Gluconeogenesis – pathway MCQs With Answer is a focused review designed for B. Pharm students to master the biochemical pathway of glucose synthesis. This concise, keyword-rich introduction covers essential concepts: substrates (lactate, alanine, glycerol), key enzymes (pyruvate carboxylase, PEPCK, fructose-1,6-bisphosphatase, glucose-6-phosphatase), regulation by hormones (insulin, glucagon) and allosteric effectors, tissue specificity (liver, kidney), energetic cost, and clinical relevance (diabetes, metabolic disorders, drug effects such as metformin). Practice with pathway MCQs improves retention, exam performance, and application to pharmacology. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which organ is the primary site of gluconeogenesis in humans?
- Liver
- Brain
- Skeletal muscle
- Adipose tissue
Correct Answer: Liver
Q2. Which enzyme catalyzes the conversion of pyruvate to oxaloacetate in gluconeogenesis?
- Pyruvate kinase
- Pyruvate carboxylase
- PEP carboxykinase (PEPCK)
- Malate dehydrogenase
Correct Answer: Pyruvate carboxylase
Q3. Which cofactor is required for pyruvate carboxylase activity?
- Biotin
- Thiamine pyrophosphate
- NAD+
- FAD
Correct Answer: Biotin
Q4. Which enzyme bypasses the irreversible phosphofructokinase-1 step during gluconeogenesis?
- Fructose-1,6-bisphosphatase (FBPase-1)
- Hexokinase
- Glucose-6-phosphatase
- Aldolase
Correct Answer: Fructose-1,6-bisphosphatase (FBPase-1)
Q5. What is the immediate product of PEPCK during gluconeogenesis?
- Oxaloacetate
- Phosphoenolpyruvate (PEP)
- 3-Phosphoglycerate
- Glyceraldehyde-3-phosphate
Correct Answer: Phosphoenolpyruvate (PEP)
Q6. Which substrate is NOT a major precursor for gluconeogenesis in the liver?
- Lactate
- Alanine
- Glycerol
- Acetyl-CoA
Correct Answer: Acetyl-CoA
Q7. How many ATP (or ATP equivalents) are consumed to produce one molecule of glucose from two pyruvate molecules in gluconeogenesis? (approximate)
- 2 ATP
- 4 ATP
- 6 ATP equivalents
- 10 ATP equivalents
Correct Answer: 6 ATP equivalents
Q8. Which hormone stimulates gluconeogenesis during fasting?
- Insulin
- Glucagon
- Gastrin
- Somatostatin
Correct Answer: Glucagon
Q9. Fructose 2,6-bisphosphate regulates glycolysis and gluconeogenesis by which mechanism?
- Activates FBPase-1 and inhibits PFK-1
- Inhibits both PFK-1 and FBPase-1
- Activates PFK-1 and inhibits FBPase-1
- Has no effect on PFK-1 or FBPase-1
Correct Answer: Activates PFK-1 and inhibits FBPase-1
Q10. Which enzyme catalyzes the final step of gluconeogenesis, converting glucose-6-phosphate to glucose?
- Glucose-6-phosphatase
- Hexokinase
- Glucose isomerase
- Phosphoglucose mutase
Correct Answer: Glucose-6-phosphatase
Q11. Gluconeogenesis occurs in which cellular compartments?
- Only cytosol
- Mitochondria and cytosol
- Only mitochondria
- Endoplasmic reticulum only
Correct Answer: Mitochondria and cytosol
Q12. Which coenzyme provides reducing equivalents for the glyceraldehyde-3-phosphate dehydrogenase step reversal in gluconeogenesis?
- NADP+
- NADH
- FADH2
- ATP
Correct Answer: NADH
Q13. The Cori cycle connects which two tissues for recycling lactate into glucose?
- Liver and adipose tissue
- Muscle and liver
- Brain and kidney
- Pancreas and muscle
Correct Answer: Muscle and liver
Q14. Which amino acid is a major gluconeogenic precursor via transamination to pyruvate?
- Glutamate
- Alanine
- Lysine
- Leucine
Correct Answer: Alanine
Q15. Which condition increases gluconeogenesis by elevating glucagon and cortisol levels?
- Refed state after carbohydrate meal
- Fasting and stress
- High insulin infusion
- Lactation only
Correct Answer: Fasting and stress
Q16. Metformin reduces hepatic gluconeogenesis primarily by which mechanism?
- Directly activating PEPCK
- Inhibiting mitochondrial respiratory chain complex I and activating AMPK
- Increasing glucagon secretion
- Stimulating fructose-1,6-bisphosphatase
Correct Answer: Inhibiting mitochondrial respiratory chain complex I and activating AMPK
Q17. Which enzyme converts oxaloacetate to malate to shuttle reducing equivalents between mitochondria and cytosol?
- Malate dehydrogenase
- Malic enzyme
- Citrate synthase
- Aconitase
Correct Answer: Malate dehydrogenase
Q18. Deficiency of glucose-6-phosphatase causes which glycogen storage disease associated with impaired gluconeogenesis?
- Von Gierke disease (Type I)
- McArdle disease (Type V)
- Pompe disease (Type II)
- Hers disease (Type VI)
Correct Answer: Von Gierke disease (Type I)
Q19. Which enzyme is transcriptionally induced by glucagon to enhance gluconeogenesis?
- Hexokinase
- PEPCK
- Pyruvate dehydrogenase
- Pyruvate kinase
Correct Answer: PEPCK
Q20. Glycerol contributes to gluconeogenesis after phosphorylation by which enzyme?
- Glycerol kinase
- Glycerol-3-phosphate dehydrogenase
- Glycerol phosphate acyltransferase
- Lipase
Correct Answer: Glycerol kinase
Q21. Which of the following best describes the role of acetyl-CoA in gluconeogenesis regulation?
- Acetyl-CoA inhibits pyruvate carboxylase
- Acetyl-CoA activates pyruvate carboxylase and signals increased gluconeogenesis
- Acetyl-CoA is a direct substrate for gluconeogenesis
- Acetyl-CoA decreases expression of PEPCK
Correct Answer: Acetyl-CoA activates pyruvate carboxylase and signals increased gluconeogenesis
Q22. Which bypass reaction in gluconeogenesis occurs in the endoplasmic reticulum?
- Conversion of pyruvate to oxaloacetate
- Fructose-1,6-bisphosphate to fructose-6-phosphate
- Glucose-6-phosphate to glucose
- PEP to 2-phosphoglycerate
Correct Answer: Glucose-6-phosphate to glucose
Q23. Which of the following inhibits gluconeogenesis by increasing fructose 2,6-bisphosphate levels?
- Glucagon signaling
- Insulin signaling
- High cortisol levels
- Starvation hormones
Correct Answer: Insulin signaling
Q24. PEPCK exists in which cellular isoforms relevant to gluconeogenesis?
- Only cytosolic PEPCK
- Cytosolic and mitochondrial PEPCK isoforms
- Only mitochondrial PEPCK
- Only nuclear PEPCK
Correct Answer: Cytosolic and mitochondrial PEPCK isoforms
Q25. During prolonged fasting, which organ increasingly contributes to gluconeogenesis along with the liver?
- Heart
- Kidney cortex
- Lung
- Skin
Correct Answer: Kidney cortex
Q26. What is the role of fructose-1,6-bisphosphatase in gluconeogenesis?
- Converts fructose-6-phosphate to fructose-1,6-bisphosphate
- Converts fructose-1,6-bisphosphate to fructose-6-phosphate
- Converts glucose to glucose-6-phosphate
- Converts pyruvate to acetyl-CoA
Correct Answer: Converts fructose-1,6-bisphosphate to fructose-6-phosphate
Q27. Which metabolite is a potent allosteric inhibitor of fructose-1,6-bisphosphatase?
- AMP
- Citrate
- ATP
- Acetyl-CoA
Correct Answer: AMP
Q28. In type 2 diabetes, hepatic gluconeogenesis is often:
- Decreased due to insulin hypersensitivity
- Increased contributing to fasting hyperglycemia
- Unaffected
- Completely suppressed by metformin in all patients
Correct Answer: Increased contributing to fasting hyperglycemia
Q29. Which enzyme provides cytosolic NADH by converting oxaloacetate to malate in the gluconeogenic shuttle?
- Malic enzyme
- Cytosolic malate dehydrogenase
- Mitochondrial malate dehydrogenase only
- Aconitase
Correct Answer: Cytosolic malate dehydrogenase
Q30. Which statement about lactate as a gluconeogenic substrate is correct?
- Lactate cannot be used for gluconeogenesis
- Lactate is converted directly to glucose in the cytosol
- Lactate inhibits PEPCK activity
Correct Answer: Lactate is converted to pyruvate by lactate dehydrogenase and then used for gluconeogenesis
Q31. The rate-controlling steps of gluconeogenesis are primarily regulated at which levels?
- Only by changes in substrate concentration
- Allosteric effectors, hormonal regulation, and gene expression
- Only by covalent modification of enzymes
- Only by compartmentalization
Correct Answer: Allosteric effectors, hormonal regulation, and gene expression
Q32. Which enzyme links amino acid catabolism to gluconeogenesis by converting amino acids into gluconeogenic intermediates?
- Alanine transaminase (ALT)
- Lipase
- Glycogen phosphorylase
- Acetyl-CoA carboxylase
Correct Answer: Alanine transaminase (ALT)
Q33. Which drug class can reduce hepatic gluconeogenesis and is commonly used in type 2 diabetes management?
- Sulfonylureas
- Biguanides (e.g., metformin)
- Beta-blockers
- Statins
Correct Answer: Biguanides (e.g., metformin)
Q34. Which metabolite accumulation signals high energy status and therefore inhibits gluconeogenesis?
- AMP
- ATP
- Fructose-2,6-bisphosphate
- cAMP
Correct Answer: ATP
Q35. Which enzyme interconverts dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, linking gluconeogenesis and glycolysis?
- Triose phosphate isomerase
- Glyceraldehyde-3-phosphate dehydrogenase
- Aldolase
- Enolase
Correct Answer: Triose phosphate isomerase
Q36. Which transcription factor family is involved in upregulating gluconeogenic genes during fasting?
- SREBP family
- Forkhead box O (FOXO) family
- P-parkinson family
- HIF family
Correct Answer: Forkhead box O (FOXO) family
Q37. During intense muscular activity, what happens to lactate production and its effect on hepatic gluconeogenesis?
- Lactate production decreases and gluconeogenesis shuts down
- Lactate production increases, supplying substrate for hepatic gluconeogenesis via the Cori cycle
- Lactate is stored in muscle as glycogen and not used by liver
- Lactate inhibits hepatic gluconeogenesis directly
Correct Answer: Lactate production increases, supplying substrate for hepatic gluconeogenesis via the Cori cycle
Q38. Which enzyme catalyzes the conversion of pyruvate to acetyl-CoA, thereby linking glycolysis to the TCA cycle and opposing gluconeogenesis?
- Pyruvate dehydrogenase complex (PDH)
- Pyruvate carboxylase
- PEPCK
- Pyruvate kinase
Correct Answer: Pyruvate dehydrogenase complex (PDH)
Q39. Which metabolite activates fructose-1,6-bisphosphatase and promotes gluconeogenesis?
- AMP
- Citrate
- Fructose-2,6-bisphosphate
- ADP
Correct Answer: Citrate
Q40. Which one of these statements about gluconeogenesis and glycolysis is TRUE?
- They are exact reverse pathways with identical enzymes.
- Gluconeogenesis uses unique bypass reactions to circumvent irreversible glycolytic steps.
- Gluconeogenesis occurs only in fed state.
- Gluconeogenesis consumes no ATP.
Correct Answer: Gluconeogenesis uses unique bypass reactions to circumvent irreversible glycolytic steps.
Q41. During starvation, which substrate becomes increasingly important for gluconeogenesis?
- Dietary glucose
- Glycerol from adipose tissue lipolysis
- Fructose from diet
- Ketone bodies as direct glucose precursors
Correct Answer: Glycerol from adipose tissue lipolysis
Q42. The mitochondrial enzyme that converts oxaloacetate to phosphoenolpyruvate in some tissues is:
- Mitochondrial PEPCK
- Mitochondrial hexokinase
- Citrate lyase
- Mitochondrial aldolase
Correct Answer: Mitochondrial PEPCK
Q43. Which of the following decreases cellular fructose 2,6-bisphosphate levels and thereby stimulates gluconeogenesis?
- Insulin activating PFK-2 kinase activity
- Glucagon activating PFK-2 phosphatase activity via PKA
- High glucose stimulating PFK-1
- Amino acids activating mTOR only
Correct Answer: Glucagon activating PFK-2 phosphatase activity via PKA
Q44. Which metabolic condition increases hepatic gluconeogenesis despite hyperglycemia in diabetes?
- Insulin resistance
- Complete absence of glucagon
- Excessive insulin sensitivity
- Hypoglycemia only
Correct Answer: Insulin resistance
Q45. Which enzyme converts glycerol-3-phosphate to dihydroxyacetone phosphate during gluconeogenesis from glycerol?
- Glycerol kinase
- Glycerol-3-phosphate dehydrogenase
- Triacylglycerol lipase
- Fructokinase
Correct Answer: Glycerol-3-phosphate dehydrogenase
Q46. Which molecule directly activates PEPCK transcription in response to fasting signals?
- Insulin receptor substrate
- cAMP-response element-binding protein (CREB) via cAMP-PKA pathway
- Glycogen synthase
- SGLT1 transporter
Correct Answer: cAMP-response element-binding protein (CREB) via cAMP-PKA pathway
Q47. Which statement best describes net carbon flow in gluconeogenesis from two molecules of lactate?
- Two lactate yield one glucose with net loss of carbon
- Two lactate (3C each) are converted to one glucose (6C) conserving carbon
- One lactate yields one glucose directly
- Lactate carbons are lost as CO2 during gluconeogenesis
Correct Answer: Two lactate (3C each) are converted to one glucose (6C) conserving carbon
Q48. Which enzyme deficiency would most directly impair the conversion of oxaloacetate to phosphoenolpyruvate?
- Pyruvate carboxylase deficiency
- PEP carboxykinase (PEPCK) deficiency
- Fructose-1,6-bisphosphatase deficiency
- Glucose-6-phosphatase deficiency
Correct Answer: PEP carboxykinase (PEPCK) deficiency
Q49. Which of the following metabolic signals favors gluconeogenesis over glycolysis in the liver?
- High insulin/low glucagon ratio
- High AMP and high fructose 2,6-bisphosphate
- High glucagon/cAMP and low fructose 2,6-bisphosphate
- Excess dietary carbohydrate immediately after a meal
Correct Answer: High glucagon/cAMP and low fructose 2,6-bisphosphate
Q50. From a pharmacology perspective, which therapeutic approach reduces excessive gluconeogenesis in type 2 diabetes?
- Drugs that increase hepatic gluconeogenic gene expression
- Agents that enhance hepatic insulin signaling or activate AMPK (e.g., metformin)
- Beta-agonists that raise cAMP in liver
- Glucagon receptor agonists
Correct Answer: Agents that enhance hepatic insulin signaling or activate AMPK (e.g., metformin)
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