Gluconeogenesis is a vital metabolic pathway that synthesizes glucose from non-carbohydrate precursors, crucial for maintaining blood glucose during fasting and stress. This Student-friendly guide focuses on the significance of gluconeogenesis for B. Pharm students, highlighting key enzymes, regulation, tissue specificity, energy cost, and clinical implications in diabetes and hypoglycemia. Understanding gluconeogenesis is essential for pharmacology, therapeutics, and biochemical exam preparation. These well-crafted MCQs emphasize mechanism, hormonal control, drug interactions, and biochemical regulation, helping students deepen conceptual knowledge and improve test performance. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which enzyme catalyzes the irreversibly committed step of gluconeogenesis that converts pyruvate to oxaloacetate?
- Pyruvate kinase
- Pyruvate carboxylase
- Phosphoenolpyruvate carboxykinase (PEPCK)
- Fructose-1,6-bisphosphatase
Correct Answer: Pyruvate carboxylase
Q2. In which organ is gluconeogenesis most active during prolonged fasting?
- Brain
- Adipose tissue
- Liver
- Skeletal muscle
Correct Answer: Liver
Q3. Which cofactor is essential for the activity of pyruvate carboxylase?
- Thiamine pyrophosphate (TPP)
- Biotin
- FAD
- NAD+
Correct Answer: Biotin
Q4. How many high-energy phosphate bonds (ATP or GTP equivalents) are consumed in the net synthesis of one molecule of glucose from two molecules of pyruvate?
- 2
- 4
- 6
- 8
Correct Answer: 6
Q5. Which enzyme provides the final step of gluconeogenesis by converting glucose-6-phosphate to free glucose?
- Glucokinase
- Hexokinase
- Glucose-6-phosphatase
- Phosphoglucomutase
Correct Answer: Glucose-6-phosphatase
Q6. Why can skeletal muscle not contribute to blood glucose via gluconeogenesis?
- It lacks PEPCK
- It cannot export glucose because it lacks glucose-6-phosphatase
- It lacks pyruvate carboxylase
- It has no substrates for gluconeogenesis
Correct Answer: It cannot export glucose because it lacks glucose-6-phosphatase
Q7. Which substrate is NOT a major precursor for gluconeogenesis?
- Lactate
- Glycerol
- Acetyl-CoA
- Alanine
Correct Answer: Acetyl-CoA
Q8. Which enzyme bypasses the irreversible phosphofructokinase-1 (PFK-1) step in gluconeogenesis?
- Fructose-1,6-bisphosphatase
- Fructokinase
- Aldolase
- Enolase
Correct Answer: Fructose-1,6-bisphosphatase
Q9. Which hormone stimulates gluconeogenesis during fasting?
- Insulin
- Glucagon
- Cholecystokinin
- Leptin
Correct Answer: Glucagon
Q10. Fructose-2,6-bisphosphate has what effect on gluconeogenesis?
- Activates fructose-1,6-bisphosphatase and stimulates gluconeogenesis
- Inhibits PFK-1 and stimulates gluconeogenesis
- Inhibits fructose-1,6-bisphosphatase and inhibits gluconeogenesis
- Activates PFK-1 and inhibits gluconeogenesis
Correct Answer: Activates PFK-1 and inhibits gluconeogenesis
Q11. Which substrate must be converted to dihydroxyacetone phosphate (DHAP) before entering gluconeogenesis from triglyceride breakdown?
- Glycerol
- Acetoacetate
- Palmitate
- Lactate
Correct Answer: Glycerol
Q12. Which enzyme converts oxaloacetate to phosphoenolpyruvate (PEP) in gluconeogenesis?
- PEP carboxykinase (PEPCK)
- Pyruvate dehydrogenase
- Malate dehydrogenase
- Pyruvate carboxylase
Correct Answer: PEP carboxykinase (PEPCK)
Q13. Where is glucose-6-phosphatase located within the cell?
- Mitochondrial matrix
- Cytosol
- Endoplasmic reticulum membrane/lumen
- Golgi apparatus
Correct Answer: Endoplasmic reticulum membrane/lumen
Q14. Which transcriptional coactivator upregulates gluconeogenic gene expression in the liver?
- PGC-1α
- SREBP-1c
- HIF-1α
- mTORC1
Correct Answer: PGC-1α
Q15. Acetyl-CoA acts as an allosteric regulator of which gluconeogenic enzyme?
- Fructose-1,6-bisphosphatase
- Pyruvate kinase
- Pyruvate carboxylase
- Glucose-6-phosphatase
Correct Answer: Pyruvate carboxylase
Q16. Which pathway describes conversion of muscle-derived lactate to glucose in the liver?
- Cori cycle
- Urea cycle
- Krebs cycle
- Pentose phosphate pathway
Correct Answer: Cori cycle
Q17. Which enzyme’s deficiency leads to inability to perform gluconeogenesis and severe fasting hypoglycemia due to absence of fructose-1,6-bisphosphatase?
- G6PD deficiency
- Fructose-1,6-bisphosphatase deficiency
- Pyruvate kinase deficiency
- Glucokinase deficiency
Correct Answer: Fructose-1,6-bisphosphatase deficiency
Q18. Which molecule provides the reducing equivalents (NADH) for cytosolic steps of gluconeogenesis when oxaloacetate is transported as malate?
- Citrate
- Malate shuttle
- Glycerol-3-phosphate shuttle
- Urea
Correct Answer: Malate shuttle
Q19. Which enzyme is transcriptionally downregulated by insulin, reducing gluconeogenesis?
- PEPCK
- Hexokinase
- Glycogen phosphorylase
- G6PD
Correct Answer: PEPCK
Q20. Metformin lowers hepatic glucose production primarily by which mechanism related to gluconeogenesis?
- Activating pyruvate carboxylase directly
- Inhibiting mitochondrial respiratory chain complex I and activating AMPK to suppress gluconeogenic gene expression
- Increasing fructose-2,6-bisphosphate synthesis
- Activating PEPCK expression
Correct Answer: Inhibiting mitochondrial respiratory chain complex I and activating AMPK to suppress gluconeogenic gene expression
Q21. Which amino acid is the principal gluconeogenic amino acid that donates carbon via alanine transaminase?
- Leucine
- Lysine
- Alanine
- Isoleucine
Correct Answer: Alanine
Q22. How many irreversible bypass reactions are present in gluconeogenesis compared to glycolysis?
- One
- Two
- Three
- Four
Correct Answer: Three
Q23. Which of the following inhibits fructose-1,6-bisphosphatase and thereby decreases gluconeogenesis?
- AMP
- Citrate
- ATP
- Acetyl-CoA
Correct Answer: AMP
Q24. Which enzyme interconverts fructose-6-phosphate and glucose-6-phosphate during gluconeogenesis?
- Phosphoglucose isomerase
- Hexokinase
- Glucose-6-phosphatase
- Phosphofructokinase-2
Correct Answer: Phosphoglucose isomerase
Q25. What is the role of glycerol kinase in hepatic gluconeogenesis?
- Converts glycerol to glycerol-3-phosphate which enters glycolysis/gluconeogenesis
- Converts glycerol to glyceraldehyde directly
- Breaks down triglycerides to free glycerol and fatty acids
- Converts glycerol to pyruvate
Correct Answer: Converts glycerol to glycerol-3-phosphate which enters glycolysis/gluconeogenesis
Q26. Which nucleotide is consumed by cytosolic PEP carboxykinase when converting oxaloacetate to PEP in some tissues?
- ATP
- GTP
- CTP
- UTP
Correct Answer: GTP
Q27. During prolonged fasting, which organ increases its gluconeogenic activity to help maintain blood glucose besides the liver?
- Brain
- Kidney cortex
- Adipose tissue
- Skeletal muscle
Correct Answer: Kidney cortex
Q28. Which reaction in gluconeogenesis requires transport of intermediates between mitochondria and cytosol?
- Fructose-1,6-bisphosphate to fructose-6-phosphate
- Oxaloacetate to phosphoenolpyruvate conversion involving malate or aspartate shuttles
- Glucose-6-phosphate hydrolysis
- Glycerol phosphorylation
Correct Answer: Oxaloacetate to phosphoenolpyruvate conversion involving malate or aspartate shuttles
Q29. Which enzyme of gluconeogenesis is inhibited by phosphorylation via insulin signaling indirectly?
- PEPCK via decreased transcription
- Glucose-6-phosphatase by direct phosphorylation
- Fructose-1,6-bisphosphatase by phosphorylation
- Pyruvate carboxylase by phosphorylation
Correct Answer: PEPCK via decreased transcription
Q30. Which metabolite signals a high-energy state and inhibits gluconeogenesis?
- AMP
- ADP
- ATP
- Pi
Correct Answer: ATP
Q31. Which enzyme catalyzes the conversion of lactate to pyruvate, providing substrate for gluconeogenesis?
- Lactate dehydrogenase
- Alanine transaminase
- Malate dehydrogenase
- Pyruvate kinase
Correct Answer: Lactate dehydrogenase
Q32. Which clinical condition is characterized by excessive gluconeogenesis contributing to hyperglycemia?
- Type 1 diabetes mellitus
- Type 2 diabetes mellitus
- Hypothyroidism
- Phenylketonuria
Correct Answer: Type 2 diabetes mellitus
Q33. Why is acetyl-CoA from fatty acid oxidation not a gluconeogenic substrate?
- It cannot be converted to oxaloacetate; it is fully oxidized to CO2 via TCA cycle
- It is impermeable to mitochondrial membrane
- It lacks phosphate groups
- It inhibits gluconeogenic enzymes directly
Correct Answer: It cannot be converted to oxaloacetate; it is fully oxidized to CO2 via TCA cycle
Q34. Which enzyme catalyzes the hydrolysis of fructose-2,6-bisphosphate, thereby relieving inhibition of gluconeogenesis?
- PFK-1
- PFK-2/FBPase-2 bifunctional enzyme (FBPase-2 activity)
- Fructokinase
- Fructose-1,6-bisphosphatase
Correct Answer: PFK-2/FBPase-2 bifunctional enzyme (FBPase-2 activity)
Q35. Which drug class indirectly reduces hepatic gluconeogenesis by improving insulin sensitivity?
- Sulfonylureas
- Thiazolidinediones (TZDs)
- Alpha-glucosidase inhibitors
- Insulin secretagogues
Correct Answer: Thiazolidinediones (TZDs)
Q36. Which vitamin deficiency impairs pyruvate carboxylase function leading to reduced gluconeogenesis?
- Vitamin B1 (thiamine)
- Vitamin B7 (biotin)
- Vitamin B2 (riboflavin)
- Vitamin B3 (niacin)
Correct Answer: Vitamin B7 (biotin)
Q37. During acute exercise, which process increases lactate production that can later be used for gluconeogenesis?
- Increased aerobic respiration
- Increased anaerobic glycolysis
- Increased gluconeogenesis
- Increased β-oxidation
Correct Answer: Increased anaerobic glycolysis
Q38. Which of the following is a key regulatory enzyme inhibited by AMP during low-energy states, thereby preventing gluconeogenesis?
- Fructose-1,6-bisphosphatase
- Pyruvate carboxylase
- PEP carboxykinase
- Glucose-6-phosphatase
Correct Answer: Fructose-1,6-bisphosphatase
Q39. Which pathway links amino acid catabolism to gluconeogenesis by providing oxaloacetate or pyruvate?
- Urea cycle
- Transamination reactions
- Fatty acid synthesis
- Ketogenesis
Correct Answer: Transamination reactions
Q40. PEPCK exists in cytosolic and mitochondrial isoforms; which factor determines their relative contribution to gluconeogenesis?
- Hormonal environment only
- Substrate availability, tissue type and species-specific expression
- Blood pH exclusively
- Presence of insulin receptor only
Correct Answer: Substrate availability, tissue type and species-specific expression
Q41. Which metabolite accumulation in diabetes stimulates gluconeogenesis and worsens hyperglycemia?
- Fructose-2,6-bisphosphate
- Acetyl-CoA
- Alanine and glycerol from increased proteolysis and lipolysis
- Glycogen
Correct Answer: Alanine and glycerol from increased proteolysis and lipolysis
Q42. Which enzyme is directly responsible for converting pyruvate to PEP via a two-step mitochondrial and cytosolic process?
- Pyruvate dehydrogenase alone
- Pyruvate carboxylase and PEP carboxykinase (PEPCK)
- Pyruvate kinase and enolase
- Lactate dehydrogenase and malate dehydrogenase
Correct Answer: Pyruvate carboxylase and PEP carboxykinase (PEPCK)
Q43. Which of the following is a pharmacological strategy to reduce excessive gluconeogenesis in type 2 diabetes?
- Stimulating PEPCK gene expression
- Activating fructose-1,6-bisphosphatase
- Activating AMPK to suppress gluconeogenic gene expression
- Increasing hepatic glucagon signaling
Correct Answer: Activating AMPK to suppress gluconeogenic gene expression
Q44. Which intermediate links glycolysis and gluconeogenesis and can be converted in either direction depending on cell energy status?
- Pyruvate
- Fructose-2,6-bisphosphate
- Glucose-6-phosphate
- Phosphoenolpyruvate (PEP)
Correct Answer: Glucose-6-phosphate
Q45. Which experimental observation would indicate increased gluconeogenesis in the liver?
- Decreased expression of PEPCK and G6Pase mRNA
- Increased hepatic lactate uptake and increased glucose release
- Increased muscle glycogen synthesis
- Decreased blood glucose levels during fasting
Correct Answer: Increased hepatic lactate uptake and increased glucose release
Q46. What is the effect of cortisol on hepatic gluconeogenesis?
- Suppresses transcription of gluconeogenic enzymes
- Enhances transcription of gluconeogenic enzymes and increases substrate availability
- Directly inhibits pyruvate carboxylase activity
- Has no effect on gluconeogenesis
Correct Answer: Enhances transcription of gluconeogenic enzymes and increases substrate availability
Q47. Which metabolic cycle provides nitrogen disposal while linking to gluconeogenic amino acid metabolism?
- Citric acid cycle
- Urea cycle
- Glyoxylate cycle
- Pentose phosphate pathway
Correct Answer: Urea cycle
Q48. Increased activity of which enzyme would most directly lower gluconeogenic flux by increasing glycolytic flux?
- Glucose-6-phosphatase
- Phosphofructokinase-1 (PFK-1)
- PEP carboxykinase
- Pyruvate carboxylase
Correct Answer: Phosphofructokinase-1 (PFK-1)
Q49. Inherited deficiency of glucose-6-phosphatase causes which disease characterized by impaired gluconeogenesis and glycogenolysis?
- Von Gierke disease (Glycogen storage disease type I)
- McArdle disease
- Pompe disease
- Anderson disease
Correct Answer: Von Gierke disease (Glycogen storage disease type I)
Q50. Which laboratory finding is most consistent with increased hepatic gluconeogenesis?
- Low blood glucose and low plasma alanine
- High fasting blood glucose with elevated hepatic PEPCK expression
- Decreased blood lactate utilization by liver
- Low glucagon levels
Correct Answer: High fasting blood glucose with elevated hepatic PEPCK expression
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