Formation of ketone bodies MCQs With Answer is a focused study resource designed for B. Pharm students to master ketogenesis, regulation, clinical implications, and biochemical pathways. This introduction covers ketone body synthesis in liver mitochondria, key enzymes like mitochondrial HMG‑CoA synthase and HMG‑CoA lyase, major products (acetoacetate, β‑hydroxybutyrate, acetone), hormonal control by insulin and glucagon, and the metabolic context of fasting, diabetes, and alcohol. Emphasis on mechanisms, enzyme regulation, NADH/NAD+ effects, and diagnostic tests will help pharmacy students understand therapeutic and clinical relevance. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Where are ketone bodies primarily synthesized?
- Liver mitochondria
- Adipose tissue cytosol
- Pancreatic beta cells
- Skeletal muscle sarcoplasm
Correct Answer: Liver mitochondria
Q2. Which enzyme is considered the rate-limiting enzyme of ketogenesis?
- Mitochondrial HMG‑CoA synthase
- HMG‑CoA reductase
- Acetoacetyl‑CoA thiolase
- Succinyl‑CoA:3‑ketoacid CoA transferase (thiophorase)
Correct Answer: Mitochondrial HMG‑CoA synthase
Q3. HMG‑CoA lyase catalyzes the formation of which primary ketone body?
- Acetoacetate
- Glucose
- Malonyl‑CoA
- Citrate
Correct Answer: Acetoacetate
Q4. Which of the following are the major ketone bodies produced in the liver?
- Acetoacetate, β‑hydroxybutyrate, and acetone
- Acetyl‑CoA, malonyl‑CoA, and citrate
- Pyruvate, lactate, and alanine
- Cholesterol, bile acids, and triglycerides
Correct Answer: Acetoacetate, β‑hydroxybutyrate, and acetone
Q5. Which enzyme reduces acetoacetate to β‑hydroxybutyrate?
- β‑Hydroxybutyrate dehydrogenase
- Acetyl‑CoA carboxylase
- HMG‑CoA reductase
- Pyruvate dehydrogenase
Correct Answer: β‑Hydroxybutyrate dehydrogenase
Q6. An increased NADH/NAD+ ratio in the liver will shift ketone production toward which compound?
- β‑Hydroxybutyrate
- Acetoacetate
- Acetone
- Oxaloacetate
Correct Answer: β‑Hydroxybutyrate
Q7. Which tissue can adapt to use ketone bodies as a major fuel during prolonged fasting?
- Brain
- Red blood cells
- Adipose tissue (for release)
- Hepatocytes (for oxidation)
Correct Answer: Brain
Q8. Which enzyme required for ketone utilization is absent in liver, preventing hepatic oxidation of ketone bodies?
- Succinyl‑CoA:3‑ketoacid CoA transferase (thiophorase)
- β‑Hydroxybutyrate dehydrogenase
- Acetoacetyl‑CoA thiolase
- HMG‑CoA lyase
Correct Answer: Succinyl‑CoA:3‑ketoacid CoA transferase (thiophorase)
Q9. The nitroprusside reagent (acetest) detects which ketone bodies in urine?
- Acetoacetate and acetone
- β‑Hydroxybutyrate only
- All three: acetoacetate, β‑hydroxybutyrate, and acetone
- None of the ketone bodies
Correct Answer: Acetoacetate and acetone
Q10. Which hormonal change most strongly promotes hepatic ketogenesis?
- Low insulin and high glucagon
- High insulin and low glucagon
- Elevated thyroid hormone only
- High growth hormone alone
Correct Answer: Low insulin and high glucagon
Q11. The carbon source for ketone body synthesis is primarily:
- Acetyl‑CoA derived from fatty acid β‑oxidation and ketogenic amino acids
- Glucose from glycolysis
- Oxaloacetate from the TCA cycle
- Fructose from the liver
Correct Answer: Acetyl‑CoA derived from fatty acid β‑oxidation and ketogenic amino acids
Q12. Uncontrolled type 1 diabetes leads to increased ketogenesis because of:
- Absolute insulin deficiency and increased lipolysis
- Excessive insulin action
- Increased glycogen synthesis
- Decreased glucagon secretion
Correct Answer: Absolute insulin deficiency and increased lipolysis
Q13. Acetone is formed from acetoacetate by which process?
- Spontaneous decarboxylation (non‑enzymatic)
- HMG‑CoA synthase action
- Succinyl‑CoA transferase reaction
- β‑Oxidation in mitochondria
Correct Answer: Spontaneous decarboxylation (non‑enzymatic)
Q14. Clinical ketosis refers to which of the following?
- Elevated levels of ketone bodies in blood and urine
- Low blood glucose with normal ketone levels
- Increased glycogen storage
- Excess insulin causing hypoglycemia
Correct Answer: Elevated levels of ketone bodies in blood and urine
Q15. Which hormone directly inhibits ketogenesis?
- Insulin
- Glucagon
- Epinephrine
- Cortisol
Correct Answer: Insulin
Q16. Which amino acids are exclusively ketogenic?
- Leucine and lysine
- Alanine and glycine
- Glutamine and asparagine
- Serine and cysteine
Correct Answer: Leucine and lysine
Q17. The enzyme that condenses two acetyl‑CoA molecules to form acetoacetyl‑CoA is:
- Acetoacetyl‑CoA thiolase (thiolase)
- HMG‑CoA lyase
- Pyruvate carboxylase
- Malate dehydrogenase
Correct Answer: Acetoacetyl‑CoA thiolase (thiolase)
Q18. Oxaloacetate depletion favors ketogenesis because:
- Acetyl‑CoA cannot enter the TCA cycle and is diverted to ketone synthesis
- It directly activates HMG‑CoA lyase
- It increases glycolysis
- It enhances glycogen synthesis
Correct Answer: Acetyl‑CoA cannot enter the TCA cycle and is diverted to ketone synthesis
Q19. The primary metabolic source of acetyl‑CoA for ketogenesis is:
- Fatty acid β‑oxidation
- Glycogenolysis
- Pentose phosphate pathway
- Gluconeogenesis from lactate
Correct Answer: Fatty acid β‑oxidation
Q20. Alcoholic ketoacidosis often shows a high β‑hydroxybutyrate to acetoacetate ratio because alcohol metabolism:
- Increases the hepatic NADH/NAD+ ratio
- Decreases NADH production
- Inhibits alcohol dehydrogenase
- Increases insulin secretion
Correct Answer: Increases the hepatic NADH/NAD+ ratio
Q21. For accurate clinical measurement of ketone burden in diabetic ketoacidosis, which analyte is preferred?
- Blood β‑hydroxybutyrate concentration
- Urine nitroprusside test only
- Breath acetone level only
- Blood acetoacetate concentration only
Correct Answer: Blood β‑hydroxybutyrate concentration
Q22. Which organ is unable to utilize ketone bodies for energy due to lack of thiophorase?
- Liver
- Heart
- Skeletal muscle
- Kidney cortex
Correct Answer: Liver
Q23. After the onset of prolonged fasting, approximately how many days until the brain significantly uses ketone bodies?
- About 3 days
- Immediately within hours
- After 2 weeks only
- Never; brain cannot use ketones
Correct Answer: About 3 days
Q24. How are ketone bodies transported in the blood?
- They are water‑soluble and circulate dissolved in plasma
- They are bound tightly to albumin
- They are transported within lipoprotein particles
- They require specific carrier proteins like hemoglobin
Correct Answer: They are water‑soluble and circulate dissolved in plasma
Q25. Ketone bodies cross the blood–brain barrier primarily via:
- Monocarboxylate transporters (MCTs)
- Glucose transporters (GLUTs)
- Fatty acid transport proteins
- Endocytosis only
Correct Answer: Monocarboxylate transporters (MCTs)
Q26. There are isoforms of HMG‑CoA synthase. Which isoform is involved in ketogenesis?
- Mitochondrial HMG‑CoA synthase (HMGCS2)
- Cytosolic HMG‑CoA synthase for cholesterol synthesis
- Peroxisomal HMG‑CoA synthase
- Endoplasmic reticulum HMG‑CoA synthase
Correct Answer: Mitochondrial HMG‑CoA synthase (HMGCS2)
Q27. The cofactor used by β‑hydroxybutyrate dehydrogenase for the reversible reaction is:
- NAD+/NADH
- FAD/FADH2
- Biotin
- PLP (pyridoxal phosphate)
Correct Answer: NAD+/NADH
Q28. Acetone is clinically significant because it is:
- Volatile and gives a fruity odor on the breath
- Used as the main energy substrate for the brain
- Detected by nitroprusside test only
- A high‑energy metabolite converted to ATP
Correct Answer: Volatile and gives a fruity odor on the breath
Q29. During diabetic ketoacidosis (DKA), which ketone is usually predominant?
- β‑Hydroxybutyrate
- Acetoacetate
- Acetone
- Acetyl‑CoA
Correct Answer: β‑Hydroxybutyrate
Q30. Which of the following laboratory tests can underestimate total ketone burden in DKA?
- Nitroprusside urine test
- Blood β‑hydroxybutyrate assay
- Arterial blood gas for pH
- Serum electrolyte panel
Correct Answer: Nitroprusside urine test
Q31. Which amino acid is both glucogenic and ketogenic?
- Isoleucine
- Leucine (only ketogenic)
- Lysine (only ketogenic)
- Alanine (only glucogenic)
Correct Answer: Isoleucine
Q32. In peripheral tissues, which enzyme converts acetoacetate to acetoacetyl‑CoA for oxidation?
- Succinyl‑CoA:3‑ketoacid CoA transferase (thiophorase)
- HMG‑CoA lyase
- HMG‑CoA synthase
- Acetoacetate decarboxylase
Correct Answer: Succinyl‑CoA:3‑ketoacid CoA transferase (thiophorase)
Q33. Ketogenesis is increased in which nutritional state?
- Prolonged fasting
- Fed state after carbohydrate meal
- High‑insulin infusion
- Postprandial lipogenesis
Correct Answer: Prolonged fasting
Q34. Which statement about hepatic ketone metabolism is true?
- Liver produces ketone bodies but does not oxidize them due to lack of thiophorase
- Liver both produces and extensively oxidizes ketone bodies
- Liver cannot produce ketone bodies at all
- Liver converts ketones back to glucose directly
Correct Answer: Liver produces ketone bodies but does not oxidize them due to lack of thiophorase
Q35. A primary carnitine deficiency would have what effect on ketone body formation?
- Decrease ketone body production due to impaired fatty acid entry into mitochondria
- Increase ketone production due to excess fatty acid oxidation
- No effect on ketogenesis
- Convert ketogenesis to cholesterol synthesis
Correct Answer: Decrease ketone body production due to impaired fatty acid entry into mitochondria
Q36. Inhibition of carnitine palmitoyltransferase I (CPT I) would cause:
- Reduced hepatic ketogenesis
- Increased ketone body production
- No change in fatty acid oxidation
- Enhanced transport of fatty acids into mitochondria
Correct Answer: Reduced hepatic ketogenesis
Q37. HMG‑CoA lyase is localized in which cellular compartment?
- Mitochondrial matrix
- Endoplasmic reticulum lumen
- Cytosol
- Peroxisome
Correct Answer: Mitochondrial matrix
Q38. Which metabolic change favors conversion of acetoacetate to β‑hydroxybutyrate?
- High mitochondrial NADH
- High mitochondrial NAD+
- Low acetyl‑CoA levels
- High oxaloacetate concentration
Correct Answer: High mitochondrial NADH
Q39. Why can the nitroprusside test lead to false reassurance in severe DKA?
- It does not detect β‑hydroxybutyrate, which may predominate
- It is overly sensitive to β‑hydroxybutyrate
- It measures blood glucose instead of ketones
- It detects only cholesterol derivatives
Correct Answer: It does not detect β‑hydroxybutyrate, which may predominate
Q40. Accumulation of ketone bodies can lead to metabolic acidosis because:
- They are acidic and release protons in blood
- They raise blood bicarbonate levels
- They directly increase insulin secretion
- They convert to ammonia
Correct Answer: They are acidic and release protons in blood
Q41. Which of the following is NOT a ketone body?
- Acetyl‑CoA
- Acetoacetate
- β‑Hydroxybutyrate
- Acetone
Correct Answer: Acetyl‑CoA
Q42. Insulin reduces ketogenesis primarily by:
- Decreasing lipolysis and fatty acid supply to the liver
- Activating HMG‑CoA synthase
- Increasing hepatic fatty acid oxidation
- Stimulating glucagon release
Correct Answer: Decreasing lipolysis and fatty acid supply to the liver
Q43. A therapeutic ketogenic diet increases ketone production and is used clinically for which condition?
- Refractory epilepsy
- Acute bacterial infections
- Hyperinsulinemic hypoglycemia
- Acute pancreatitis
Correct Answer: Refractory epilepsy
Q44. Which cofactor provides the CoA necessary for conversion of acetoacetate into acetoacetyl‑CoA in peripheral tissues?
- Succinyl‑CoA donates CoA via thiophorase
- Free coenzyme Q10 directly supplies CoA
- Biotin supplies the CoA group
- PLP transfers CoA
Correct Answer: Succinyl‑CoA donates CoA via thiophorase
Q45. What initiates increased hepatic ketone synthesis during fasting?
- Enhanced mobilization and β‑oxidation of fatty acids
- Immediate rise in blood glucose
- Decreased glucagon secretion
- Increased dietary carbohydrate intake
Correct Answer: Enhanced mobilization and β‑oxidation of fatty acids
Q46. How does mitochondrial HMG‑CoA synthase differ functionally from the cytosolic HMG‑CoA pathway?
- Mitochondrial HMG‑CoA synthase participates in ketone synthesis, cytosolic pathway supplies cholesterol precursors
- Both isoforms produce ketone bodies equally
- Cytosolic HMG‑CoA synthase makes acetoacetate for ketogenesis
- Only cytosolic HMG‑CoA synthase is regulated by fasting
Correct Answer: Mitochondrial HMG‑CoA synthase participates in ketone synthesis, cytosolic pathway supplies cholesterol precursors
Q47. Which statement about acetone is correct?
- It is a volatile byproduct that is mostly exhaled or excreted and not used for major ATP production
- It is the primary ATP‑yielding ketone in muscle
- It is directly converted to glucose in the liver
- It is detected preferentially by the nitroprusside test
Correct Answer: It is a volatile byproduct that is mostly exhaled or excreted and not used for major ATP production
Q48. Why does the liver produce ketone bodies but not use them for its own energy?
- The liver lacks the thiophorase enzyme required for ketone utilization
- The liver has a special transporter that excludes ketones
- The liver converts all ketones immediately to cholesterol
- The liver uses only glucose as an energy source
Correct Answer: The liver lacks the thiophorase enzyme required for ketone utilization
Q49. Oxidation of odd‑chain fatty acids leads predominantly to products that:
- Enter gluconeogenesis (propionyl‑CoA → succinyl‑CoA)
- Directly form acetoacetate only
- Produce large amounts of acetone
- Are converted into cholesterol exclusively
Correct Answer: Enter gluconeogenesis (propionyl‑CoA → succinyl‑CoA)
Q50. For emergency monitoring of ketoacidosis in a hospital, which measurement is most reliable to track treatment response?
- Serial blood β‑hydroxybutyrate levels
- Single urine nitroprusside test at admission only
- Fasting blood glucose alone
- Breath acetone qualitative smell only
Correct Answer: Serial blood β‑hydroxybutyrate levels

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