Introduction: Understanding the utilization of ketone bodies is essential for B. Pharm students preparing for pharmacology, biochemistry, and clinical pharmacy exams. This concise guide explores ketogenesis, ketolysis, key enzymes (HMG-CoA synthase, HMG-CoA lyase, SCOT), major ketone bodies (acetoacetate, β-hydroxybutyrate, acetone), regulation by insulin and glucagon, transport via monocarboxylate transporters, and clinical relevance in diabetic ketoacidosis, starvation, and alcohol-induced ketoacidosis. Emphasis on metabolic pathways, laboratory detection (blood β‑hydroxybutyrate, nitroprusside test limitations), and therapeutic implications (nutritional ketosis, SGLT2 inhibitor–associated euglycemic DKA) will sharpen your conceptual and applied knowledge. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which of the following is the primary ketone body produced in the liver during prolonged fasting?
- Acetone
- Acetoacetate
- β‑Hydroxybutyrate
- Acetyl‑carnitine
Correct Answer: β‑Hydroxybutyrate
Q2. Where does ketogenesis primarily occur within hepatocytes?
- Cytosol
- Mitochondrial matrix
- Endoplasmic reticulum
- Peroxisome
Correct Answer: Mitochondrial matrix
Q3. Which enzyme catalyzes the rate‑limiting step of ketone body synthesis?
- HMG‑CoA synthase (mitochondrial)
- HMG‑CoA reductase
- Succinyl‑CoA:3‑ketoacid CoA transferase (SCOT)
- 3‑hydroxybutyrate dehydrogenase
Correct Answer: HMG‑CoA synthase (mitochondrial)
Q4. Why can the liver synthesize but not utilize ketone bodies for energy?
- Liver lacks mitochondrial HMG‑CoA synthase
- Liver lacks succinyl‑CoA:3‑ketoacid CoA transferase (SCOT)
- Liver cannot generate acetyl‑CoA
- Liver mitochondria lack NAD+
Correct Answer: Liver lacks succinyl‑CoA:3‑ketoacid CoA transferase (SCOT)
Q5. Which ketone body is formed by spontaneous decarboxylation of acetoacetate?
- β‑Hydroxybutyrate
- Acetone
- Acetyl‑CoA
- Acetoacetyl‑CoA
Correct Answer: Acetone
Q6. Which cofactor determines the interconversion between acetoacetate and β‑hydroxybutyrate?
- NADP+/NADPH
- NAD+/NADH
- Coenzyme A
Correct Answer: NAD+/NADH
Q7. The nitroprusside urine test detects which ketone bodies?
- β‑Hydroxybutyrate only
- Acetoacetate and acetone (indirectly)
- All three: acetoacetate, β‑hydroxybutyrate, acetone
- Acetyl‑CoA
Correct Answer: Acetoacetate and acetone (indirectly)
Q8. Which transporter family facilitates ketone body uptake into extrahepatic tissues?
- GLUT family
- Monocarboxylate transporters (MCTs)
- ABC transporters
- Fatty acid translocase (CD36)
Correct Answer: Monocarboxylate transporters (MCTs)
Q9. Which condition is characterized by high anion gap metabolic acidosis and elevated ketone bodies with hyperglycemia?
- Starvation ketosis
- Diabetic ketoacidosis (DKA)
- Alcoholic ketoacidosis
- Lactic acidosis
Correct Answer: Diabetic ketoacidosis (DKA)
Q10. Which metabolic signal directly stimulates hepatic ketogenesis?
- High insulin to glucagon ratio
- Low fatty acid availability
- Elevated acetyl‑CoA and increased fatty acid oxidation
- High malonyl‑CoA levels
Correct Answer: Elevated acetyl‑CoA and increased fatty acid oxidation
Q11. Which enzyme in extrahepatic tissues activates acetoacetate for entry into the TCA cycle?
- HMG‑CoA lyase
- Succinyl‑CoA:3‑ketoacid CoA transferase (SCOT)
- Acetoacetate decarboxylase
- Acetyl‑CoA carboxylase
Correct Answer: Succinyl‑CoA:3‑ketoacid CoA transferase (SCOT)
Q12. Which of the following amino acids is strictly ketogenic?
- Alanine
- Leucine
- Glutamine
- Glycine
Correct Answer: Leucine
Q13. Deficiency of mitochondrial HMG‑CoA synthase in infants leads to:
- Hyperketotic hypoglycemia
- Hypoketotic hypoglycemia
- Excessive cholesterol synthesis
- Increased lactate clearance
Correct Answer: Hypoketotic hypoglycemia
Q14. Compared to glucose, ketone bodies yield ATP by being converted ultimately to:
- Pyruvate
- Oxaloacetate
- Acetyl‑CoA entering the TCA cycle
- Lactate
Correct Answer: Acetyl‑CoA entering the TCA cycle
Q15. Which clinical drug class has been associated with euglycemic DKA as an adverse effect?
- SGLT2 inhibitors
- Statins
- ACE inhibitors
- Beta‑blockers
Correct Answer: SGLT2 inhibitors
Q16. During prolonged fasting, the brain adapts to ketone utilization because:
- Ketones require insulin for uptake
- Glucose transporters increase expression
- Ketone bodies cross the blood‑brain barrier and provide acetyl‑CoA
- Ketones directly convert to glucose
Correct Answer: Ketone bodies cross the blood‑brain barrier and provide acetyl‑CoA
Q17. Which laboratory measurement is most reliable for assessing current ketotic state in blood?
- Urine nitroprusside test
- Plasma β‑hydroxybutyrate concentration
- Serum acetone concentration
- Serum triglycerides
Correct Answer: Plasma β‑hydroxybutyrate concentration
Q18. Excessive fatty acid oxidation increases hepatic NADH, which favors formation of:
- Acetoacetate over β‑hydroxybutyrate
- β‑Hydroxybutyrate over acetoacetate
- Only acetone formation
- Increased malonyl‑CoA synthesis
Correct Answer: β‑Hydroxybutyrate over acetoacetate
Q19. Which pathway competes with ketogenesis for acetyl‑CoA in the liver?
- Gluconeogenesis
- Cholesterol synthesis via cytosolic HMG‑CoA reductase
- Glycogenolysis
- Pentose phosphate pathway
Correct Answer: Cholesterol synthesis via cytosolic HMG‑CoA reductase
Q20. Which statement about acetone is correct?
- Acetone is the major energy substrate for muscle
- Acetone is metabolically inactive and excreted in breath and urine
- Acetone is converted back to acetoacetate in the liver
- Acetone is measured by β‑hydroxybutyrate assays
Correct Answer: Acetone is metabolically inactive and excreted in breath and urine
Q21. Which metabolic change decreases ketone body formation?
- High glucagon levels
- Enhanced lipolysis
- Increased insulin signaling
- Elevated free fatty acids
Correct Answer: Increased insulin signaling
Q22. Which experimental therapeutic approach raises circulating ketone bodies for neurological benefit?
- High carbohydrate diet
- Medium‑chain triglyceride (MCT) supplementation or ketogenic diet
- Cholesterol‑lowering statin therapy
- Sodium bicarbonate infusion
Correct Answer: Medium‑chain triglyceride (MCT) supplementation or ketogenic diet
Q23. Which of the following is NOT a ketogenic substrate?
- Leucine
- Lysine
- Alanine
- Acetoacetate
Correct Answer: Alanine
Q24. SCOT deficiency would most likely result in:
- Inability of the liver to synthesize ketone bodies
- Inability of extrahepatic tissues to utilize ketone bodies, causing energy deficiency
- Excessive ketone clearance by kidneys
- Increased cholesterol synthesis
Correct Answer: Inability of extrahepatic tissues to utilize ketone bodies, causing energy deficiency
Q25. Which metabolic measurement defines severe ketosis associated with DKA (approximate blood ketone level)?
- <0.6 mmol/L
- 0.5–1.0 mmol/L
- >3.0 mmol/L
- 10–15 mmol/L
Correct Answer: >3.0 mmol/L
Q26. Alcoholic ketoacidosis commonly occurs due to:
- Excess insulin secretion
- Prolonged starvation, low insulin, and increased NADH from ethanol metabolism
- Excess carbohydrate intake
- Inhibition of lipolysis
Correct Answer: Prolonged starvation, low insulin, and increased NADH from ethanol metabolism
Q27. Which enzyme converts β‑hydroxybutyrate back to acetoacetate in peripheral tissues?
- 3‑hydroxybutyrate dehydrogenase
- Acetoacetate decarboxylase
- HMG‑CoA lyase
- Acetyl‑CoA synthetase
Correct Answer: 3‑hydroxybutyrate dehydrogenase
Q28. In ketone utilization, acetoacetate is ultimately converted to acetyl‑CoA via which intermediate?
- Acetoacetyl‑CoA
- Pyruvate
- Succinyl‑CoA
- Malonyl‑CoA
Correct Answer: Acetoacetyl‑CoA
Q29. Which of the following increases hepatic ketone production during fasting?
- Activation of pyruvate dehydrogenase
- High levels of malonyl‑CoA
- Elevated hormone‑sensitive lipase activity in adipose tissue
- High insulin/glucagon ratio
Correct Answer: Elevated hormone‑sensitive lipase activity in adipose tissue
Q30. Which laboratory finding is typical in DKA besides elevated ketones?
- Metabolic alkalosis
- Hyperchloremic metabolic acidosis with normal anion gap
- High anion gap metabolic acidosis and hyperglycemia
- Hypoglycemia and respiratory alkalosis
Correct Answer: High anion gap metabolic acidosis and hyperglycemia
Q31. Which lipid transport change favors ketogenesis?
- Inhibition of adipose lipolysis
- Increased release of free fatty acids to the liver
- Enhanced dietary carbohydrate absorption
- Upregulation of fatty acid synthase
Correct Answer: Increased release of free fatty acids to the liver
Q32. What is the effect of malonyl‑CoA on carnitine palmitoyltransferase I (CPT1) and ketogenesis?
- Malonyl‑CoA activates CPT1 and increases ketogenesis
- Malonyl‑CoA inhibits CPT1 and decreases ketogenesis
- Malonyl‑CoA has no effect on CPT1
- Malonyl‑CoA converts into ketone bodies directly
Correct Answer: Malonyl‑CoA inhibits CPT1 and decreases ketogenesis
Q33. Which statement about nutritional ketosis (e.g., ketogenic diet) is true?
- Blood ketone levels are typically >10 mmol/L
- It results in mild to moderate elevations of β‑hydroxybutyrate (0.5–3 mmol/L)
- It is indistinguishable from DKA clinically
- It suppresses fatty acid oxidation
Correct Answer: It results in mild to moderate elevations of β‑hydroxybutyrate (0.5–3 mmol/L)
Q34. Which coenzyme is required by acetoacetyl‑CoA thiolase in ketone synthesis or utilization?
- NAD+
- FAD
- Coenzyme A (CoA‑SH)
- NADP+
Correct Answer: Coenzyme A (CoA‑SH)
Q35. Which of the following best describes ketone body polarity and solubility?
- Highly lipophilic and require chylomicrons for transport
- Water‑soluble and transported in plasma without carriers
- Insoluble and stored in adipose tissue
- Bound to albumin for transport
Correct Answer: Water‑soluble and transported in plasma without carriers
Q36. Which pathological state produces hypoketotic hypoglycemia due to impaired fatty acid oxidation?
- Medium‑chain acyl‑CoA dehydrogenase (MCAD) deficiency
- Type 1 diabetes mellitus
- SGLT2 inhibitor therapy
- Prolonged fasting
Correct Answer: Medium‑chain acyl‑CoA dehydrogenase (MCAD) deficiency
Q37. Which ketone is predominantly measured in point‑of‑care blood ketone meters?
- Acetone
- β‑Hydroxybutyrate
- Acetoacetate
- Acetyl‑CoA
Correct Answer: β‑Hydroxybutyrate
Q38. What effect does increased hepatic NADH/NAD+ ratio have on ketone body composition?
- Favors conversion of acetoacetate to β‑hydroxybutyrate
- Favors oxidation of β‑hydroxybutyrate to acetoacetate
- Prevents ketogenesis entirely
- Increases acetone to acetoacetate conversion
Correct Answer: Favors conversion of acetoacetate to β‑hydroxybutyrate
Q39. Which statement about ketone bodies and myocardial metabolism is correct?
- Heart cannot use ketone bodies for energy
- Myocardium readily oxidizes ketone bodies, especially during fasting or heart failure
- Ketone bodies are toxic to cardiac tissue
- Ketone bodies are converted to glycogen in the heart
Correct Answer: Myocardium readily oxidizes ketone bodies, especially during fasting or heart failure
Q40. Which enzymatic defect would increase urinary excretion of ketone bodies?
- Hepatic glucokinase deficiency
- Impaired renal ketone reabsorption
- Excess SCOT activity
- Increased HMG‑CoA reductase
Correct Answer: Impaired renal ketone reabsorption
Q41. Which metabolic fuel becomes quantitatively important for the brain after ~3 days of starvation?
- Glucose only
- Lactate
- Ketone bodies (β‑hydroxybutyrate and acetoacetate)
- Free fatty acids
Correct Answer: Ketone bodies (β‑hydroxybutyrate and acetoacetate)
Q42. Which therapeutic agent increases ketone production by promoting fatty acid oxidation when carbohydrate intake is restricted?
- Insulin infusion
- Medium‑chain triglyceride (MCT) oil
- High‑dose glucagon receptor blocker
- Niacin (vitamin B3)
Correct Answer: Medium‑chain triglyceride (MCT) oil
Q43. Which clinical sign is most specific for acetone accumulation in ketosis?
- Fruity odor of breath
- Jaundice
- Peripheral edema
- Bradycardia
Correct Answer: Fruity odor of breath
Q44. Which metabolic pathway produces acetyl‑CoA used for ketogenesis during fasting?
- Glycolysis
- Beta‑oxidation of fatty acids
- Pentose phosphate pathway
- De novo lipogenesis
Correct Answer: Beta‑oxidation of fatty acids
Q45. Which statement about the role of insulin in ketone metabolism is true?
- Insulin stimulates hormone‑sensitive lipase and increases ketogenesis
- Insulin inhibits lipolysis, decreasing substrate supply for ketogenesis
- Insulin directly activates HMG‑CoA lyase
- Insulin increases malonyl‑CoA removal to favor ketogenesis
Correct Answer: Insulin inhibits lipolysis, decreasing substrate supply for ketogenesis
Q46. Which diagnostic approach helps distinguish DKA from alcoholic ketoacidosis?
- Serum glucose levels (DKA: markedly elevated; alcoholic ketoacidosis: normal or low)
- Presence of urinary glucose only in alcoholic ketoacidosis
- Acetone absent in alcoholic ketoacidosis
- Blood ketones are only elevated in DKA
Correct Answer: Serum glucose levels (DKA: markedly elevated; alcoholic ketoacidosis: normal or low)
Q47. Which enzyme converts HMG‑CoA to acetoacetate in mitochondria?
- HMG‑CoA lyase
- HMG‑CoA reductase
- HMG‑CoA synthase (cytosolic)
- Acetyl‑CoA carboxylase
Correct Answer: HMG‑CoA lyase
Q48. Which statement about therapeutic ketone esters is correct?
- They decrease circulating ketone concentrations
- They provide exogenous ketones that raise blood β‑hydroxybutyrate levels
- They are contraindicated in ketogenic diets
- They inhibit monocarboxylate transporters
Correct Answer: They provide exogenous ketones that raise blood β‑hydroxybutyrate levels
Q49. Which metabolic consequence is typical when β‑hydroxybutyrate predominates over acetoacetate?
- Lower reduction state (low NADH)
- Higher hepatic NADH/NAD+ ratio indicating more reduced state
- Increased gluconeogenesis from ketones
- Enhanced SCOT activity in the liver
Correct Answer: Higher hepatic NADH/NAD+ ratio indicating more reduced state
Q50. Which clinical intervention is essential in initial management of DKA to reduce ketone production?
- Immediate high‑dose steroid administration
- Rapid correction with insulin to suppress lipolysis and ketogenesis
- Exclusive oral carbohydrate intake
- Administration of SGLT2 inhibitors
Correct Answer: Rapid correction with insulin to suppress lipolysis and ketogenesis
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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