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: 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: 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.
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.
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.
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: 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: 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: 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.
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)