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: 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: 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: 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: 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.
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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: 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: 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: 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: 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.