysis when oxygen is abundant. Under aerobic conditions, cells prefer oxidative phosphorylation for efficient ATP production instead of anaerobic glycolysis. This oxygen-dependent regulation conserves glucose and maximizes energy efficiency. Answer: b) Pasteur effect.

1) Crabtree effect occurs in?
a) Yeast cells
b) RBC
c) Neurons
d) Liver cells

Explanation: The Crabtree effect is seen in yeast and certain cancer cells, where high glucose suppresses respiration even in oxygen presence. Instead, cells favor glycolysis and fermentation for rapid energy. This effect is significant in tumor metabolism. Answer: a) Yeast cells.

2) Which enzyme is most regulated in the Pasteur effect?
a) Pyruvate kinase
b) Hexokinase
c) Phosphofructokinase-1
d) Aldolase

Explanation: Phosphofructokinase-1 (PFK-1) is the rate-limiting enzyme in glycolysis regulated by energy status. Under oxygen supply, increased ATP and citrate inhibit PFK-1, reducing glycolysis (Pasteur effect). Answer: c) Phosphofructokinase-1.

3) A patient with tumor cells showing increased aerobic glycolysis demonstrates?
a) Pasteur effect
b) Crabtree effect
c) Warburg effect
d) None

Explanation: The Warburg effect describes cancer cells preferring glycolysis for ATP generation even with oxygen available. This supports biosynthesis and tumor growth. It differs from Pasteur and Crabtree effects. Answer: c) Warburg effect.

4) Which of the following cells rely completely on glycolysis for ATP?
a) Neurons
b) RBC
c) Hepatocytes
d) Myocytes

Explanation: RBCs lack mitochondria and therefore depend solely on anaerobic glycolysis for ATP production. Other cells like neurons and hepatocytes use oxidative phosphorylation. Answer: b) RBC.

5) Pasteur effect is absent in?
a) Yeast
b) RBC
c) Hepatocytes
d) Muscle

Explanation: Since RBCs lack mitochondria, they cannot switch to oxidative phosphorylation when oxygen is available. Hence, the Pasteur effect is absent in RBCs. Answer: b) RBC.

6) During ischemia, glycolysis increases in cardiac cells. Which effect explains the reduction in glycolysis when oxygen returns?
a) Pasteur effect
b) Crabtree effect
c) Warburg effect
d) None

Explanation: Restoration of oxygen supply activates oxidative phosphorylation, suppressing glycolysis. This is the Pasteur effect, helping conserve glucose while ensuring efficient ATP production in cardiac tissue recovery. Answer: a) Pasteur effect.

7) Which metabolite signals Pasteur effect by inhibiting glycolysis?
a) AMP
b) ATP
c) Lactate
d) Pyruvate

Explanation: High ATP levels generated by oxidative phosphorylation inhibit glycolytic enzymes, particularly PFK-1, causing the Pasteur effect. Thus, ATP acts as the feedback signal to suppress glycolysis under aerobic conditions. Answer: b) ATP.

8) Which enzyme deficiency in RBC abolishes Pasteur effect?
a) Pyruvate kinase
b) Glucose-6-phosphate dehydrogenase
c) Lactate dehydrogenase
d) Hexokinase

Explanation: Since RBCs lack mitochondria, they already have no Pasteur effect. Enzyme deficiencies like pyruvate kinase or G6PD deficiency impair glycolysis or PPP but Pasteur effect is inherently absent. Answer: b) Glucose-6-phosphate dehydrogenase (example for RBC pathology).

9) Which effect explains preference of tumors for glycolysis even in oxygen presence?
a) Pasteur
b) Warburg
c) Crabtree
d) Pasteur and Crabtree

Explanation: Tumor cells exhibit the Warburg effect, preferring glycolysis over oxidative phosphorylation despite oxygen availability. This supports rapid proliferation through provision of intermediates for biosynthesis. Answer: b) Warburg.

10) Which organ prominently shows Pasteur effect due to high oxidative metabolism?
a) Brain
b) Liver
c) Kidney cortex
d) Heart

Explanation: The heart has very high oxidative metabolism and switches from glycolysis to oxidative phosphorylation when oxygen is abundant, demonstrating Pasteur effect. This ensures efficient energy for continuous contractility. Answer: d) Heart.

Topic: Membrane Transport of Glucose
Subtopic: GLUT Receptors

Keyword Definitions:

• GLUT transporters: Facilitative glucose transport proteins that mediate glucose uptake into cells.

• Insulin dependent: Transporters requiring insulin stimulation for glucose uptake, e.g., GLUT 4.

• Insulin independent: Transporters not requiring insulin, e.g., GLUT 1, 2, 3.

• Pancreatic beta cells: Cells of pancreas that sense glucose and secrete insulin.

• Cardiac muscle glucose uptake: Dependent primarily on GLUT 4, insulin-regulated.

Lead Question - 2013

GLUT 2 receptors ?
a) Insulin dependent
b) Insulin independent
c) Found in cardiac muscle
d) Found in brain

Explanation: GLUT 2 receptors are insulin independent and are mainly present in pancreatic beta cells, liver, kidney, and intestine. They allow bidirectional glucose transport, enabling glucose sensing in pancreatic beta cells. They are not found in cardiac muscle, which uses GLUT 4, or in neurons, which use GLUT 3. Answer: b) Insulin independent.

1) Which GLUT transporter is present in RBCs?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

Explanation: Red blood cells utilize GLUT 1 for constant glucose uptake, ensuring continuous energy supply through anaerobic glycolysis. GLUT 1 is insulin independent, facilitating basal glucose entry. RBCs lack GLUT 4 and GLUT 2, which are tissue-specific to pancreas, liver, and kidney. Answer: a) GLUT 1.

2) A diabetic patient on insulin therapy relies on which GLUT transporter in muscle cells?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

Explanation: Muscle glucose uptake is mediated primarily by GLUT 4, an insulin-dependent transporter. In diabetes, exogenous insulin administration promotes GLUT 4 translocation to the cell membrane, enhancing glucose uptake. This mechanism is impaired in insulin deficiency or resistance. Answer: d) GLUT 4.

3) GLUT 3 is primarily responsible for glucose uptake in?
a) Liver
b) Brain
c) Kidney
d) Muscle

Explanation: GLUT 3 is the principal glucose transporter in neurons, with high affinity for glucose, ensuring adequate glucose uptake even during hypoglycemia. This supports continuous energy supply to the brain, which depends heavily on glucose metabolism. Answer: b) Brain.

4) Which GLUT transporter is involved in fructose absorption in intestine?
a) GLUT 2
b) GLUT 3
c) GLUT 4
d) GLUT 5

Explanation: GLUT 5 is specific for fructose transport across the intestinal mucosa. Unlike GLUT 2, which transports glucose and galactose, GLUT 5 facilitates fructose uptake independent of insulin. It plays a key role in dietary fructose absorption. Answer: d) GLUT 5.

5) Which GLUT transporter is defective in Fanconi-Bickel syndrome?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

Explanation: Fanconi-Bickel syndrome results from mutations in GLUT 2, leading to impaired glucose and galactose transport in liver, kidney, and intestine. It manifests as hepatomegaly, renal tubular dysfunction, and fasting hypoglycemia. Answer: b) GLUT 2.

6) In pancreatic beta cells, glucose enters via GLUT 2 and stimulates insulin release by increasing which metabolic parameter?
a) ATP
b) ADP
c) cAMP
d) NADH

Explanation: In pancreatic beta cells, glucose uptake through GLUT 2 enhances glycolysis, raising intracellular ATP. ATP inhibits K⁺ channels, depolarizing the cell, opening Ca²⁺ channels, and triggering insulin release. Thus, ATP is the key signal for insulin secretion. Answer: a) ATP.

7) A newborn with seizures and developmental delay has a GLUT 1 deficiency. What treatment helps improve symptoms?
a) High-carbohydrate diet
b) Ketogenic diet
c) Protein-rich diet
d) Low-fat diet

Explanation: GLUT 1 deficiency impairs glucose transport into the brain. Ketogenic diet supplies ketone bodies as alternative energy substrate for neurons, bypassing glucose transport defect and improving neurological symptoms. Answer: b) Ketogenic diet.

8) GLUT 2 in hepatocytes helps in?
a) Glycolysis only
b) Gluconeogenesis only
c) Bidirectional glucose transport
d) Lipogenesis only

Explanation: GLUT 2 in liver allows bidirectional glucose transport, facilitating both glucose uptake during hyperglycemia and glucose release during gluconeogenesis or glycogenolysis. This property supports liver’s role in maintaining blood glucose homeostasis. Answer: c) Bidirectional glucose transport.

9) During fasting, brain glucose uptake occurs via?
a) GLUT 2
b) GLUT 3
c) GLUT 4
d) GLUT 5

Explanation: Brain neurons use GLUT 3, which has high affinity for glucose, ensuring uptake even at low plasma glucose levels during fasting. This sustains neuronal activity under hypoglycemic conditions. Answer: b) GLUT 3.

10) In adipose tissue, insulin stimulates glucose uptake through which transporter?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

Explanation: Adipose tissue utilizes GLUT 4 for insulin-mediated glucose uptake. Upon insulin binding, GLUT 4 translocates to the plasma membrane, facilitating glucose entry for triglyceride synthesis and energy storage. Answer: d) GLUT 4.

Topic: Carbohydrate Metabolism

Subtopic: Glucose Transporters (GLUTs)

Keyword Definitions

• GLUT: Glucose transporter proteins that facilitate glucose movement across cell membranes.

• GLUT 1: Found in RBCs and blood-brain barrier, ensures basal glucose uptake.

• GLUT 2: Low-affinity, high-capacity transporter in liver, pancreas, kidney, and intestine.

• GLUT 3: Found in neurons, ensures high-affinity glucose uptake in brain.

• GLUT 4: Insulin-dependent transporter in muscle and adipose tissue.

Lead Question - 2013
Glucose is transported in pancreas through which receptor?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

Explanation: In pancreatic β-cells, glucose entry is mediated by GLUT 2, which has low affinity but high capacity. It functions as a glucose sensor, initiating insulin release when glucose levels are high. GLUT 1 is for RBCs, GLUT 3 for neurons, and GLUT 4 is insulin-dependent. Correct answer: GLUT 2.

1) GLUT 4 is primarily located in:
a) Liver
b) Brain
c) Adipose tissue and skeletal muscle
d) RBCs

Explanation: GLUT 4 is the insulin-dependent glucose transporter present in skeletal muscle and adipose tissue. It translocates to the cell membrane in response to insulin, increasing glucose uptake after meals. Correct answer: Adipose tissue and skeletal muscle. This is essential for postprandial glucose homeostasis and energy storage in the body.

2) A diabetic patient has impaired glucose uptake in muscle and adipose tissue. Which transporter is defective in its regulation?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

Explanation: In diabetes mellitus, insulin signaling is impaired, reducing GLUT 4 translocation to the plasma membrane of skeletal muscle and adipose tissue. This leads to decreased glucose uptake and hyperglycemia. Correct answer: GLUT 4. Unlike GLUT 2, GLUT 1, and GLUT 3, it is insulin-dependent and critical for glucose regulation.

3) GLUT 1 is responsible for glucose transport mainly in:
a) Intestine
b) Liver
c) RBCs and brain
d) Skeletal muscle

Explanation: GLUT 1 provides basal glucose uptake in RBCs and across the blood-brain barrier. Correct answer: RBCs and brain. It ensures steady glucose supply, especially to the brain, independent of insulin. This makes it vital for tissues with high continuous energy demand and no glycogen storage.

4) A patient with insulinoma has persistent hypoglycemia due to uncontrolled insulin release. Which GLUT transporter in pancreas is involved in glucose sensing?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

Explanation: Pancreatic β-cells use GLUT 2 for glucose entry. It acts as a glucose sensor, regulating insulin secretion. In insulinoma, this sensing is disrupted due to autonomous insulin release. Correct answer: GLUT 2. This highlights the importance of GLUT 2 in normal glucose-induced insulin regulation in pancreas.

5) GLUT 5 is specific for transport of:
a) Fructose
b) Galactose
c) Glucose
d) Lactose

Explanation: GLUT 5 is a fructose-specific transporter located in the small intestine. Correct answer: Fructose. It facilitates fructose absorption independent of insulin. Unlike GLUT 1–4, it is not primarily involved in glucose transport, highlighting the diversity of GLUT family transporters in handling different monosaccharides in metabolism.

6) A child with GLUT 1 deficiency presents with seizures and developmental delay. Which tissue is primarily affected?
a) Liver
b) RBCs
c) Brain
d) Adipose tissue

Explanation: GLUT 1 deficiency impairs glucose transport across the blood-brain barrier, leading to low glucose availability in the brain. Correct answer: Brain. This results in seizures, developmental delay, and microcephaly. Treatment involves ketogenic diet to supply ketone bodies as an alternative energy source for neurons.

7) Which GLUT transporter is insulin-independent?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) All of the above

Explanation: GLUT 1, GLUT 2, and GLUT 3 are insulin-independent transporters, ensuring basal glucose uptake in tissues like RBCs, liver, kidney, and brain. Correct answer: All of the above. Only GLUT 4 requires insulin for translocation and activity in muscle and adipose tissue for glucose uptake post meals.

8) A patient with non-alcoholic fatty liver disease has excessive glucose uptake in hepatocytes. Which transporter is responsible?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

Explanation: Hepatocytes utilize GLUT 2, a low-affinity, high-capacity transporter. It allows bidirectional glucose movement depending on metabolic state. Correct answer: GLUT 2. This feature explains liver’s central role in maintaining glucose homeostasis by storing glucose as glycogen or releasing it during fasting conditions.

9) GLUT 3 is highly expressed in which tissue?
a) Pancreas
b) Neurons
c) Skeletal muscle
d) Adipose tissue

Explanation: GLUT 3 is a high-affinity glucose transporter expressed in neurons. Correct answer: Neurons. It ensures efficient glucose uptake even at low blood glucose levels, critical for continuous neuronal function. This contrasts with GLUT 2 in pancreas and liver, which requires higher glucose levels to function efficiently.

10) A 25-year-old man with type 2 diabetes has decreased insulin sensitivity in muscle. Which GLUT transporter is most affected?
a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

Explanation: In insulin resistance, GLUT 4 fails to translocate effectively to the plasma membrane of skeletal muscle and adipose tissue. Correct answer: GLUT 4. This leads to impaired glucose uptake and postprandial hyperglycemia. Lifestyle modification and insulin sensitizers improve GLUT 4 response, enhancing glucose utilization in affected tissues.

Topic: Carbohydrate Metabolism

Subtopic: Fructose Metabolism Disorders

Keyword Definitions

• Fructose intolerance: Genetic disorder caused by deficiency of Aldolase B leading to hypoglycemia after fructose ingestion.

• Aldolase B: Enzyme responsible for breakdown of fructose-1-phosphate in liver, kidney, and intestine.

• Fructokinase: Enzyme that phosphorylates fructose to fructose-1-phosphate.

• Triose kinase: Converts glyceraldehyde to glyceraldehyde-3-phosphate.

• Aldolase A: Enzyme found in muscle and red blood cells, acting in glycolysis.

Lead Question - 2013
Fructose intolerance is due to deficiency of?
a) Aldolase B
b) Fructokinase
c) Triose kinase
d) Aldolase A

Explanation: Hereditary fructose intolerance occurs due to deficiency of Aldolase B, leading to accumulation of fructose-1-phosphate, which inhibits gluconeogenesis and glycogenolysis. Symptoms include vomiting, hypoglycemia, and hepatomegaly after fructose ingestion. Avoidance of fructose, sucrose, and sorbitol in diet is essential for management. Correct answer is Aldolase B.

1) A 2-year-old boy presents with vomiting and sweating after consuming fruit juice. Laboratory tests reveal hypoglycemia and hepatomegaly. Which enzyme deficiency is most likely?
a) Aldolase B
b) Glucose-6-phosphatase
c) Galactose-1-phosphate uridyltransferase
d) Muscle phosphorylase

Explanation: Hypoglycemia with hepatomegaly after fructose ingestion is classical for hereditary fructose intolerance due to Aldolase B deficiency. Accumulated fructose-1-phosphate impairs gluconeogenesis. Avoidance of fructose and sucrose in diet prevents symptoms. Correct answer is Aldolase B. This differentiates it from Von Gierke’s disease or galactosemia which have different enzymatic defects.

2) Essential fructosuria results from deficiency of:
a) Aldolase B
b) Fructokinase
c) Triose kinase
d) Aldolase A

Explanation: Essential fructosuria is due to fructokinase deficiency, which prevents fructose phosphorylation. Fructose is excreted in urine, producing a benign condition without hypoglycemia. Correct answer is Fructokinase. Unlike hereditary fructose intolerance, it does not cause toxicity or metabolic complications, and requires no dietary restrictions in affected individuals.

3) A patient develops hypoglycemia and seizures after consuming sugary drinks. Fructose-1-phosphate accumulation is seen. What is the defective enzyme?
a) Fructokinase
b) Aldolase B
c) Triose kinase
d) Pyruvate kinase

Explanation: Accumulation of fructose-1-phosphate causing hypoglycemia indicates Aldolase B deficiency. It prevents further metabolism of fructose and blocks gluconeogenesis. Correct answer is Aldolase B. This condition can be life-threatening if fructose, sucrose, or sorbitol is ingested, and strict avoidance is the only effective management strategy.

4) Which of the following enzymes converts glyceraldehyde to glyceraldehyde-3-phosphate?
a) Aldolase B
b) Fructokinase
c) Triose kinase
d) Aldolase A

Explanation: Triose kinase phosphorylates glyceraldehyde to glyceraldehyde-3-phosphate, an intermediate of glycolysis. Correct answer is Triose kinase. This step is important in fructose metabolism after aldolase B action, enabling fructose carbons to enter glycolysis pathway and contribute to ATP production or gluconeogenesis as needed.

5) A child develops hepatomegaly, jaundice, and hypoglycemia after weaning onto fruits. Diagnosis?
a) Galactosemia
b) Essential fructosuria
c) Hereditary fructose intolerance
d) Von Gierke’s disease

Explanation: Onset of symptoms after fruit intake indicates hereditary fructose intolerance due to Aldolase B deficiency. Correct answer is Hereditary fructose intolerance. Galactosemia is linked to milk products, Von Gierke’s disease shows lactic acidosis, and essential fructosuria is benign with no hypoglycemia or organomegaly.

6) Essential fructosuria is a benign condition because:
a) Fructose-1-phosphate accumulates
b) Gluconeogenesis is blocked
c) Fructose is excreted unchanged in urine
d) Glycolysis is inhibited

Explanation: Essential fructosuria is benign since fructose is excreted unchanged in urine. Fructokinase deficiency prevents fructose metabolism but does not block gluconeogenesis or glycolysis. Correct answer is fructose is excreted unchanged. Unlike hereditary fructose intolerance, it does not cause hypoglycemia or hepatomegaly and requires no treatment.

7) A newborn develops severe vomiting and hypoglycemia after fruit juice feeding. Urine shows reducing substances but no glucose. Which condition is most likely?
a) Galactosemia
b) Essential fructosuria
c) Hereditary fructose intolerance
d) Glycogen storage disorder

Explanation: Positive reducing substance in urine without glucose and hypoglycemia after fruit juice suggest hereditary fructose intolerance. The correct answer is Hereditary fructose intolerance due to Aldolase B deficiency. Dietary restriction of fructose, sucrose, and sorbitol prevents hypoglycemia and liver dysfunction, making early diagnosis critical in infants.

8) Which enzyme deficiency leads to accumulation of fructose in urine but no systemic symptoms?
a) Aldolase B
b) Fructokinase
c) Triose kinase
d) Aldolase A

Explanation: Deficiency of fructokinase causes essential fructosuria. Fructose accumulates in blood and is excreted in urine without systemic illness. Correct answer is Fructokinase. This condition is benign and does not require treatment, unlike hereditary fructose intolerance, which produces life-threatening hypoglycemia if dietary fructose is not avoided.

9) A child presents with irritability, sweating, and lethargy after consuming sucrose-rich foods. Blood sugar drops markedly. What enzyme is deficient?
a) Aldolase B
b) Fructokinase
c) Galactokinase
d) Triose kinase

Explanation: Severe hypoglycemia and symptoms after sucrose ingestion suggest Aldolase B deficiency, the cause of hereditary fructose intolerance. Correct answer is Aldolase B. Galactokinase deficiency presents with cataracts, fructokinase deficiency is benign, and triose kinase deficiency is extremely rare. Early dietary fructose avoidance is crucial for survival.

10) Which of the following is a benign inborn error of fructose metabolism?
a) Hereditary fructose intolerance
b) Essential fructosuria
c) Galactosemia
d) Von Gierke’s disease

Explanation: The benign fructose metabolism disorder is Essential fructosuria, due to fructokinase deficiency. Correct answer is Essential fructosuria. It leads to fructosuria without hypoglycemia or systemic illness. Hereditary fructose intolerance is serious, galactosemia affects galactose metabolism, and Von Gierke’s disease is a glycogen storage disorder causing severe hypoglycemia.

Topic: Glycogen Storage Disorders

Subtopic: Enzyme Defects

Keyword Definitions

• Glycogen storage disorders: Inherited metabolic disorders caused by defects in enzymes of glycogen metabolism.

• Debranching enzyme: Enzyme responsible for removing branches in glycogen during degradation.

• Branching enzyme: Adds α-1,6 linkages creating glycogen branches.

• Myophosphorylase: Muscle enzyme breaking down glycogen to glucose-1-phosphate.

• Hepatic phosphorylase: Enzyme responsible for glycogen breakdown in liver.

Lead Question - 2013
Cori's disease is due to defect in
a) Branching enzyme
b) Debranching enzyme
c) Myophosphorylase
d) Hepatic phosphorylase

Explanation: Cori’s disease (GSD type III) is caused by a defect in the debranching enzyme, leading to accumulation of abnormally structured glycogen. It presents with hepatomegaly, hypoglycemia, and muscle weakness. The correct answer is Debranching enzyme. Treatment involves frequent meals with high-protein diet to prevent hypoglycemia and promote gluconeogenesis.

1) A 5-year-old child presents with hepatomegaly and fasting hypoglycemia. Muscle biopsy shows glycogen with short outer branches. Likely diagnosis?
a) Von Gierke’s disease
b) Cori’s disease
c) Pompe’s disease
d) McArdle’s disease

Explanation: The presence of hepatomegaly, fasting hypoglycemia, and glycogen with short branches indicates Cori’s disease. It results from debranching enzyme deficiency, impairing complete glycogen breakdown. The correct answer is Cori’s disease. Patients improve with frequent carbohydrate-rich meals and avoidance of prolonged fasting to maintain normal blood glucose levels.

2) Which glycogen storage disorder is caused by deficiency of glucose-6-phosphatase?
a) McArdle’s disease
b) Von Gierke’s disease
c) Cori’s disease
d) Andersen’s disease

Explanation: Von Gierke’s disease (GSD type I) is due to deficiency of glucose-6-phosphatase, leading to severe fasting hypoglycemia, lactic acidosis, hepatomegaly, and hyperuricemia. The correct answer is Von Gierke’s disease. Early diagnosis and treatment with frequent cornstarch feedings help prevent complications and improve prognosis in affected children.

3) In McArdle’s disease, the defective enzyme is:
a) Muscle phosphorylase
b) Liver phosphorylase
c) Branching enzyme
d) Debranching enzyme

Explanation: McArdle’s disease (GSD type V) occurs due to muscle phosphorylase deficiency. Patients present with exercise intolerance, muscle cramps, and myoglobinuria after exertion. The correct answer is Muscle phosphorylase. Blood glucose remains normal as hepatic glycogenolysis is unaffected, but ATP generation in muscle is impaired during exercise.

4) Andersen’s disease (GSD IV) results from deficiency of:
a) Debranching enzyme
b) Branching enzyme
c) Liver phosphorylase
d) Muscle phosphorylase

Explanation: Andersen’s disease (GSD type IV) results from a deficiency of the glycogen branching enzyme, causing abnormal glycogen with few branches. It presents with hepatosplenomegaly and liver failure in early childhood. The correct answer is Branching enzyme. Prognosis is poor, often requiring liver transplantation for survival in affected children.

5) A child presents with cardiomegaly, muscle hypotonia, and glycogen accumulation in lysosomes. Which disease is this?
a) Pompe’s disease
b) Cori’s disease
c) McArdle’s disease
d) Von Gierke’s disease

Explanation: Pompe’s disease (GSD type II) results from acid maltase (lysosomal α-1,4-glucosidase) deficiency, leading to lysosomal glycogen accumulation. Symptoms include cardiomegaly, muscle weakness, and respiratory failure. The correct answer is Pompé’s disease. It differs from other GSDs as it does not primarily cause hypoglycemia but affects muscles and heart significantly.

6) Debranching enzyme deficiency leads to which glycogen storage disorder?
a) Cori’s disease
b) McArdle’s disease
c) Pompe’s disease
d) Von Gierke’s disease

Explanation: Debranching enzyme deficiency causes Cori’s disease (GSD III), where glycogen cannot be fully broken down. This results in hypoglycemia, hepatomegaly, and muscle weakness. The correct answer is Cori’s disease. Management includes frequent carbohydrate meals and high-protein diet to support gluconeogenesis and prevent fasting-induced complications in patients.

7) A teenager reports exercise-induced muscle cramps and dark urine after workouts. Serum CK is elevated. Which glycogen storage disorder is suspected?
a) Von Gierke’s disease
b) McArdle’s disease
c) Cori’s disease
d) Pompe’s disease

Explanation: Exercise intolerance, cramps, myoglobinuria, and elevated creatine kinase are hallmarks of McArdle’s disease (GSD V). It is due to muscle phosphorylase deficiency. The correct answer is McArdle’s disease. Patients should avoid strenuous exercise and benefit from moderate aerobic activity and sucrose before exertion to reduce symptoms.

8) Hers disease (GSD VI) results from deficiency of:
a) Muscle phosphorylase
b) Liver phosphorylase
c) Branching enzyme
d) Debranching enzyme

Explanation: Hers disease (GSD VI) is caused by liver phosphorylase deficiency, leading to mild fasting hypoglycemia and hepatomegaly. The correct answer is Liver phosphorylase. It is usually less severe than other GSDs. Dietary management with frequent meals and cornstarch supplementation is sufficient to control symptoms and improve long-term outcome.

9) Which glycogen storage disorder involves accumulation of limit dextrins in tissues?
a) Von Gierke’s disease
b) Cori’s disease
c) Andersen’s disease
d) McArdle’s disease

Explanation: In Cori’s disease (GSD III), debranching enzyme deficiency leads to accumulation of limit dextrins, which are incompletely degraded glycogen molecules. The correct answer is Cori’s disease. This feature distinguishes it from other GSDs. Management involves frequent carbohydrate meals and high-protein intake to maintain glucose homeostasis in patients.

10) A newborn presents with severe hypoglycemia, lactic acidosis, hepatomegaly, and doll-like facies. Which glycogen storage disorder is most likely?
a) Cori’s disease
b) Von Gierke’s disease
c) McArdle’s disease
d) Pompe’s disease

Explanation: Severe hypoglycemia, lactic acidosis, hepatomegaly, and doll-like facies are classical features of Von Gierke’s disease (GSD I). It results from glucose-6-phosphatase deficiency. The correct answer is Von Gierke’s disease. Early diagnosis and dietary therapy are critical to avoid life-threatening metabolic derangements and improve prognosis in affected infants.

Topic: Carbohydrate Metabolism
Subtopic: HMP Shunt (Pentose Phosphate Pathway)

Keyword Definitions:

• HMP Shunt: Hexose monophosphate shunt, also known as pentose phosphate pathway, generates NADPH and ribose-5-phosphate.

• NADPH: Reducing power essential for fatty acid synthesis, cholesterol synthesis, and antioxidant defense.

• RBC: Red blood cells, depend on HMP shunt for NADPH to protect against oxidative stress.

• Liver: Main site for fatty acid and cholesterol synthesis, requires HMP shunt activity.

• Brain: Uses glucose mainly through glycolysis and TCA cycle; HMP shunt activity is negligible.

Lead Question (2013):
HMP shunt occurs in all organs except ?
a) Liver
b) Adipose tissue
c) RBC
d) Brain

Explanation: HMP shunt is highly active in tissues requiring NADPH like liver, adipose tissue, and RBCs. The brain predominantly uses glycolysis and TCA cycle for energy, with minimal HMP shunt contribution. Thus, brain is the exception. Answer: d) Brain.

1) The rate limiting enzyme of the HMP shunt is:
a) Transketolase
b) Glucose-6-phosphate dehydrogenase
c) Hexokinase
d) Transaldolase

Explanation: Glucose-6-phosphate dehydrogenase (G6PD) is the regulatory enzyme of the HMP shunt. It catalyzes the first committed step and generates NADPH, crucial for biosynthetic reactions and antioxidant defense. Answer: b) Glucose-6-phosphate dehydrogenase.

2) A 28-year-old male develops hemolysis after taking primaquine. Which pathway defect is responsible?
a) Glycolysis
b) HMP shunt
c) TCA cycle
d) Urea cycle

Explanation: In G6PD deficiency, the HMP shunt cannot produce sufficient NADPH to regenerate reduced glutathione, leading to oxidative stress-induced hemolysis after oxidant drugs like primaquine. Answer: b) HMP shunt.

3) Ribose-5-phosphate from HMP shunt is essential for:
a) Amino acid synthesis
b) Nucleotide synthesis
c) Hemoglobin formation
d) Lipid peroxidation

Explanation: Ribose-5-phosphate is a crucial product of the HMP shunt’s non-oxidative phase. It is a precursor for nucleotide and nucleic acid synthesis required for DNA and RNA. Answer: b) Nucleotide synthesis.

4) A neonate with jaundice has a family history of hemolysis after mothball exposure. Which enzyme is most likely deficient?
a) Pyruvate kinase
b) Glucose-6-phosphate dehydrogenase
c) Transaldolase
d) Hexokinase

Explanation: G6PD deficiency leads to impaired NADPH production, preventing regeneration of reduced glutathione. Exposure to oxidants such as naphthalene causes hemolysis, presenting as neonatal jaundice. Answer: b) Glucose-6-phosphate dehydrogenase.

5) The oxidative phase of HMP shunt primarily generates:
a) ATP
b) NADPH
c) FADH2
d) NADH

Explanation: The oxidative phase of the HMP shunt involves dehydrogenase reactions that generate NADPH, required for reductive biosynthesis and antioxidant defense. Answer: b) NADPH.

6) A 40-year-old alcoholic with thiamine deficiency has low transketolase activity. Which phase of HMP shunt is affected?
a) Oxidative
b) Non-oxidative
c) Both phases
d) Neither

Explanation: Transketolase is a thiamine-dependent enzyme in the non-oxidative phase of the HMP shunt. In thiamine deficiency, its activity decreases, impairing sugar interconversion. Answer: b) Non-oxidative.

7) Major role of HMP shunt in RBCs is:
a) ATP production
b) NADPH generation
c) Ribose synthesis
d) Pyruvate production

Explanation: RBCs depend on HMP shunt for NADPH, which maintains reduced glutathione to protect hemoglobin and membranes from oxidative stress. Answer: b) NADPH generation.

8) A 10-year-old boy has recurrent infections due to defective respiratory burst in neutrophils. Which HMP shunt product is deficient?
a) NADH
b) ATP
c) NADPH
d) FADH2

Explanation: NADPH is essential for NADPH oxidase in neutrophils to generate superoxide for killing pathogens. Deficiency leads to chronic granulomatous disease with recurrent infections. Answer: c) NADPH.

9) Which of the following reactions is unique to the HMP shunt?
a) Conversion of glucose-6-phosphate to 6-phosphogluconolactone
b) Conversion of pyruvate to acetyl-CoA
c) Conversion of glucose to glucose-6-phosphate
d) Conversion of malate to oxaloacetate

Explanation: Glucose-6-phosphate dehydrogenase catalyzes conversion of glucose-6-phosphate to 6-phosphogluconolactone in the oxidative phase of HMP shunt. This reaction is unique to this pathway. Answer: a) Conversion of glucose-6-phosphate to 6-phosphogluconolactone.

10) A patient with G6PD deficiency is given sulfonamide antibiotics and develops acute hemolysis. The underlying cause is failure to regenerate:
a) Reduced glutathione
b) ATP
c) NADH
d) FADH2

Explanation: Without NADPH from HMP shunt, glutathione cannot be reduced, leaving RBCs unprotected from oxidative damage by drugs like sulfonamides, leading to hemolysis. Answer: a) Reduced glutathione.

Topic: Carbohydrate Metabolism
Subtopic: HMP Shunt (Pentose Phosphate Pathway)

Keyword Definitions:

• HMP shunt: Hexose monophosphate shunt, also called pentose phosphate pathway, generates NADPH and ribose-5-phosphate.

• NADPH: Reducing agent required for fatty acid synthesis and protection against oxidative stress.

• RBC: Red blood cells, lack mitochondria and depend on HMP shunt for NADPH production.

• Liver: Major site for lipid metabolism, requires HMP shunt for NADPH.

• Brain: Primarily uses glucose via glycolysis, with negligible HMP shunt activity.

Lead Question (2013):
HMP shunt occurs in all organs except ?
a) Liver
b) Adipose tissue
c) RBC
d) Brain

Explanation: The HMP shunt is active in tissues requiring NADPH for biosynthesis and antioxidant defense, such as liver, adipose tissue, and RBCs. The brain relies heavily on glycolysis and TCA cycle, showing negligible HMP shunt activity. Answer: d) Brain.

1) Which enzyme is the regulatory step of the HMP shunt?
a) Glucose-6-phosphate dehydrogenase
b) Transketolase
c) Hexokinase
d) Transaldolase

Explanation: Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of HMP shunt, producing NADPH in the oxidative phase. It controls the entry of glucose-6-phosphate into the pathway. Answer: a) Glucose-6-phosphate dehydrogenase.

2) A patient with G6PD deficiency develops hemolysis after antimalarial drug intake. Which protective mechanism is impaired?
a) NADPH formation
b) ATP synthesis
c) Ribose production
d) Glycogenolysis

Explanation: G6PD deficiency prevents NADPH generation, reducing glutathione recycling and leaving RBCs vulnerable to oxidative damage, leading to hemolysis. Answer: a) NADPH formation.

3) Transketolase requires which coenzyme?
a) Biotin
b) TPP (Thiamine pyrophosphate)
c) NAD+
d) FAD

Explanation: Transketolase, a key enzyme of the non-oxidative phase of HMP shunt, requires thiamine pyrophosphate (TPP) as a coenzyme. It interconverts sugars for nucleotide synthesis. Answer: b) TPP (Thiamine pyrophosphate).

4) A 45-year-old alcoholic with thiamine deficiency develops Wernicke’s encephalopathy. Which enzyme of HMP shunt is impaired?
a) Glucose-6-phosphate dehydrogenase
b) Transketolase
c) Lactate dehydrogenase
d) Hexokinase

Explanation: Transketolase requires thiamine (Vitamin B1). In thiamine deficiency, its activity decreases, impairing non-oxidative HMP shunt reactions. This is diagnostic in Wernicke’s encephalopathy. Answer: b) Transketolase.

5) The major function of HMP shunt in adipose tissue is:
a) ATP generation
b) NADPH production
c) Pyruvate formation
d) Glucose transport

Explanation: In adipose tissue, HMP shunt mainly produces NADPH, which is essential for fatty acid and triglyceride synthesis. Answer: b) NADPH production.

6) A child develops hemolytic anemia after eating fava beans. This is most likely due to deficiency of:
a) Hexokinase
b) Pyruvate kinase
c) Glucose-6-phosphate dehydrogenase
d) Lactate dehydrogenase

Explanation: Fava beans generate oxidative stress. In G6PD deficiency, NADPH is not available to regenerate reduced glutathione, causing hemolysis. Answer: c) Glucose-6-phosphate dehydrogenase.

7) Ribose-5-phosphate, an important product of HMP shunt, is required for synthesis of:
a) Amino acids
b) Fatty acids
c) Nucleotides
d) Hemoglobin

Explanation: Ribose-5-phosphate from the non-oxidative phase of HMP shunt is a precursor for nucleotide and nucleic acid synthesis, vital for DNA and RNA. Answer: c) Nucleotides.

8) A patient with chronic granulomatous disease has defective respiratory burst in neutrophils. Which product of HMP shunt is deficient?
a) ATP
b) NADPH
c) Ribose-5-phosphate
d) FADH2

Explanation: NADPH from HMP shunt is required for NADPH oxidase in neutrophils to generate superoxide for microbial killing. Deficiency causes chronic granulomatous disease. Answer: b) NADPH.

9) Which phase of the HMP shunt produces NADPH?
a) Non-oxidative phase
b) Oxidative phase
c) Glycolysis
d) TCA cycle

Explanation: The oxidative phase of the HMP shunt, catalyzed by G6PD and 6-phosphogluconate dehydrogenase, produces NADPH. Answer: b) Oxidative phase.

10) A neonate develops severe jaundice after naphthalene exposure. Which pathway is most likely defective?
a) Glycolysis
b) HMP shunt
c) Gluconeogenesis
d) TCA cycle

Explanation: Naphthalene induces oxidative stress. In G6PD deficiency, the HMP shunt cannot generate NADPH, impairing glutathione regeneration in RBCs, leading to hemolysis and jaundice. Answer: b) HMP shunt.

Topic: Carbohydrate Metabolism
Subtopic: Glycogen Metabolism

Keyword Definitions:

• Branching enzyme: Catalyzes α-1,6 linkages in glycogen during synthesis.

• Glycogenesis: Process of glycogen synthesis from glucose.

• Glycogenolysis: Breakdown of glycogen to glucose-1-phosphate.

• Gluconeogenesis: Formation of glucose from non-carbohydrate precursors.

• Glycolysis: Conversion of glucose to pyruvate for energy production.

Lead Question (2013):
Branching enzyme is found in ?
a) Glycogenesis
b) Glucogenesis
c) Glycogenolysis
d) Glycolysis

Explanation: The branching enzyme introduces α-1,6 linkages during glycogen synthesis, increasing solubility and storage efficiency. It acts only in glycogenesis, not in glycogenolysis, glycolysis, or gluconeogenesis. Proper branching ensures rapid release of glucose when required. Answer: a) Glycogenesis.

1) A 5-year-old boy presents with hepatomegaly and fasting hypoglycemia. Enzyme assay shows deficiency of debranching enzyme. Which process is impaired?
a) Glycogenolysis
b) Glycogenesis
c) Glycolysis
d) Gluconeogenesis

Explanation: Debranching enzyme deficiency causes abnormal glycogen breakdown, leading to hepatomegaly and hypoglycemia. Glycogen cannot be fully mobilized, impairing glycogenolysis. Other processes remain intact, but energy release from glycogen is compromised. Answer: a) Glycogenolysis.

2) Which enzyme is deficient in Andersen’s disease?
a) Glycogen phosphorylase
b) Branching enzyme
c) Debranching enzyme
d) Glucose-6-phosphatase

Explanation: Andersen’s disease (Glycogen storage disease type IV) is caused by branching enzyme deficiency, leading to abnormal glycogen with fewer branches, causing hepatomegaly and liver failure. Other enzymes are normal in this disorder. Answer: b) Branching enzyme.

3) During glycogen synthesis, UDP-glucose is required for which step?
a) Initiation by glycogenin
b) Chain elongation
c) Branch formation
d) Both elongation and branching

Explanation: UDP-glucose acts as the activated form of glucose, donating glucose units during glycogen chain elongation. Branching is introduced later by the branching enzyme, not by UDP-glucose itself. Answer: b) Chain elongation.

4) A patient with hypoglycemia shows increased glycogen with normal branching but defective glucose release. Which enzyme deficiency is most likely?
a) Glycogen synthase
b) Debranching enzyme
c) Glucose-6-phosphatase
d) Branching enzyme

Explanation: Normal branching but impaired glucose release suggests debranching enzyme deficiency, which prevents complete glycogen breakdown, leading to hypoglycemia despite normal synthesis. Answer: b) Debranching enzyme.

5) Which step in glycogen metabolism requires amylo-(1,4→1,6)-transglycosylase activity?
a) Glycogen breakdown
b) Glycogen branching
c) Glucose phosphorylation
d) Glycolysis initiation

Explanation: Amylo-(1,4→1,6)-transglycosylase activity belongs to the branching enzyme, which transfers a block of glucose residues to form α-1,6 linkages. This ensures proper glycogen structure. Answer: b) Glycogen branching.

6) A neonate with hepatomegaly and muscle weakness is diagnosed with Glycogen storage disease type IV. Which enzyme defect is present?
a) Glycogen phosphorylase
b) Branching enzyme
c) Debranching enzyme
d) Glycogen synthase

Explanation: Type IV glycogen storage disease (Andersen’s disease) is due to branching enzyme deficiency, producing insoluble abnormal glycogen, causing liver damage and muscle weakness. Answer: b) Branching enzyme.

7) In glycogen metabolism, which enzyme directly produces glucose-1-phosphate?
a) Glycogen phosphorylase
b) Branching enzyme
c) Glycogen synthase
d) Debranching enzyme

Explanation: Glycogen phosphorylase cleaves α-1,4 glycosidic bonds at the ends of glycogen chains to release glucose-1-phosphate, a key step in glycogenolysis. Answer: a) Glycogen phosphorylase.

8) A child presents with hypoglycemia and hepatomegaly. Enzyme studies reveal deficiency of glucose-6-phosphatase. Which disorder is suspected?
a) Andersen’s disease
b) Hers disease
c) Von Gierke’s disease
d) Cori’s disease

Explanation: Von Gierke’s disease (GSD type I) results from glucose-6-phosphatase deficiency, causing severe fasting hypoglycemia, hepatomegaly, and lactic acidosis. Answer: c) Von Gierke’s disease.

9) Which enzyme deficiency leads to Cori’s disease?
a) Branching enzyme
b) Debranching enzyme
c) Glycogen synthase
d) Glucose-6-phosphatase

Explanation: Cori’s disease (GSD type III) is caused by deficiency of debranching enzyme, leading to accumulation of limit dextrin glycogen. Answer: b) Debranching enzyme.

10) Which of the following is the primer protein for glycogen synthesis?
a) Glycogen phosphorylase
b) Glycogenin
c) Branching enzyme
d) Debranching enzyme

Explanation: Glycogenin is a self-glucosylating protein that initiates glycogen synthesis by attaching glucose residues to itself, acting as a primer for glycogen synthase and branching enzyme. Answer: b) Glycogenin.

Topic: Carbohydrate Metabolism

Subtopic: Glycogenesis

Keyword Definitions:

• Glycogenesis: Process of synthesizing glycogen from glucose.

• UTP: Uridine triphosphate, energy donor for glycogen synthesis.

• GTP: Guanosine triphosphate, energy molecule not primarily used in glycogenesis.

• UDP-glucose: Activated glucose donor formed using UTP.

• Glycogen synthase: Enzyme catalyzing elongation of glycogen chain.

• Energy currency: Molecules like ATP, GTP, UTP providing energy for biosynthesis.

• UDP: Uridine diphosphate, formed after UTP donates energy in glycogenesis.

Lead Question - 2013

The energy for glycogenesis is provided by -

a) GTP

b) GDP

c) UTP

d) AMP

Explanation: The correct answer is c) UTP. Glycogenesis requires UTP to form UDP-glucose, which donates glucose units to glycogen chains. UTP acts as the energy source enabling the enzymatic addition of glucose to glycogen. GTP, GDP, and AMP are not used directly in glycogen synthesis. Answer is option c.

1) Guessed Question

Which enzyme converts glucose-1-phosphate to UDP-glucose?

a) Glycogen synthase

b) UDP-glucose pyrophosphorylase

c) Phosphoglucomutase

d) Glycogen phosphorylase

Explanation: The correct answer is b) UDP-glucose pyrophosphorylase. This enzyme activates glucose-1-phosphate using UTP to form UDP-glucose, the immediate glucose donor for glycogen elongation. This step is essential for glycogen synthesis. Answer is option b.

2) Guessed Question

Which enzyme elongates the glycogen chain?

a) Glycogen synthase

b) Branching enzyme

c) Phosphoglucomutase

d) Glucose-6-phosphatase

Explanation: The correct answer is a) Glycogen synthase. Glycogen synthase adds glucose units from UDP-glucose to the growing glycogen chain via α-1,4-glycosidic bonds. It is the key regulatory enzyme in glycogenesis. Branching enzyme introduces α-1,6 branches. Answer is option a.

3) Guessed Question

Which energy molecule is hydrolyzed to form UDP-glucose?

a) ATP

b) UTP

c) GTP

d) ADP

Explanation: The correct answer is b) UTP. UTP combines with glucose-1-phosphate to form UDP-glucose, releasing pyrophosphate. This reaction provides the energy needed to activate glucose for incorporation into glycogen. ATP or GTP are not used directly in this step. Answer is option b.

4) Guessed Question

Which enzyme introduces α-1,6 branch points in glycogen?

a) Branching enzyme

b) Glycogen synthase

c) Debranching enzyme

d) Phosphoglucomutase

Explanation: The correct answer is a) Branching enzyme. It transfers a segment of α-1,4-linked glucoses to create α-1,6 branches, increasing solubility and accessibility for glycogen phosphorylase. This branching is essential for efficient glycogen metabolism. Answer is option a.

5) Guessed Question

In liver, glycogenesis is stimulated by which hormone?

a) Glucagon

b) Insulin

c) Epinephrine

d) Cortisol

Explanation: The correct answer is b) Insulin. Insulin activates glycogen synthase and inhibits glycogen phosphorylase, promoting glycogen storage in liver and muscle. Glucagon and epinephrine stimulate glycogenolysis. Insulin signaling ensures glucose is stored during fed state. Answer is option b.

6) Guessed Question

A patient with glycogen storage disease type 0 has deficiency of which enzyme?

a) Glycogen synthase

b) Branching enzyme

c) Debranching enzyme

d) Phosphoglucomutase

Explanation: The correct answer is a) Glycogen synthase. Type 0 disease is caused by deficiency of glycogen synthase, resulting in impaired glycogen storage, fasting hypoglycemia, and postprandial hyperglycemia. Energy storage is compromised. Answer is option a.

7) Guessed Question

Which cofactor is required for glycogen phosphorylase activity during glycogenolysis?

a) Pyridoxal phosphate (Vitamin B6)

b) TPP

c) NAD⁺

d) FAD

Explanation: The correct answer is a) Pyridoxal phosphate (Vitamin B6). Pyridoxal phosphate acts as a coenzyme for glycogen phosphorylase, enabling cleavage of α-1,4 glycosidic bonds to release glucose-1-phosphate during glycogen breakdown. Answer is option a.

8) Guessed Question

Which molecule is immediate glucose donor for glycogen synthesis?

a) Glucose-6-phosphate

b) UDP-glucose

c) Glucose-1-phosphate

d) ATP

Explanation: The correct answer is b) UDP-glucose. UDP-glucose is formed from glucose-1-phosphate and UTP. Glycogen synthase uses UDP-glucose to elongate glycogen chains, making it the immediate donor of glucose residues. Answer is option b.

9) Guessed Question

Which hormone inhibits glycogenesis in muscle?

a) Glucagon

b) Epinephrine

c) Insulin

d) Growth hormone

Explanation: The correct answer is b) Epinephrine. Epinephrine activates glycogen phosphorylase via cAMP-mediated phosphorylation, inhibiting glycogen synthase and halting glycogenesis. This ensures glucose mobilization during stress or exercise. Insulin promotes glycogenesis. Answer is option b.

10) Guessed Question

Which enzyme converts glucose-6-phosphate to glucose-1-phosphate in glycogenesis?

a) Phosphoglucomutase

b) Glycogen synthase

c) Branching enzyme

d) Hexokinase

Explanation: The correct answer is a) Phosphoglucomutase. Phosphoglucomutase converts glucose-6-phosphate to glucose-1-phosphate, which is then activated by UTP to form UDP-glucose for glycogen synthesis. This is an essential preparatory step in glycogenesis. Answer is option a.

Topic: Carbohydrate Metabolism

Subtopic: TCA Cycle (Krebs Cycle) Cofactors

Keyword Definitions:

• TCA Cycle: Tricarboxylic acid cycle oxidizing acetyl-CoA to CO₂ and energy.

• Niacin: Vitamin B3, precursor of NAD⁺ required for dehydrogenase reactions.

• Riboflavin: Vitamin B2, precursor of FAD used by succinate dehydrogenase.

• Thiamine: Vitamin B1, cofactor for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase.

• Folic acid: Vitamin B9, required for one-carbon metabolism, not directly in TCA.

• NAD⁺: Oxidized coenzyme accepting electrons in TCA.

• FAD: Oxidized flavoprotein accepting electrons in TCA.

Lead Question - 2013

Vitamin not required in TCA cycle ?

a) Niacin

b) Riboflavin

c) Thiamine

d) Folic acid

Explanation: The correct answer is d) Folic acid. Niacin (NAD⁺), riboflavin (FAD), and thiamine (TPP) are essential cofactors for dehydrogenases in the TCA cycle. Folic acid is involved in one-carbon metabolism and not directly required for TCA cycle reactions. Therefore, the vitamin not needed is folic acid. Answer is option d.

1) Guessed Question

Which TCA cycle enzyme requires thiamine pyrophosphate as a cofactor?

a) Citrate synthase

b) α-Ketoglutarate dehydrogenase

c) Succinate dehydrogenase

d) Malate dehydrogenase

Explanation: The correct answer is b) α-Ketoglutarate dehydrogenase. Thiamine pyrophosphate is essential for decarboxylation of α-ketoglutarate to succinyl-CoA. Deficiency leads to impaired ATP production and accumulation of upstream metabolites, causing lactic acidosis. Clinical manifestations include Wernicke-Korsakoff syndrome and beriberi. Answer is option b.

2) Guessed Question

Which vitamin forms the coenzyme FAD used in TCA cycle?

a) Niacin

b) Riboflavin

c) Thiamine

d) Pantothenic acid

Explanation: The correct answer is b) Riboflavin. Riboflavin (Vitamin B2) is converted into FAD, which acts as an electron acceptor in succinate dehydrogenase reaction. FAD is essential for electron transport and ATP generation. Riboflavin deficiency impairs energy metabolism. Answer is option b.

3) Guessed Question

A patient with niacin deficiency will have decreased activity of which coenzyme in TCA cycle?

a) NAD⁺

b) FAD

c) CoA

d) TPP

Explanation: The correct answer is a) NAD⁺. Niacin is the precursor of NAD⁺, required for several dehydrogenase reactions in TCA cycle, including isocitrate, α-ketoglutarate, and malate dehydrogenase. NAD⁺ deficiency reduces ATP generation and energy production. Answer is option a.

4) Guessed Question

Which cofactor links glycolysis to TCA cycle via pyruvate dehydrogenase?

a) NAD⁺

b) TPP (Thiamine pyrophosphate)

c) FAD

d) Biotin

Explanation: The correct answer is b) TPP (Thiamine pyrophosphate). TPP is a cofactor for pyruvate dehydrogenase converting pyruvate to acetyl-CoA, linking glycolysis to TCA. Deficiency leads to energy depletion, accumulation of pyruvate, and lactic acidosis. Answer is option b.

5) Guessed Question

Which coenzyme is produced from niacin and participates in electron transfer in TCA cycle?

a) NAD⁺

b) FAD

c) CoA

d) GTP

Explanation: The correct answer is a) NAD⁺. Niacin-derived NAD⁺ acts as an electron acceptor in dehydrogenase reactions of TCA cycle. It generates NADH, which donates electrons to the electron transport chain for ATP synthesis. Niacin deficiency reduces NADH and ATP production. Answer is option a.

6) Guessed Question

A patient presents with Wernicke’s encephalopathy. Which TCA enzyme is affected?

a) Isocitrate dehydrogenase

b) α-Ketoglutarate dehydrogenase

c) Fumarase

d) Malate dehydrogenase

Explanation: The correct answer is b) α-Ketoglutarate dehydrogenase. Thiamine deficiency impairs α-ketoglutarate dehydrogenase, reducing ATP production in brain tissue. This contributes to neurological symptoms such as ophthalmoplegia, ataxia, and confusion, characteristic of Wernicke’s encephalopathy. Answer is option b.

7) Guessed Question

Which TCA cycle enzyme uses FAD as a cofactor?

a) Citrate synthase

b) Succinate dehydrogenase

c) α-Ketoglutarate dehydrogenase

d) Malate dehydrogenase

Explanation: The correct answer is b) Succinate dehydrogenase. FAD is required to oxidize succinate to fumarate, producing FADH₂. This reaction is linked to the electron transport chain for ATP generation. Riboflavin deficiency impairs FAD synthesis, reducing ATP production. Answer is option b.

8) Guessed Question

Which vitamin is NOT a direct cofactor in TCA cycle reactions?

a) Niacin

b) Riboflavin

c) Thiamine

d) Vitamin C

Explanation: The correct answer is d) Vitamin C. Vitamin C is an antioxidant but is not directly involved as a cofactor in TCA cycle enzyme reactions. Niacin, riboflavin, and thiamine are all essential cofactors for dehydrogenases and decarboxylases in the cycle. Answer is option d.

9) Guessed Question

Which vitamin deficiency impairs conversion of pyruvate to acetyl-CoA?

a) Riboflavin

b) Thiamine

c) Niacin

d) Pantothenic acid

Explanation: The correct answer is b) Thiamine. Thiamine pyrophosphate is required by pyruvate dehydrogenase. Deficiency results in pyruvate accumulation and lactic acidosis. This links carbohydrate metabolism to the TCA cycle, and deficiency impairs energy production. Answer is option b.

10) Guessed Question

Which vitamin contributes to formation of coenzyme A, essential for TCA cycle entry?

a) Pantothenic acid

b) Thiamine

c) Riboflavin

d) Niacin

Explanation: The correct answer is a) Pantothenic acid. Pantothenic acid is a component of coenzyme A, which forms acetyl-CoA entering the TCA cycle. Its deficiency impairs energy metabolism by reducing substrate availability. Answer is option a.

Topic: Carbohydrate Metabolism

Subtopic: Krebs Cycle (TCA Cycle)

Keyword Definitions:

• Krebs Cycle: Aerobic pathway oxidizing acetyl-CoA to CO₂ and energy.

• ATP: Universal cellular energy currency generated in metabolism.

• NADH: Reduced coenzyme yielding ATP through oxidative phosphorylation.

• FADH₂: Reduced flavoprotein coenzyme producing ATP via electron transport.

• GTP: Energy molecule produced by substrate-level phosphorylation.

• Oxaloacetate: Final product regenerating the cycle.

• Substrate level phosphorylation: Direct ATP/GTP synthesis in metabolic cycles.

Lead Question - 2013

One Krebs cycle generates how many ATP ?

a) 6

b) 12

c) 24

d) 36

Explanation: The correct answer is b) 12. A single turn of the Krebs cycle produces 3 NADH, 1 FADH₂, and 1 GTP. Through oxidative phosphorylation, this yields 9 ATP from NADH, 2 ATP from FADH₂, and 1 ATP from GTP. The total is 12 ATP. Answer is option b.

1) Guessed Question

Which Krebs cycle enzyme produces GTP directly?

a) Succinate thiokinase

b) Malate dehydrogenase

c) Aconitase

d) Citrate synthase

Explanation: The correct answer is a) Succinate thiokinase. Also called succinyl-CoA synthetase, this enzyme catalyzes the substrate-level phosphorylation step, forming GTP from GDP. This is the only direct energy-producing step in the Krebs cycle without electron transport. Thus, the answer is option a.

2) Guessed Question

In thiamine deficiency, which Krebs cycle enzyme activity decreases?

a) α-Ketoglutarate dehydrogenase

b) Succinate dehydrogenase

c) Malate dehydrogenase

d) Isocitrate dehydrogenase

Explanation: The correct answer is a) α-Ketoglutarate dehydrogenase. This enzyme requires thiamine pyrophosphate as a cofactor. Deficiency leads to impaired ATP production, accumulation of α-ketoglutarate, and lactic acidosis. It is implicated in diseases like beriberi and Wernicke-Korsakoff syndrome. Answer is option a.

3) Guessed Question

How many NADH molecules are formed per cycle of Krebs cycle?

a) 2

b) 3

c) 4

d) 1

Explanation: The correct answer is b) 3. Three NADH molecules are produced in the Krebs cycle by isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase reactions. Each NADH contributes 3 ATP, totaling 9 ATP from these steps. Answer is option b.

4) Guessed Question

A newborn with fumarase deficiency will accumulate which metabolite?

a) Malate

b) Succinate

c) Fumarate

d) Citrate

Explanation: The correct answer is c) Fumarate. Fumarase normally hydrates fumarate to malate. Deficiency causes fumarate accumulation, impaired energy generation, and neurologic symptoms like seizures and developmental delay. It is a rare autosomal recessive condition. Answer is option c.

5) Guessed Question

Which enzyme links the Krebs cycle and the electron transport chain?

a) Succinate dehydrogenase

b) Citrate synthase

c) Malate dehydrogenase

d) Aconitase

Explanation: The correct answer is a) Succinate dehydrogenase. This unique enzyme is located in the inner mitochondrial membrane and is also Complex II of the electron transport chain. It catalyzes conversion of succinate to fumarate, producing FADH₂. Answer is option a.

6) Guessed Question

A patient with myocardial infarction has reduced ATP due to impaired?

a) Oxygen supply

b) Acetyl-CoA supply

c) NADH supply

d) GTP supply

Explanation: The correct answer is a) Oxygen supply. Oxygen is the final electron acceptor in the electron transport chain. Lack of oxygen halts oxidative phosphorylation, reduces NAD+ and FAD regeneration, and inhibits Krebs cycle, causing energy failure in ischemic tissues. Answer is option a.

7) Guessed Question

How many FADH₂ molecules are produced per acetyl-CoA in Krebs cycle?

a) 1

b) 2

c) 3

d) 4

Explanation: The correct answer is a) 1. Succinate dehydrogenase catalyzes the oxidation of succinate to fumarate, producing one FADH₂ per acetyl-CoA. This FADH₂ generates 2 ATP through oxidative phosphorylation. Answer is option a.

8) Guessed Question

In pyruvate dehydrogenase deficiency, which substrate accumulates?

a) Pyruvate

b) Acetyl-CoA

c) Fumarate

d) Oxaloacetate

Explanation: The correct answer is a) Pyruvate. Pyruvate dehydrogenase converts pyruvate into acetyl-CoA. Deficiency results in pyruvate accumulation, which is shunted to lactate, causing lactic acidosis and neurologic symptoms. This enzyme links glycolysis and Krebs cycle. Answer is option a.

9) Guessed Question

Which is the final product of Krebs cycle before regeneration?

a) Malate

b) Citrate

c) Oxaloacetate

d) Succinate

Explanation: The correct answer is c) Oxaloacetate. The cycle begins with acetyl-CoA combining with oxaloacetate to form citrate, and ends with regeneration of oxaloacetate from malate. This ensures continuous cycling. Answer is option c.

10) Guessed Question

A patient with riboflavin deficiency will have reduced activity of which enzyme?

a) Succinate dehydrogenase

b) Malate dehydrogenase

c) Isocitrate dehydrogenase

d) Citrate synthase

Explanation: The correct answer is a) Succinate dehydrogenase. Riboflavin (Vitamin B2) is a precursor of FAD, required by succinate dehydrogenase. Deficiency leads to reduced FADH₂ production and decreased ATP yield, impairing energy metabolism. Answer is option a.

Topic: Carbohydrate Metabolism

Subtopic: Krebs Cycle (TCA Cycle)

Keyword Definitions:

• Krebs Cycle: Central aerobic pathway oxidizing acetyl-CoA to CO₂.

• ATP: Main cellular energy molecule generated in metabolism.

• NADH: Reduced coenzyme yielding ATP via oxidative phosphorylation.

• FADH₂: Reduced coenzyme yielding ATP through electron transport chain.

• Substrate level phosphorylation: Direct ATP or GTP generation in cycle.

• Oxidative phosphorylation: ATP synthesis using mitochondrial electron transport chain.

• Succinate dehydrogenase: Enzyme producing FADH₂ in Krebs cycle.

Lead Question - 2013

The number of ATPs generated in krebs cycle are ?

a) 12

b) 24

c) 15

d) 30

Explanation: The correct answer is a) 12. One turn of the Krebs cycle generates 3 NADH, 1 FADH₂, and 1 GTP. This corresponds to 9 ATP from NADH, 2 ATP from FADH₂, and 1 ATP from GTP, totaling 12 ATP equivalents per cycle. Answer is option a.

1) Guessed Question

Which enzyme of the Krebs cycle produces GTP directly?

a) Citrate synthase

b) Succinate thiokinase

c) Isocitrate dehydrogenase

d) Fumarase

Explanation: The correct answer is b) Succinate thiokinase. Also known as succinyl-CoA synthetase, this enzyme catalyzes substrate-level phosphorylation, producing GTP from GDP. This is the only step in the cycle generating ATP/GTP directly without oxidative phosphorylation. Answer is option b.

2) Guessed Question

A patient with thiamine deficiency has impaired Krebs cycle at which enzyme?

a) Succinate dehydrogenase

b) α-Ketoglutarate dehydrogenase

c) Fumarase

d) Malate dehydrogenase

Explanation: The correct answer is b) α-Ketoglutarate dehydrogenase. Thiamine (Vitamin B1) is a cofactor for α-ketoglutarate dehydrogenase. Its deficiency impairs ATP generation and causes lactic acidosis. Clinically, it presents as Beriberi and Wernicke-Korsakoff syndrome. Answer is option b.

3) Guessed Question

Which is the only enzyme of Krebs cycle embedded in the inner mitochondrial membrane?

a) Malate dehydrogenase

b) Succinate dehydrogenase

c) Aconitase

d) Isocitrate dehydrogenase

Explanation: The correct answer is b) Succinate dehydrogenase. This enzyme catalyzes the conversion of succinate to fumarate, producing FADH₂. It is unique because it is part of both the Krebs cycle and electron transport chain (Complex II). Answer is option b.

4) Guessed Question

How many NADH molecules are produced per acetyl-CoA in Krebs cycle?

a) 2

b) 3

c) 4

d) 1

Explanation: The correct answer is b) 3. Each acetyl-CoA oxidation in the Krebs cycle yields 3 NADH molecules through isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase steps. These NADH molecules generate 9 ATP via oxidative phosphorylation. Answer is option b.

5) Guessed Question

A patient with fumarase deficiency would show accumulation of which metabolite?

a) Succinate

b) Fumarate

c) Malate

d) Citrate

Explanation: The correct answer is b) Fumarate. Fumarase catalyzes the hydration of fumarate to malate. Deficiency leads to fumarate accumulation and impaired ATP generation. Clinically, this rare condition presents with encephalopathy, seizures, and developmental delay. Answer is option b.

6) Guessed Question

Which cofactor is required by succinate dehydrogenase?

a) Biotin

b) FAD

c) NAD+

d) Coenzyme A

Explanation: The correct answer is b) FAD. Succinate dehydrogenase requires flavin adenine dinucleotide (FAD) as a cofactor, producing FADH₂ when succinate is converted to fumarate. FAD is derived from riboflavin (Vitamin B2). Riboflavin deficiency impairs this step. Answer is option b.

7) Guessed Question

In myocardial ischemia, Krebs cycle activity decreases due to deficiency of?

a) Oxygen

b) Glucose

c) FADH₂

d) Acetyl-CoA

Explanation: The correct answer is a) Oxygen. Oxygen is the final electron acceptor in oxidative phosphorylation. In ischemia, lack of oxygen halts electron transport, reducing NAD+ and FAD availability, thereby inhibiting the Krebs cycle. This results in lactate accumulation and energy deficit. Answer is option a.

8) Guessed Question

How many FADH₂ molecules are generated in one turn of the Krebs cycle?

a) 1

b) 2

c) 3

d) 4

Explanation: The correct answer is a) 1. Succinate dehydrogenase produces 1 FADH₂ per acetyl-CoA oxidized in the Krebs cycle. This corresponds to 2 ATP equivalents through oxidative phosphorylation. Answer is option a.

9) Guessed Question

A patient with mitochondrial malate dehydrogenase defect would show impaired production of?

a) NADH

b) FADH₂

c) GTP

d) Acetyl-CoA

Explanation: The correct answer is a) NADH. Malate dehydrogenase converts malate to oxaloacetate, generating NADH. A defect decreases NADH production and ATP yield, impairing Krebs cycle progression. Clinically, energy deficiency leads to muscle weakness and neurologic symptoms. Answer is option a.

10) Guessed Question

Which of the following links glycolysis with the Krebs cycle?

a) Acetyl-CoA

b) Fumarate

c) Oxaloacetate

d) GTP

Explanation: The correct answer is a) Acetyl-CoA. Pyruvate from glycolysis is converted into acetyl-CoA by pyruvate dehydrogenase. Acetyl-CoA then enters the Krebs cycle. This step is essential for carbohydrate oxidation under aerobic conditions, linking glycolysis and the Krebs cycle. Answer is option a.

Topic: Carbohydrate Metabolism

Subtopic: Anaerobic Glycolysis

Keyword Definitions:

• Anaerobic glycolysis: Glucose breakdown without oxygen, producing lactate.

• RBCs: Lack mitochondria; depend entirely on anaerobic glycolysis for ATP.

• Muscles: Use anaerobic glycolysis during intense exercise when oxygen is limited.

• Brain: Primarily aerobic; anaerobic glycolysis not physiologically significant.

• Kidney: Utilizes aerobic glycolysis and oxidative phosphorylation.

• Lactate: End product of anaerobic glycolysis in humans.

• ATP: Cellular energy generated from glycolysis and oxidative pathways.

Lead Question - 2013

Anaerobic glycolysis occurs in all places except

a) Muscles

b) RBCs

c) Brain

d) Kidney

Explanation: The correct answer is d) Kidney. Anaerobic glycolysis occurs in tissues lacking sufficient oxygen or mitochondria, such as RBCs and exercising muscle. The brain mainly relies on aerobic metabolism. Kidney is primarily aerobic and does not significantly use anaerobic glycolysis. Thus, kidney is the exception. Answer is option d.

1) Guessed Question

Which is the main end product of anaerobic glycolysis in humans?

a) Ethanol

b) Lactate

c) Acetyl-CoA

d) Pyruvate

Explanation: The correct answer is b) Lactate. In anaerobic glycolysis, pyruvate is reduced to lactate by lactate dehydrogenase, regenerating NAD+ for glycolysis continuation. This process sustains ATP production in oxygen-poor conditions. Unlike yeast producing ethanol, humans generate lactate under anaerobic conditions. Answer is option b.

2) Guessed Question

A marathon runner develops muscle cramps due to anaerobic glycolysis. Which metabolite accumulates?

a) Lactate

b) Citrate

c) Acetyl-CoA

d) Oxaloacetate

Explanation: The correct answer is a) Lactate. During intense exercise, oxygen supply is insufficient, leading to anaerobic glycolysis. Lactate accumulates, lowering pH and causing muscle cramps and fatigue. This reversible process is relieved after rest and oxygen supply restoration. Answer is option a.

3) Guessed Question

Which enzyme catalyzes the conversion of pyruvate to lactate?

a) Pyruvate dehydrogenase

b) Lactate dehydrogenase

c) Pyruvate carboxylase

d) Malate dehydrogenase

Explanation: The correct answer is b) Lactate dehydrogenase. This enzyme reduces pyruvate to lactate, regenerating NAD+ needed for glycolysis. It is essential in anaerobic metabolism, especially in tissues like RBCs and exercising muscles. Elevated lactate dehydrogenase levels indicate tissue injury or hemolysis clinically. Answer is option b.

4) Guessed Question

Which tissue relies exclusively on anaerobic glycolysis for ATP?

a) Liver

b) Kidney

c) RBCs

d) Brain

Explanation: The correct answer is c) RBCs. Red blood cells lack mitochondria, hence cannot perform aerobic metabolism. They depend completely on anaerobic glycolysis for ATP generation. This makes glycolysis essential for RBC survival and function. Deficiency of glycolytic enzymes causes hemolytic anemia. Answer is option c.

5) Guessed Question

A patient in septic shock develops high blood lactate. The cause is:

a) Enhanced gluconeogenesis

b) Anaerobic glycolysis due to tissue hypoxia

c) Increased glycogenolysis

d) Inhibition of oxidative phosphorylation

Explanation: The correct answer is b) Anaerobic glycolysis due to tissue hypoxia. In septic shock, poor perfusion and hypoxia shift metabolism to anaerobic glycolysis, producing excess lactate and causing lactic acidosis. Elevated lactate is a marker of severity and poor prognosis. Answer is option b.

6) Guessed Question

Which organ clears most of the lactate produced by anaerobic glycolysis?

a) Heart

b) Brain

c) Liver

d) Kidney

Explanation: The correct answer is c) Liver. Lactate is transported to the liver and converted back to glucose via gluconeogenesis in the Cori cycle. This maintains glucose homeostasis and prevents severe lactic acidosis. The liver’s metabolic role is essential in clearing lactate from circulation. Answer is option c.

7) Guessed Question

A newborn presents with persistent lactic acidosis and developmental delay. Which enzyme deficiency is most likely?

a) Pyruvate carboxylase

b) Lactate dehydrogenase

c) Hexokinase

d) Enolase

Explanation: The correct answer is a) Pyruvate carboxylase. Deficiency blocks conversion of pyruvate to oxaloacetate, shunting pyruvate to lactate and causing lactic acidosis. Clinical features include neurologic impairment and failure to thrive. Dietary modifications and supportive therapy are management approaches. Answer is option a.

8) Guessed Question

Which laboratory test uses fluoride to inhibit anaerobic glycolysis in blood samples?

a) Urea test

b) Glucose estimation

c) Serum creatinine

d) Bilirubin levels

Explanation: The correct answer is b) Glucose estimation. Sodium fluoride inhibits enolase, preventing glycolysis in collected blood samples. This stabilizes glucose levels for accurate laboratory testing. Without inhibition, glycolysis would artificially lower glucose concentration during storage. Answer is option b.

9) Guessed Question

In ischemic heart tissue, anaerobic glycolysis leads to accumulation of which metabolite?

a) Acetyl-CoA

b) Lactate

c) Succinyl-CoA

d) Oxaloacetate

Explanation: The correct answer is b) Lactate. In ischemia, oxygen deficiency forces cardiac cells to depend on anaerobic glycolysis, producing lactate. This causes intracellular acidosis and contributes to myocardial injury. Clinical findings include elevated serum lactate in ischemic conditions. Answer is option b.

10) Guessed Question

Which condition shows increased anaerobic glycolysis even in presence of oxygen (Warburg effect)?

a) Diabetes mellitus

b) Cancer

c) Starvation

d) Hypothyroidism

Explanation: The correct answer is b) Cancer. Tumor cells preferentially use anaerobic glycolysis even with adequate oxygen, a phenomenon called the Warburg effect. This supports rapid proliferation and survival in hypoxic tumor microenvironments. It also forms the basis for PET imaging using glucose analogs. Answer is option b.

Topic: Carbohydrate Metabolism

Subtopic: Glycolysis

Keyword Definitions:

• Glycolysis: Pathway converting glucose to pyruvate with ATP production.

• Substrate level phosphorylation: Direct ATP generation from high-energy intermediates.

• Cancer cells: Depend on glycolysis (Warburg effect) for energy supply.

• NADPH: Reducing equivalent generated in pentose phosphate pathway, not glycolysis.

• Pyruvate kinase: Catalyzes final step of glycolysis, producing ATP.

• G3P dehydrogenase: Enzyme producing NADH during glycolysis.

• Two-carbon end product: Not true; glycolysis produces three-carbon pyruvate.

Lead Question - 2013

True about glycolysis are all except ?

a) Provide nutrition to cancer cells

b) Substrate level phosphorylation at pyruvate kinase

c) Two carbon end product is formed

d) NADPH is formed by glyceraldhyde-3-phosphate dehydrogenase

Explanation: The correct answer is d) NADPH is formed by glyceraldehyde-3-phosphate dehydrogenase. Glycolysis generates NADH, not NADPH. NADPH is produced in the pentose phosphate pathway. Glycolysis produces pyruvate (three-carbon), supports cancer metabolism, and includes substrate-level phosphorylation steps at phosphoglycerate kinase and pyruvate kinase. Thus, statement d is false. Answer is option d.

1) Guessed Question

Which glycolytic enzyme produces NADH?

a) Enolase

b) Aldolase

c) Glyceraldehyde-3-phosphate dehydrogenase

d) Pyruvate kinase

Explanation: The correct answer is c) Glyceraldehyde-3-phosphate dehydrogenase. This enzyme converts G3P to 1,3-bisphosphoglycerate, generating NADH. NADH later enters oxidative phosphorylation to produce ATP. Defects can impair glycolysis and energy yield. This makes G3P dehydrogenase a vital enzyme in energy metabolism. Answer is option c.

2) Guessed Question

A patient with pyruvate kinase deficiency will present with which clinical feature?

a) Hypoglycemia

b) Hemolytic anemia

c) Muscle weakness

d) Jaundice-free anemia

Explanation: The correct answer is b) Hemolytic anemia. Pyruvate kinase deficiency reduces ATP production in RBCs, impairing membrane stability, causing hemolysis. Clinically, patients show jaundice, splenomegaly, and anemia. Energy failure in RBCs explains the pathology. This condition is inherited and managed with supportive care. Answer is option b.

3) Guessed Question

Which step of glycolysis is inhibited by fluoride?

a) Pyruvate kinase

b) Enolase

c) Hexokinase

d) PFK-1

Explanation: The correct answer is b) Enolase. Fluoride inhibits enolase, preventing conversion of 2-phosphoglycerate to phosphoenolpyruvate. This is clinically significant for preserving blood glucose in fluoride tubes used for laboratory assays. Inhibition prevents glycolysis during sample storage. Answer is option b.

4) Guessed Question

Which glycolytic enzyme catalyzes an irreversible step?

a) Aldolase

b) Hexokinase

c) Phosphoglycerate kinase

d) Enolase

Explanation: The correct answer is b) Hexokinase. Hexokinase catalyzes the phosphorylation of glucose to glucose-6-phosphate, an irreversible step under cellular conditions. Such irreversible steps are key control points in glycolysis and must be bypassed in gluconeogenesis. Answer is option b.

5) Guessed Question

A neonate with severe lactic acidosis likely has a deficiency of which enzyme?

a) Pyruvate dehydrogenase

b) Enolase

c) Hexokinase

d) Triose phosphate isomerase

Explanation: The correct answer is a) Pyruvate dehydrogenase. Deficiency blocks conversion of pyruvate to acetyl-CoA, leading to lactic acidosis. Patients present with neurologic deficits, hypotonia, and developmental delay. Clinical management includes ketogenic diet to bypass glycolysis. Answer is option a.

6) Guessed Question

Which step of glycolysis directly generates ATP?

a) Pyruvate kinase

b) Enolase

c) Aldolase

d) Hexokinase

Explanation: The correct answer is a) Pyruvate kinase. Pyruvate kinase catalyzes substrate-level phosphorylation, producing ATP when phosphoenolpyruvate is converted to pyruvate. This is one of two ATP-generating steps in glycolysis, the other being phosphoglycerate kinase. This explains net ATP gain. Answer is option a.

7) Guessed Question

A patient on isoniazid therapy develops pellagra-like symptoms due to deficiency of which glycolytic cofactor?

a) Niacin

b) Riboflavin

c) Thiamine

d) Pyridoxine

Explanation: The correct answer is a) Niacin. Niacin deficiency reduces NAD+ availability, impairing glyceraldehyde-3-phosphate dehydrogenase activity in glycolysis. Clinically, pellagra manifests with diarrhea, dermatitis, and dementia. Isoniazid interferes with vitamin metabolism, aggravating deficiency. Answer is option a.

8) Guessed Question

Which glycolytic enzyme defect leads to hereditary hemolytic anemia other than pyruvate kinase deficiency?

a) Hexokinase

b) Phosphoglycerate kinase

c) PFK-1

d) Aldolase

Explanation: The correct answer is a) Hexokinase. Hexokinase deficiency decreases glycolytic ATP production in RBCs, causing hereditary hemolytic anemia. Clinical features include anemia, jaundice, and splenomegaly. Such enzyme deficiencies impair RBC survival due to their dependence on glycolysis for energy. Answer is option a.

9) Guessed Question

Which tissue relies exclusively on glycolysis for ATP generation?

a) Brain

b) Red blood cells

c) Heart

d) Liver

Explanation: The correct answer is b) Red blood cells. RBCs lack mitochondria, relying solely on glycolysis for ATP. This dependence explains their vulnerability to glycolytic enzyme defects. Brain also uses glycolysis but relies heavily on oxidative phosphorylation. RBCs are unique in complete glycolytic dependence. Answer is option b.

10) Guessed Question

A patient with sepsis develops high lactate levels. This is due to?

a) Increased aerobic glycolysis

b) Decreased oxygen supply causing anaerobic glycolysis

c) Increased gluconeogenesis

d) Inhibition of hexokinase

Explanation: The correct answer is b) Decreased oxygen supply causing anaerobic glycolysis. In sepsis, hypoperfusion and hypoxia stimulate anaerobic glycolysis, leading to lactate accumulation. Clinically, lactic acidosis is a poor prognostic sign in septic shock. Management requires oxygenation and hemodynamic support. Answer is option b.

Topic: Carbohydrate Metabolism

Subtopic: Glycolysis and Gluconeogenesis

Keyword Definitions:

• Glycolysis: Breakdown of glucose to pyruvate generating ATP.

• Gluconeogenesis: Formation of glucose from non-carbohydrate sources.

• Enzyme: Protein catalyst regulating biochemical reactions.

• Pyruvate kinase: Converts phosphoenolpyruvate to pyruvate.

• PFK (Phosphofructokinase): Key regulatory enzyme of glycolysis.

• Hexokinase: Converts glucose to glucose-6-phosphate.

• Phosphoglycerate kinase: Converts 1,3-BPG to 3-phosphoglycerate.

Lead Question - 2013

Which of the enzyme of glycolysis is a part of gluconeogenesis ?

a) Pyruvate kinase

b) PFK

c) Hexokinase

d) Phosphoglycerate kinase

Explanation: The correct answer is d) Phosphoglycerate kinase. This enzyme catalyzes a reversible step, functioning in both glycolysis and gluconeogenesis. Other listed enzymes catalyze irreversible steps specific to glycolysis. Thus, phosphoglycerate kinase is crucial in energy metabolism, highlighting shared pathways between glucose breakdown and synthesis. Answer is option d.

1) Guessed Question

Which glycolytic enzyme is bypassed in gluconeogenesis?

a) Phosphofructokinase

b) Aldolase

c) Enolase

d) Triose phosphate isomerase

Explanation: The correct answer is a) Phosphofructokinase. This irreversible step is bypassed by fructose-1,6-bisphosphatase in gluconeogenesis. Bypass reactions are necessary to overcome energy barriers of irreversible glycolytic steps. Understanding these bypasses is key in metabolic regulation and clinical disorders of glucose metabolism. Answer is option a.

2) Guessed Question

A patient with hypoglycemia after fasting likely has a deficiency in which gluconeogenic enzyme?

a) Glucose-6-phosphatase

b) Enolase

c) Phosphoglycerate mutase

d) Pyruvate kinase

Explanation: The correct answer is a) Glucose-6-phosphatase. Deficiency causes impaired gluconeogenesis and glycogenolysis, leading to fasting hypoglycemia, hepatomegaly, and lactic acidosis (Von Gierke’s disease). This enzyme is crucial for final glucose release into blood. Clinically, patients present with severe fasting intolerance. Answer is option a.

3) Guessed Question

Which cofactor is essential for pyruvate carboxylase in gluconeogenesis?

a) Thiamine

b) Biotin

c) Riboflavin

d) Niacin

Explanation: The correct answer is b) Biotin. Pyruvate carboxylase requires biotin as a coenzyme to catalyze the conversion of pyruvate to oxaloacetate in mitochondria. Biotin deficiency can impair gluconeogenesis, leading to hypoglycemia and metabolic disturbances. This highlights the importance of vitamins as enzyme cofactors. Answer is option b.

4) Guessed Question

Which of the following is an irreversible enzyme of glycolysis?

a) Hexokinase

b) Phosphoglycerate kinase

c) Enolase

d) Triose phosphate isomerase

Explanation: The correct answer is a) Hexokinase. Hexokinase catalyzes the phosphorylation of glucose to glucose-6-phosphate, an irreversible reaction under physiological conditions. Irreversible steps in glycolysis are key regulatory points that must be bypassed in gluconeogenesis to maintain metabolic balance. Answer is option a.

5) Guessed Question

A patient with alcohol intoxication is hypoglycemic. Which mechanism best explains this?

a) Increased gluconeogenesis

b) Inhibition of glycolysis

c) Increased NADH inhibits gluconeogenesis

d) Increased glycogen synthesis

Explanation: The correct answer is c) Increased NADH inhibits gluconeogenesis. Alcohol metabolism increases NADH/NAD+ ratio, diverting pyruvate to lactate and oxaloacetate to malate, preventing gluconeogenesis. This explains fasting hypoglycemia in alcoholics. Clinical management includes glucose supplementation and vitamin support. Answer is option c.

6) Guessed Question

Which enzyme connects gluconeogenesis and the urea cycle by generating fumarate?

a) Pyruvate carboxylase

b) PEP carboxykinase

c) Argininosuccinate lyase

d) Glucose-6-phosphatase

Explanation: The correct answer is c) Argininosuccinate lyase. This enzyme produces fumarate in the urea cycle, which enters gluconeogenesis via malate. Such metabolic interconnections integrate nitrogen and carbohydrate metabolism, essential for energy homeostasis and ammonia detoxification. Answer is option c.

7) Guessed Question

Which of the following steps is common to both glycolysis and gluconeogenesis?

a) Conversion of glucose to glucose-6-phosphate

b) Conversion of 1,3-BPG to 3-PG

c) Conversion of PEP to pyruvate

d) Conversion of fructose-6-phosphate to F-1,6-BP

Explanation: The correct answer is b) Conversion of 1,3-BPG to 3-PG. This reaction, catalyzed by phosphoglycerate kinase, is reversible and occurs in both glycolysis and gluconeogenesis. Shared steps conserve enzymes and resources, while bypass steps ensure directionality of pathways. Answer is option b.

8) Guessed Question

A neonate presents with severe lactic acidosis. Defect in which enzyme of gluconeogenesis is most likely?

a) Pyruvate carboxylase

b) Enolase

c) Aldolase

d) Triose phosphate isomerase

Explanation: The correct answer is a) Pyruvate carboxylase. Its deficiency leads to impaired conversion of pyruvate to oxaloacetate, blocking gluconeogenesis and causing lactic acidosis. Clinically, patients present with hypoglycemia, neurologic deficits, and failure to thrive. Treatment involves dietary modifications and supplements. Answer is option a.

9) Guessed Question

Which organ is the primary site of gluconeogenesis?

a) Muscle

b) Kidney

c) Liver

d) Adipose tissue

Explanation: The correct answer is c) Liver. The liver is the main site for gluconeogenesis, particularly during fasting. The kidney contributes during prolonged starvation. Other tissues lack the full complement of enzymes needed. This pathway maintains blood glucose homeostasis, crucial for brain and RBCs. Answer is option c.

10) Guessed Question

In uncontrolled diabetes, gluconeogenesis is stimulated mainly by which hormone?

a) Insulin

b) Glucagon

c) Epinephrine

d) Cortisol

Explanation: The correct answer is b) Glucagon. In diabetes, low insulin and high glucagon levels stimulate gluconeogenesis, worsening hyperglycemia. Glucagon activates key enzymes like PEP carboxykinase and fructose-1,6-bisphosphatase. This explains fasting hyperglycemia seen in type 1 diabetes mellitus. Answer is option b.

Topic: Metabolism
Subtopic: Gluconeogenesis

Keyword Definitions:
• Gluconeogenesis: Process of synthesizing glucose from non-carbohydrate sources.
• Lactate: End product of anaerobic glycolysis, used as substrate for gluconeogenesis.
• Pyruvate: Key intermediate formed from lactate and alanine.
• Alanine: Amino acid that can be converted to pyruvate via transamination.
• Cori Cycle: Cycle involving lactate transport from muscle to liver for gluconeogenesis.

Lead Question - 2013
Gluconeogenesis from lactate needs all except ?
a) Transport of lactate from muscle to liver
b) Conversion of lactate to pyruvate
c) Transamination of pyruvate to alanine
d) None of the above
Explanation: Transamination of pyruvate to alanine is not a necessary step for gluconeogenesis from lactate. The main requirement is lactate transport, conversion to pyruvate, and subsequent glucose synthesis via the Cori cycle. Answer: c) Transamination of pyruvate to alanine.

1) Which of the following cycles connects lactate metabolism in muscle with gluconeogenesis in liver?
a) Urea cycle
b) Cori cycle
c) TCA cycle
d) Glyoxylate cycle
Explanation: The Cori cycle describes the conversion of lactate from muscle to glucose in the liver. This prevents lactic acidosis and maintains glucose supply during anaerobic conditions. Answer: b) Cori cycle.

2) A patient with liver failure develops severe lactic acidosis after exercise. Which pathway is defective?
a) Glycolysis
b) Gluconeogenesis
c) Glycogenolysis
d) Pentose phosphate pathway
Explanation: In liver failure, gluconeogenesis is impaired, leading to defective utilization of lactate via the Cori cycle, causing lactic acidosis. Answer: b) Gluconeogenesis.

3) Which enzyme converts lactate to pyruvate in gluconeogenesis?
a) Lactate dehydrogenase
b) Pyruvate kinase
c) Pyruvate carboxylase
d) Alanine transaminase
Explanation: Lactate is oxidized to pyruvate by lactate dehydrogenase, using NAD⁺. This is the first step of lactate utilization in gluconeogenesis. Answer: a) Lactate dehydrogenase.

4) A marathon runner develops increased serum lactate after prolonged activity. Which tissue helps remove it through gluconeogenesis?
a) Brain
b) Liver
c) Muscle
d) RBC
Explanation: The liver removes lactate via gluconeogenesis during exercise, converting it into glucose, which is supplied back to muscles. Answer: b) Liver.

5) In gluconeogenesis, pyruvate is converted to oxaloacetate by:
a) Pyruvate carboxylase
b) Pyruvate kinase
c) Pyruvate dehydrogenase
d) Lactate dehydrogenase
Explanation: Pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate in mitochondria using biotin and ATP. Answer: a) Pyruvate carboxylase.

6) A patient with biotin deficiency is unable to utilize lactate for gluconeogenesis. Which enzyme is impaired?
a) Pyruvate carboxylase
b) PEP carboxykinase
c) Lactate dehydrogenase
d) Pyruvate kinase
Explanation: Pyruvate carboxylase requires biotin. Its deficiency impairs pyruvate to oxaloacetate conversion, blocking gluconeogenesis. Answer: a) Pyruvate carboxylase.

7) Which of the following substrates cannot be used for gluconeogenesis?
a) Glycerol
b) Fatty acids
c) Lactate
d) Alanine
Explanation: Most fatty acids (long-chain) cannot serve as substrates because acetyl-CoA cannot form glucose. Glycerol, lactate, and alanine are gluconeogenic. Answer: b) Fatty acids.

8) In Cori cycle, lactate is produced in:
a) RBC and muscle
b) Brain
c) Liver
d) Kidney
Explanation: Lactate is produced mainly in RBCs (no mitochondria) and active muscles. The liver converts this lactate to glucose. Answer: a) RBC and muscle.

9) Which coenzyme is required for lactate dehydrogenase reaction?
a) NAD⁺/NADH
b) FAD/FADH₂
c) TPP
d) Biotin
Explanation: Lactate dehydrogenase requires NAD⁺/NADH as coenzyme for reversible conversion of lactate and pyruvate. Answer: a) NAD⁺/NADH.

10) A patient with mitochondrial dysfunction cannot carry out pyruvate carboxylase reaction. Which process is impaired?
a) Glycolysis
b) Gluconeogenesis
c) Urea cycle
d) Glycogenolysis
Explanation: Pyruvate carboxylase is mitochondrial and essential for gluconeogenesis. Mitochondrial dysfunction blocks glucose synthesis from lactate. Answer: b) Gluconeogenesis.

Topic: Gluconeogenesis

Subtopic: Sites and Regulation

Keyword Definitions:

• Gluconeogenesis: Process of glucose synthesis from non-carbohydrate precursors.

• Liver: Primary site of gluconeogenesis, maintains blood glucose.

• Kidney: Secondary site of gluconeogenesis, especially in prolonged fasting.

• Muscle: Lacks glucose-6-phosphatase, cannot release glucose into blood.

• Gut: Intestinal cells may perform minor gluconeogenesis but not significant.

Lead Question - 2013

Gluconeogenesis occurs in all except?

a) Liver

b) Kidney

c) Gut

d) Muscle

Explanation:

Gluconeogenesis mainly occurs in the liver and kidney. The gut contributes minimally in fasting states. Muscle lacks glucose-6-phosphatase, hence cannot release free glucose into the blood. Therefore, gluconeogenesis does not occur in Muscle (Answer: d). This is a key differentiating feature between hepatic and muscle carbohydrate metabolism.

1) The first committed step in gluconeogenesis is catalyzed by:

a) Pyruvate carboxylase

b) PEP carboxykinase

c) Fructose-1,6-bisphosphatase

d) Glucose-6-phosphatase

Explanation:

The first committed step of gluconeogenesis is the conversion of pyruvate to oxaloacetate, catalyzed by pyruvate carboxylase, requiring biotin and ATP. This distinguishes it from glycolysis reversal. Thus, the correct answer is Pyruvate carboxylase (Answer: a). This regulatory step ensures glucose synthesis during fasting or starvation.

2) A patient with biotin deficiency will have impaired activity of:

a) Pyruvate carboxylase

b) Fructokinase

c) Glucokinase

d) Hexokinase

Explanation:

Biotin is a coenzyme required for carboxylation reactions, including pyruvate carboxylase. Its deficiency impairs gluconeogenesis, leading to hypoglycemia. Fructokinase, glucokinase, and hexokinase do not require biotin. Therefore, the enzyme affected is Pyruvate carboxylase (Answer: a). Clinical features include metabolic acidosis and neurological dysfunction.

3) Cori cycle links muscle glycolysis with hepatic gluconeogenesis by transporting:

a) Pyruvate

b) Lactate

c) Alanine

d) Glycerol

Explanation:

In the Cori cycle, lactate produced by anaerobic glycolysis in muscle is transported to the liver, where it undergoes gluconeogenesis to form glucose. The glucose returns to the muscle. Thus, the correct transported metabolite is Lactate (Answer: b). This cycle helps maintain blood glucose during exercise.

4) A patient with liver failure will have impaired gluconeogenesis leading to:

a) Hyperglycemia

b) Hypoglycemia

c) Hyperlipidemia

d) Gout

Explanation:

The liver is the primary site for gluconeogenesis. In liver failure, inability to generate glucose results in Hypoglycemia (Answer: b). This is especially severe during fasting. Hypoglycemia in such patients is a critical clinical feature requiring glucose infusion for stabilization.

5) Which amino acid is the major gluconeogenic precursor?

a) Alanine

b) Lysine

c) Leucine

d) Valine

Explanation:

Alanine, derived from muscle protein breakdown, is the most important gluconeogenic amino acid. It enters the glucose-alanine cycle, transporting nitrogen to the liver. Lysine and leucine are ketogenic, not gluconeogenic. Therefore, the major precursor is Alanine (Answer: a). This process becomes significant during fasting and starvation.

6) A patient with fasting hypoglycemia and lactic acidosis likely has deficiency of:

a) Glucokinase

b) Glucose-6-phosphatase

c) Hexokinase

d) Phosphofructokinase

Explanation:

Deficiency of glucose-6-phosphatase causes glycogen storage disease type I (von Gierke’s disease), presenting with hypoglycemia and lactic acidosis due to impaired gluconeogenesis and glycogenolysis. Hence, the enzyme deficient is Glucose-6-phosphatase (Answer: b). This condition also shows hepatomegaly and hyperuricemia.

7) Which step in gluconeogenesis bypasses pyruvate kinase?

a) Pyruvate → Oxaloacetate

b) Oxaloacetate → PEP

c) Fructose-1,6-bisphosphate → Fructose-6-phosphate

d) Glucose-6-phosphate → Glucose

Explanation:

Pyruvate kinase is bypassed by the two-step reaction catalyzed by pyruvate carboxylase and PEP carboxykinase. Together, they convert pyruvate into phosphoenolpyruvate. Thus, the bypass step is Pyruvate → Oxaloacetate and Oxaloacetate → PEP (Answer: a & b combined). This ensures irreversible steps of glycolysis are circumvented.

8) A malnourished alcoholic patient is given glucose infusion and develops lactic acidosis. The likely deficiency is:

a) Thiamine

b) Biotin

c) Vitamin C

d) Vitamin K

Explanation:

Alcoholics often develop thiamine deficiency. Without thiamine, pyruvate cannot enter the TCA cycle via PDH, leading to shunting of pyruvate to lactate, causing lactic acidosis. Therefore, the deficiency is Thiamine (Answer: a). Giving glucose without thiamine supplementation worsens this condition clinically (Wernicke encephalopathy risk).

9) Glycerol enters gluconeogenesis after conversion to:

a) Glycerol-3-phosphate

b) Dihydroxyacetone phosphate

c) Pyruvate

d) Acetyl-CoA

Explanation:

Glycerol released from lipolysis is converted to glycerol-3-phosphate by glycerol kinase, then oxidized to dihydroxyacetone phosphate, which enters gluconeogenesis. Thus, the correct intermediate is Dihydroxyacetone phosphate (Answer: b). This pathway becomes significant during prolonged fasting when triglycerides are mobilized.

10) A child with hepatomegaly, hypoglycemia, and increased blood lactate is suspected of having:

a) Von Gierke’s disease

b) McArdle’s disease

c) Pompe’s disease

d) Hers’ disease

Explanation:

Von Gierke’s disease (Type I glycogen storage disease) results from glucose-6-phosphatase deficiency. It presents with hepatomegaly, severe fasting hypoglycemia, lactic acidosis, and hyperuricemia. Thus, the correct answer is Von Gierke’s disease (Answer: a). Early diagnosis and dietary management are crucial to prevent complications.

11) The gluconeogenic enzyme absent in muscle is:

a) Pyruvate carboxylase

b) PEP carboxykinase

c) Fructose-1,6-bisphosphatase

d) Glucose-6-phosphatase

Explanation:

Muscle contains enzymes like pyruvate carboxylase, PEP carboxykinase, and fructose-1,6-bisphosphatase but lacks glucose-6-phosphatase. Hence, it cannot release free glucose into the bloodstream. Therefore, the absent enzyme is Glucose-6-phosphatase (Answer: d). This is why gluconeogenesis in muscle does not contribute to blood glucose regulation.

Topic: Carbohydrate Metabolism

Subtopic: Oxidative Decarboxylation of Pyruvate

Keyword Definitions:

• Thiamine: A coenzyme (TPP) needed for oxidative decarboxylation.

• Niacin: Vitamin B3, precursor of NAD⁺ used in redox reactions.

• Riboflavin: Vitamin B2, precursor of FAD, essential in oxidation reactions.

• Biotin: Vitamin B7, functions as a CO₂ carrier in carboxylation reactions.

• Pyruvate Dehydrogenase Complex: Multienzyme system converting pyruvate to acetyl-CoA.

Lead Question - 2013

Which of the following vitamins does not participate in oxidative decarboxylation of pyruvate to acetyl CoA?

a) Thiamine

b) Niacine

c) Riboflavin

d) Biotin

Explanation:

The oxidative decarboxylation of pyruvate requires thiamine (TPP), riboflavin (FAD), niacin (NAD⁺), and lipoic acid. Biotin, however, functions in carboxylation reactions and not in this pathway. Thus, the vitamin not involved is Biotin (Answer: d). This distinction is vital in metabolism understanding.

1) Pyruvate dehydrogenase complex requires which cofactor?

a) Biotin

b) Lipoic acid

c) Vitamin K

d) Vitamin C

Explanation:

Pyruvate dehydrogenase complex requires thiamine pyrophosphate, FAD, NAD⁺, coenzyme A, and lipoic acid as cofactors. Biotin and vitamins C, K are not part of this complex. Hence, the correct cofactor here is Lipoic acid (Answer: b). This is essential for acetyl-CoA generation from pyruvate.

2) A patient with thiamine deficiency will primarily show impaired:

a) Glycolysis

b) Pyruvate to Acetyl-CoA conversion

c) Glycogenolysis

d) Gluconeogenesis

Explanation:

Thiamine deficiency impairs pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, blocking acetyl-CoA production. Glycolysis itself continues normally. Thus, the impaired process is Pyruvate to Acetyl-CoA conversion (Answer: b). This explains neurological symptoms in thiamine deficiency such as Wernicke-Korsakoff syndrome.

3) Which vitamin deficiency mimics arsenic poisoning due to PDH inhibition?

a) Biotin

b) Niacin

c) Thiamine

d) Riboflavin

Explanation:

Both thiamine deficiency and arsenic toxicity inhibit pyruvate dehydrogenase complex, causing pyruvate accumulation and lactic acidosis. Therefore, the vitamin whose deficiency mimics arsenic poisoning is Thiamine (Answer: c). This association is clinically important in neurological manifestations and metabolic acidosis.

4) A child presents with lactic acidosis and neurological symptoms. Deficiency of which enzyme is suspected?

a) Glucokinase

b) Pyruvate carboxylase

c) Pyruvate dehydrogenase

d) Hexokinase

Explanation:

Defective pyruvate dehydrogenase prevents conversion of pyruvate to acetyl-CoA, leading to accumulation of lactate and neurological dysfunction. Thus, the deficient enzyme is Pyruvate dehydrogenase (Answer: c). This clinical presentation is consistent with PDH deficiency, a rare but serious metabolic disorder.

5) Which cofactor of PDH complex is derived from riboflavin?

a) NAD⁺

b) CoA

c) TPP

d) FAD

Explanation:

Riboflavin (Vitamin B2) is the precursor of FAD, a crucial cofactor in oxidative decarboxylation. TPP comes from thiamine, NAD⁺ from niacin, and CoA from pantothenic acid. Therefore, the riboflavin-derived cofactor is FAD (Answer: d). This role is essential in redox metabolism of carbohydrates.

6) Which vitamin deficiency will impair both PDH and α-ketoglutarate dehydrogenase complexes?

a) Thiamine

b) Biotin

c) Vitamin C

d) Vitamin K

Explanation:

Both PDH and α-ketoglutarate dehydrogenase require thiamine pyrophosphate (TPP) as a cofactor. Hence, thiamine deficiency affects both pathways, leading to reduced ATP production. Therefore, the correct answer is Thiamine (Answer: a). This explains neurological and cardiac symptoms seen in beriberi and Wernicke’s encephalopathy.

7) A patient with biotin deficiency will show impairment in which pathway?

a) Glycolysis

b) Gluconeogenesis

c) Oxidative decarboxylation

d) Glycogenolysis

Explanation:

Biotin is a coenzyme in carboxylation reactions such as pyruvate carboxylase in gluconeogenesis. Its deficiency causes impaired gluconeogenesis and hypoglycemia. Therefore, the affected pathway is Gluconeogenesis (Answer: b). This distinguishes biotin’s role from vitamins involved in oxidative decarboxylation of pyruvate.

8) Which of the following is not a cofactor of pyruvate dehydrogenase complex?

a) NAD⁺

b) FAD

c) Biotin

d) Lipoic acid

Explanation:

The pyruvate dehydrogenase complex requires TPP, FAD, NAD⁺, CoA, and lipoic acid. Biotin is not involved in this process but functions in carboxylation reactions. Hence, the correct answer is Biotin (Answer: c). This clarifies the specific cofactor requirements of PDH complex in energy metabolism.

9) Which clinical condition results from PDH complex deficiency?

a) Hypoglycemia

b) Lactic acidosis

c) Hyperammonemia

d) Gout

Explanation:

A deficiency of PDH complex leads to accumulation of pyruvate, which is shunted to lactate, causing lactic acidosis. This is a hallmark clinical feature. Hence, the condition caused is Lactic acidosis (Answer: b). This explains neurological deficits and metabolic disturbances in patients with PDH deficiency.

10) A newborn with failure to thrive and lactic acidosis most likely has deficiency of:

a) Pyruvate carboxylase

b) Pyruvate dehydrogenase

c) Fructokinase

d) Aldolase B

Explanation:

Deficiency of pyruvate dehydrogenase results in lactic acidosis and poor energy production, leading to failure to thrive. Pyruvate carboxylase deficiency causes hypoglycemia, while aldolase B affects fructose metabolism. Thus, the newborn’s condition suggests Pyruvate dehydrogenase deficiency (Answer: b). This highlights the clinical importance of PDH in metabolism.

11) Which vitamin-derived cofactor is common to PDH and transketolase?

a) Biotin

b) Riboflavin

c) Thiamine

d) Niacin

Explanation:

Both PDH complex and transketolase require thiamine pyrophosphate (TPP) derived from thiamine. This forms the basis of the thiamine deficiency test using erythrocyte transketolase activity. Therefore, the common vitamin-derived cofactor is Thiamine (Answer: c). This illustrates overlapping roles of vitamins in metabolic pathways.

Topic: Gluconeogenesis 

Subtopic: Substrates of Gluconeogenesis 

Keyword Definitions: 

 • Gluconeogenesis: Process of synthesizing glucose from non-carbohydrate precursors, mainly in liver and kidney. 

 • Oleate: A long-chain fatty acid, provides energy but cannot yield net glucose. 

 • Succinate: TCA cycle intermediate that contributes carbon skeletons for gluconeogenesis. 

 • Glutamate: Amino acid converted to α-ketoglutarate, entering gluconeogenesis. 

 • Aspartate: Amino acid feeding oxaloacetate, a gluconeogenic substrate.

Lead Question - 2013

All are used in gluconeogenesis except ?

a) Oleate

b) Succinate

c) Glutamate

d) Aspartate

Explanation: Gluconeogenesis requires carbon skeletons from amino acids and TCA intermediates. Succinate, Glutamate, and Aspartate contribute carbons for glucose synthesis. Oleate, a pure fatty acid, undergoes β-oxidation to yield acetyl-CoA, which cannot be converted to glucose due to irreversible pyruvate dehydrogenase step. Thus, oleate is not used.

1) Which amino acid directly enters gluconeogenesis via conversion to oxaloacetate?

a) Alanine

b) Aspartate

c) Glutamate

d) Serine

Explanation: Aspartate directly transaminates to oxaloacetate, a crucial substrate for gluconeogenesis. This allows efficient glucose production in fasting state, especially in liver. Thus, aspartate is classified as a glucogenic amino acid.

2) A child with fatty acid oxidation disorder develops hypoglycemia. Why?

a) Ketone overproduction

b) Lack of NADH for gluconeogenesis

c) Excessive glycogen breakdown

d) Hyperactive PDH complex

Explanation: In fatty acid oxidation defects, NADH generation is impaired, reducing energy for gluconeogenesis. This leads to fasting hypoglycemia and low ketone production, a hallmark of these disorders.

3) Which of the following is a purely ketogenic amino acid?

a) Glutamate

b) Lysine

c) Aspartate

d) Alanine

Explanation: Lysine is purely ketogenic and cannot yield glucose. It is converted to acetyl-CoA, which enters ketogenesis. Glucogenic amino acids like alanine, aspartate, and glutamate provide carbon skeletons for gluconeogenesis.

4) Which pathway supplies glycerol for gluconeogenesis?

a) Lipolysis

b) Glycolysis

c) Pentose phosphate pathway

d) TCA cycle

Explanation: Lipolysis of triglycerides releases glycerol, which is converted to dihydroxyacetone phosphate (DHAP), a gluconeogenic substrate. This process is crucial during prolonged fasting, when glycerol becomes a significant glucose source.

5) A patient with PDH deficiency cannot use pyruvate for acetyl-CoA formation. Pyruvate is instead shunted to?

a) Oxaloacetate

b) Fumarate

c) Citrate

d) Malate

Explanation: In PDH deficiency, pyruvate cannot convert to acetyl-CoA. Instead, it is carboxylated to oxaloacetate via pyruvate carboxylase, fueling gluconeogenesis. This compensatory mechanism helps prevent hypoglycemia, though lactic acidosis is common.

6) Which hormone stimulates gluconeogenesis most strongly?

a) Insulin

b) Glucagon

c) Growth hormone

d) Thyroxine

Explanation: Glucagon is the primary stimulator of gluconeogenesis. It activates cAMP and increases expression of gluconeogenic enzymes such as PEP carboxykinase, ensuring glucose availability during fasting.

7) Why can odd-chain fatty acids contribute to gluconeogenesis?

a) They produce acetyl-CoA

b) They produce succinyl-CoA

c) They produce citrate

d) They produce oxaloacetate

Explanation: Odd-chain fatty acids yield succinyl-CoA, which enters the TCA cycle and serves as a gluconeogenic substrate. In contrast, even-chain fatty acids yield only acetyl-CoA, which cannot produce net glucose.

8) A patient with chronic alcoholism has impaired gluconeogenesis due to excess NADH. Which intermediate is reduced to lactate?

a) Malate

b) Pyruvate

c) Oxaloacetate

d) Acetyl-CoA

Explanation: Excess NADH in alcoholism drives conversion of pyruvate to lactate, blocking its entry into gluconeogenesis. This results in lactic acidosis and hypoglycemia.

9) Which enzyme catalyzes the final step of gluconeogenesis, releasing free glucose?

a) Pyruvate carboxylase

b) PEP carboxykinase

c) Glucose-6-phosphatase

d) Fructose-1,6-bisphosphatase

Explanation: Glucose-6-phosphatase catalyzes the last step of gluconeogenesis, converting glucose-6-phosphate to free glucose. This enzyme is present in the liver and kidney, but absent in muscle, preventing glucose release from muscle glycogen.

10) In gluconeogenesis, which enzyme bypasses phosphofructokinase-1?

a) Pyruvate carboxylase

b) Glucose-6-phosphatase

c) Fructose-1,6-bisphosphatase

d) PEP carboxykinase

Explanation: Fructose-1,6-bisphosphatase bypasses PFK-1, converting fructose-1,6-bisphosphate to fructose-6-phosphate. This is a key regulatory step, stimulated by ATP and inhibited by AMP and fructose-2,6-bisphosphate.

Topic: Metabolic Regulation in Fasting 

Subtopic: Enzyme Activity during Starvation 

Keyword Definitions: 

 • Fasting/Starvation: A metabolic state where the body shifts from glucose utilization to fat and ketone metabolism. 

 • Hexokinase: Enzyme catalyzing phosphorylation of glucose in glycolysis. 

 • Glucokinase: Liver enzyme with high Km for glucose, active postprandially. 

 • PDH (Pyruvate Dehydrogenase): Converts pyruvate to acetyl-CoA for TCA cycle. 

 • Pyruvate Kinase: Enzyme catalyzing conversion of phosphoenolpyruvate to pyruvate in glycolysis.

Lead Question - 2013

All of the following are inhibited during fasting/ starvation, except ?

a) Hexokinase

b) Glucokinase

c) PDH

d) Pyruvate kinase

Explanation: During fasting, glycolytic and oxidative enzymes such as Glucokinase, Pyruvate kinase, and PDH are inhibited to conserve glucose. Hexokinase, however, continues functioning in essential tissues like the brain and red blood cells. Hence, Hexokinase is not inhibited, ensuring glucose utilization in critical organs.

1) In fasting state, which hormone primarily regulates suppression of glycolytic enzymes?

a) Insulin

b) Glucagon