During prolonged starvation (>3 weeks), the brain adapts to use ketone bodies as its primary fuel, reducing its glucose requirement. Which enzyme in astrocytes and neurons converts acetoacetate to acetoacetyl-CoA to enter the TCA cycle?

• A HMG-CoA synthase
• B Beta-hydroxybutyrate dehydrogenase only
• C 3-Ketoacyl-CoA transferase (succinyl-CoA:3-ketoacid-CoA transferase, SCOT) ✓
• D Acetoacetate decarboxylase

Explanation

Ketone body utilisation in extra-hepatic tissues requires SCOT (succinyl-CoA:3-ketoacid-CoA transferase), which transfers CoA from succinyl-CoA to acetoacetate, producing acetoacetyl-CoA and succinate. Acetoacetyl-CoA is then split by thiolase into two acetyl-CoA molecules for the TCA cycle. SCOT is present in brain, heart, kidney, and skeletal muscle but absent in the liver — the liver cannot utilise its own ketone bodies. Beta-hydroxybutyrate dehydrogenase converts beta-hydroxybutyrate to acetoacetate (a prerequisite step), but the key step forming acetoacetyl-CoA is SCOT. HMG-CoA synthase is involved in ketone body synthesis (mitochondrial form) and cholesterol synthesis (cytosolic form).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.