Carbohydrate Metabolism (Glycolysis, Gluconeogenesis, Glycogen, HMP Shunt) MCQs

Biochemistry · 82 free questions with answers & explanations.

1. A 6-month-old infant presents with hypoglycemia, hepatomegaly, and lactic acidosis after fasting. Liver biopsy shows marked glycogen accumulation. Enzyme assay reveals deficiency of glucose-6-phosphatase. Which metabolic process is PRIMARILY impaired in this child?
2. During strenuous anaerobic exercise, the pyruvate produced by glycolysis is preferentially converted to lactate in skeletal muscle. The primary biochemical purpose of this conversion is to:
3. A newborn male is noted to have hemolytic anemia, jaundice, and splenomegaly. Red cell enzyme assay shows markedly reduced activity of phosphofructokinase-1 (PFK-1). Which best explains why PFK-1 deficiency causes hemolysis?
4. In the fed state, glucose entering hepatocytes is phosphorylated to glucose-6-phosphate and then converted to glucose-1-phosphate, which enters glycogen synthesis. The enzyme that converts glucose-1-phosphate to UDP-glucose for glycogen synthesis is:
5. A 3-year-old child with recurrent infections and hemolytic anemia is found to have reduced neutrophil oxidative burst. Peripheral smear shows Heinz bodies. Which enzyme deficiency most likely explains both findings?
6. A 3-year-old child presents with hypoglycemia, hepatomegaly, and lactic acidosis after overnight fasting. Liver biopsy shows massive glycogen accumulation. Enzyme assay reveals absent glucose-6-phosphatase activity. Which additional metabolic abnormality would be expected in this patient?
7. During a prolonged fast of 48 hours, the liver relies heavily on gluconeogenesis. Which regulatory mechanism specifically prevents simultaneous futile cycling between pyruvate kinase and phosphoenolpyruvate carboxykinase (PEPCK) during this state?
8. A neonate develops hemolytic anemia, jaundice, and cataracts within days of starting breastfeeding. Urine reducing substance test is positive but glucose oxidase test is negative. The enzyme most likely deficient in this infant catalyzes which reaction?
9. In the HMP shunt (pentose phosphate pathway), the non-oxidative phase is catalyzed by transketolase and transaldolase. A patient with chronic alcoholism and thiamine deficiency would show impaired activity of transketolase because thiamine pyrophosphate (TPP) is an essential cofactor. Which ADDITIONAL TPP-dependent enzyme would be simultaneously impaired, contributing to neurological symptoms?
10. A muscle biopsy from a patient with exercise intolerance and myoglobinuria after vigorous activity shows absent myophosphorylase on histochemical staining (McArdle disease). Serum lactate fails to rise during ischemic forearm exercise, but ammonia rises appropriately. This dissociation occurs because:
11. A neonate presents on day 3 of life with profound hypoglycemia, lactic acidosis, and hepatomegaly. Liver biopsy shows increased glycogen with normal structure. Enzyme assay reveals absent glucose-6-phosphatase activity. Which metabolic process is primarily blocked, causing both fasting hypoglycemia AND post-glucagon failure to raise blood glucose?
12. Phosphofructokinase-1 (PFK-1), the key regulatory enzyme of glycolysis, is allosterically inhibited by citrate. What is the metabolic rationale for this inhibition?
13. A patient with hemolytic anemia shows no Heinz bodies, normal G6PD activity, and normal hemoglobin electrophoresis. Erythrocyte pyruvate kinase (PK) activity is markedly reduced. Which specific metabolic consequence explains the hemolysis in PK deficiency?
14. During fasting, which enzyme of gluconeogenesis is transcriptionally upregulated by glucagon via CREB-mediated gene expression, and simultaneously post-translationally activated by acetyl-CoA?
15. A 6-month-old infant presents with recurrent hypoglycemia, failure to thrive, and cataracts. Urine shows reducing substance (non-glucose). The enzyme deficient in this condition also provides precursors for glycoprotein and glycolipid synthesis. Which enzyme is deficient?
16. In the HMP (pentose phosphate) shunt, glucose-6-phosphate dehydrogenase catalyzes the rate-limiting step. Which metabolite most potently inhibits this enzyme, and what is the physiological consequence in oxidative stress?
17. A patient with McArdle disease (GSD Type V, muscle phosphorylase deficiency) experiences painful cramps during exercise with no rise in venous lactate after forearm exercise test. Which feature best distinguishes this from GSD Type III (Cori disease, debranching enzyme deficiency)?
18. A 3-month-old infant presents with hypoglycemia, hepatomegaly, and lactic acidosis that worsens after glucose administration. Liver biopsy shows glycogen accumulation. Enzyme assay reveals deficiency of glucose-6-phosphatase. Which gluconeogenic substrate would be LEAST helpful in managing hypoglycemia in this patient?
19. Phosphofructokinase-1 (PFK-1) is allosterically regulated by multiple effectors. A newly synthesized competitive inhibitor mimics ATP binding at the allosteric site rather than the substrate site. Which statement about this inhibitor's effect on PFK-1 kinetics is MOST accurate?
20. A 6-month-old infant has progressive hepatosplenomegaly, failure to thrive, and cataracts. Reducing substances are found in urine but glucose oxidase test is negative. RBC enzyme assay confirms galactose-1-phosphate uridylyltransferase deficiency. Which metabolite is directly responsible for cataracts in this disorder?
21. In the HMP shunt, transketolase requires thiamine pyrophosphate (TPP) as cofactor and transfers 2-carbon units. In thiamine deficiency, which specific reaction step in the non-oxidative phase of the pentose phosphate pathway is PRIMARILY impaired?
22. A neonate develops severe hypoglycemia unresponsive to glucagon. Glycerol infusion corrects blood glucose transiently. Liver biopsy shows reduced but not absent glycogen stores. Enzyme studies identify a defect in the muscle-specific phosphorylase b kinase alpha subunit gene (PHKA1). What would be the expected finding in the RED BLOOD CELLS of this patient?
23. A neonate presents on day 3 with lethargy, poor feeding, and profound hypoglycemia. Liver biopsy reveals massive hepatomegaly with glycogen accumulation. Enzyme assay shows absent glucose-6-phosphatase activity. Which of the following best explains why glucagon administration fails to correct hypoglycemia in this infant?
24. During prolonged fasting, hepatic gluconeogenesis is maximally active. Which allosteric effector directly inhibits pyruvate kinase (L isoform) to prevent futile cycling between PEP and pyruvate?
25. A male infant develops hemolytic anemia, cataracts, and progressive intellectual disability. Urine reducing substance (Clinitest) is positive but glucose oxidase dipstick is negative. Erythrocyte enzyme assay shows absent galactose-1-phosphate uridylyltransferase (GALT). Which metabolite accumulates in the lens and causes cataracts in this condition?
26. A 2-year-old boy presents with episodes of hypoglycemia triggered by fasting, hepatomegaly, and lactic acidosis. Glucagon fails to raise blood glucose. Fasting plasma reveals elevated lactate, pyruvate, alanine, and uric acid. Liver biopsy shows glycogen AND fat accumulation. The enzyme deficiency is:
27. In the HMP shunt, oxidative phase, which enzyme catalyzes the committed, rate-limiting, and NADPH-producing first step, and what is its key allosteric inhibitor?
28. A 3-month-old infant presents with hepatomegaly, hypoglycemia, and elevated blood lactate after fasting. Liver biopsy shows glycogen accumulation. Enzyme activity assay reveals deficiency of glucose-6-phosphatase. Which biochemical consequence directly explains the fasting hypoglycemia in this condition?
29. During vigorous anaerobic exercise, skeletal muscle lactic acid is released into circulation. In the liver, lactate is converted back to glucose via the Cori cycle. Which enzyme catalyzes the rate-limiting committed step of hepatic gluconeogenesis from oxaloacetate?
30. A newborn male presents with hemolytic anemia and neonatal jaundice. No Heinz bodies are seen on peripheral smear. Enzyme assay confirms pyruvate kinase deficiency. What is the direct metabolic consequence that leads to red cell hemolysis in this condition?
31. In the HMP (pentose phosphate) pathway, glucose-6-phosphate dehydrogenase produces NADPH. Which step of the non-oxidative phase regenerates fructose-6-phosphate and glyceraldehyde-3-phosphate, and what enzyme primarily catalyzes these reversible interconversions?
32. Fructose-2,6-bisphosphate (F-2,6-BP) is the most potent allosteric activator of phosphofructokinase-1 (PFK-1). The enzyme that synthesizes F-2,6-BP is bifunctional (PFK-2/FBPase-2). When glucagon acts on the liver, what happens to F-2,6-BP levels and the resultant metabolic effect?
33. A 3-month-old infant presents with severe hypoglycemia after fasting, hepatomegaly, and lactic acidosis. Liver biopsy shows glycogen accumulation. Enzyme assay reveals absent glucose-6-phosphatase activity. Which metabolic consequence directly explains the lactic acidosis in this condition?
34. Fructose-1,6-bisphosphatase deficiency is identified in a neonate with recurrent hypoglycemia and lactic acidosis precipitated by fasting. Which specific gluconeogenic step is blocked, and why does gluconeogenesis from lactate fail while gluconeogenesis from galactose remains unaffected?
35. Phosphofructokinase-1 (PFK-1) is activated by AMP, ADP, fructose-2,6-bisphosphate, and inhibited by ATP, citrate, and H+. During intense exercise, glycolysis accelerates paradoxically despite a transient fall in pH. Which mechanism overrides the H+-mediated inhibition of PFK-1?
36. A male neonate develops progressive hemolytic anemia with red cell inclusions (Heinz bodies) and cyanosis unresponsive to methylene blue. NADPH levels in red cells are markedly reduced. Newborn screening for which enzyme deficiency should be prioritized?
37. Glycogen debranching enzyme has two catalytic activities essential for complete glycogenolysis. In GSD type III (Cori disease), which two enzymatic functions are absent, and what accumulates in the tissue?
38. A 6-month-old infant presents with episodic hypoglycemia, hepatomegaly, and failure to thrive. Liver biopsy shows massive glycogen accumulation with normal glycogen structure. Enzyme assay reveals absent glucose-6-phosphatase activity. Which metabolic pathway is additionally impaired in this condition beyond glycogenolysis?
39. In fructose-1,6-bisphosphatase deficiency, hypoglycemia characteristically occurs after ingestion of which substrate?
40. Phosphoglucose isomerase (PGI) deficiency presents with hemolytic anemia without hypoglycemia. The hemolysis occurs because RBCs depend exclusively on which pathway for ATP, and PGI deficiency traps glucose-6-phosphate upstream?
41. The allosteric activator fructose-2,6-bisphosphate (F2,6-BP) exerts its principal effect on which pair of enzymes in liver carbohydrate metabolism?
42. A 3-year-old presents with fasting hypoglycemia, ketosis, and elevated plasma lactate. Glucagon fails to raise blood glucose. Electron microscopy of liver shows depleted glycogen stores. Which enzyme defect is most consistent?
43. In the HMP shunt (pentose phosphate pathway), Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme. Its product NADPH is MOST critical in erythrocytes for which specific reaction?
44. A 3-day-old neonate presents with severe hypoglycemia, hepatomegaly, and lactic acidosis. Fructose-1,6-bisphosphatase assay in liver tissue shows markedly reduced activity. Glucagon infusion fails to raise blood glucose. Which metabolic pathway is primarily blocked?
45. Pyruvate kinase deficiency causes chronic haemolytic anaemia in adults. The biochemical basis for haemolysis in this enzyme deficiency is primarily:
46. In gluconeogenesis, the transport of oxaloacetate from mitochondria to cytosol is required because PEPCK is primarily cytosolic. Oxaloacetate itself cannot cross the inner mitochondrial membrane. The molecule in which oxaloacetate carbon equivalents are exported to the cytosol is:
47. Transketolase activity in erythrocytes is used as a functional test for which vitamin deficiency, and what is the basis for this test?
48. Fructose-1,6-bisphosphatase (FBPase-1) deficiency is a disorder of gluconeogenesis. During prolonged fasting or high-fructose intake in an affected infant, which metabolite accumulates and causes lactic acidosis?
49. In the HMP shunt (pentose phosphate pathway), glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme. Which metabolite serves as both the allosteric activator of glucose-6-phosphate dehydrogenase and the immediate oxidising cosubstrate?
50. Von Gierke disease (GSD type 1a) is due to glucose-6-phosphatase deficiency. Which hepatic metabolic consequences are DIRECTLY attributable to the accumulation of glucose-6-phosphate?
51. In glucose-6-phosphatase deficiency (Von Gierke's disease/GSD Type 1), which metabolic pathways are SECONDARILY affected, and what clinical features result?
52. In galactosemia (classical, GALT deficiency), galactose-1-phosphate accumulates. The MOST dangerous acute complication and the biochemical explanation for cataracts in untreated patients are:
53. The regulation of phosphofructokinase-1 (PFK-1) is critical for glycolytic flux. Which combination of effectors represents a physiological 'fed state' activation profile of PFK-1?
54. A patient with glucose-6-phosphatase deficiency (von Gierke disease) presents with severe fasting hypoglycemia. Why does fasting hypoglycemia occur but postprandial hyperglycemia does not?
55. In erythrocytes, the HMP shunt (pentose phosphate pathway) is essential for protecting against oxidative hemolysis. G6PD deficiency leads to hemolysis when triggered by oxidative stress. Which molecule directly protects hemoglobin from oxidative denaturation in normal RBCs?
56. Fructose-2,6-bisphosphate (F-2,6-BP) is a potent allosteric regulator of hepatic carbohydrate metabolism. What is the effect of elevated F-2,6-BP on gluconeogenesis?
57. Fructose-2,6-bisphosphate (F-2,6-BP) is a potent allosteric regulator of glycolysis and gluconeogenesis. In the FED state, insulin promotes F-2,6-BP synthesis by:
58. Von Gierke disease (GSD type I) involves glucose-6-phosphatase deficiency. Which clinical biochemistry finding is MOST characteristic?
59. In the HMP shunt, the IRREVERSIBLE oxidative phase generates NADPH and ribulose-5-phosphate. The enzyme that regenerates glucose-6-phosphate from the non-oxidative phase intermediates is:
60. Glucose-6-phosphatase is absent in skeletal muscle and brain. This means that glycogen breakdown in these tissues cannot release free glucose into the blood because:
61. In the HMP shunt (pentose phosphate pathway), the oxidative phase generates NADPH and ribose-5-phosphate. A patient with G6PD deficiency is given primaquine. Haemolysis occurs because:
62. A newborn presents on day 2 with vomiting and jaundice after breastfeeding. Urine reducing substances are positive but glucose oxidase test is negative. Diagnosis is galactosemia (GALT deficiency). The toxic metabolite responsible for cataracts in this condition is:
63. Fructose-1,6-bisphosphatase (FBPase-1) is the key regulated enzyme of gluconeogenesis. It is allosterically inhibited by fructose-2,6-bisphosphate (F-2,6-BP). F-2,6-BP levels are controlled by which bifunctional enzyme, and how does glucagon regulate this?
64. Glucose-6-phosphate dehydrogenase (G6PD) deficiency renders RBCs unable to maintain adequate NADPH levels. Which of the following drugs is SAFE to use in G6PD-deficient patients?
65. Pyruvate kinase (PK) deficiency causes chronic haemolytic anaemia. The SPECIFIC biochemical mechanism of red cell destruction in PK deficiency involves:
66. Glucose-6-phosphatase is absent in the liver and kidney in Type Ia glycogen storage disease (von Gierke's disease). A patient with this condition develops SEVERE hypoglycaemia between meals. The metabolic consequence that explains the inability to maintain blood glucose is:
67. The pentose phosphate pathway (PPP) is activated in response to oxidative stress. The REGULATORY enzyme controlling flux through the PPP is inhibited by its own product. Which substrate-product pair is involved in this feedback regulation?
68. Fructose-2,6-bisphosphate (F2,6BP) is a key allosteric regulator of glycolysis and gluconeogenesis. In the fasted state, glucagon increases cAMP and activates PKA. PKA phosphorylates the bifunctional enzyme PFK-2/FBPase-2. What is the net metabolic consequence?
69. Glycogen storage disease type III (Cori disease) is caused by debranching enzyme (amylo-1,6-glucosidase/4-alpha-glucanotransferase) deficiency. Glycogen structure in Cori disease differs from that in McArdle disease (GSD V) in that:
70. Galactose-1-phosphate uridyltransferase (GALT) deficiency causes classic galactosemia. The mechanism of cataracts in galactosemia is DIFFERENT from that in galactokinase deficiency because in GALT deficiency:
71. A newborn presents with lactic acidosis, hypoglycemia, hepatomegaly, and elevated blood lactate after feeding. Erythrocyte transketolase and glucose tolerance test are normal. Liver biopsy shows glycogen accumulation. The enzyme defect is MOST likely in:
72. Fructose-1,6-bisphosphatase deficiency presents in infants with hypoglycaemia, lactic acidosis, and hepatomegaly precipitated by fasting or fever. The enzyme catalyses which irreversible gluconeogenic step?
73. Sorbitol pathway activity increases in hyperglycaemia. Which clinical complication is most directly linked to sorbitol accumulation in tissues lacking sorbitol dehydrogenase (lens, nerve, kidney, retina)?
74. Von Gierke disease (GSD type Ia) is caused by glucose-6-phosphatase deficiency. The enzyme complex (G6Pase) is located on the luminal face of the ER membrane. Clinically, which laboratory finding is characteristic of this condition?
75. Pyruvate carboxylase, the first step of hepatic gluconeogenesis, is allosterically activated by:
76. Von Gierke disease (GSD type I) is due to glucose-6-phosphatase deficiency. Which clinical finding best distinguishes it from other glycogen storage diseases?
77. Fructose-2,6-bisphosphate (F-2,6-BP) is the most potent allosteric activator of PFK-1. Glucagon decreases hepatic F-2,6-BP by:
78. A 2-day-old neonate develops jaundice, hepatomegaly, and cataracts. Urine reducing substances are positive but glucose oxidase test is negative, indicating a non-glucose reducing sugar in urine. The infant was being breastfed. Deficiency of which enzyme is most likely responsible?
79. During intense muscle exercise, glucose is catabolized anaerobically. The regeneration of NAD+ in the cytoplasm is essential for glycolysis to continue. Which reaction specifically regenerates cytoplasmic NAD+ under anaerobic conditions in skeletal muscle?
80. A 6-month-old infant presents with hepatomegaly, fasting hypoglycemia, and failure to thrive. Liver biopsy shows massive glycogen accumulation. Biochemical analysis reveals absent glucose-6-phosphatase activity. In this condition, which metabolic pathway is specifically blocked that explains the inability to maintain fasting blood glucose?
81. The pentose phosphate pathway (PPP) is crucial for erythrocyte survival. In a patient with G6PD deficiency exposed to an oxidant drug, erythrocytes undergo hemolysis. Which molecule, normally maintained in its reduced form by the PPP, is directly responsible for protecting erythrocyte membranes from oxidative damage?
82. A patient with type 2 diabetes mellitus is started on metformin, which activates AMP-activated protein kinase (AMPK). As a direct consequence of AMPK activation, which of the following enzymes is phosphorylated and inactivated, thereby reducing hepatic glucose output?