During prolonged fasting (>72 hours), the brain adapts to use ketone bodies as the primary energy substrate. This adaptation involves upregulation of which enzyme in astrocytes and neurons?

• A HMG-CoA synthase (mitochondrial)
• B β-Hydroxybutyrate dehydrogenase
• C Succinyl-CoA:3-oxoacid CoA transferase (SCOT) ✓
• D Acetoacetyl-CoA thiolase

Explanation

Ketone body utilisation in peripheral tissues (including brain) requires SCOT (succinyl-CoA:3-oxoacid CoA transferase, also called 3-oxoacid CoA transferase), which catalyses the transfer of CoA from succinyl-CoA to acetoacetate, forming acetoacetyl-CoA. Acetoacetyl-CoA is then cleaved by thiolase to two acetyl-CoA for the TCA cycle. SCOT is absent in the liver (preventing futile cycling), explaining why the liver cannot utilise ketone bodies it produces. During prolonged fasting, SCOT is upregulated in brain, heart and skeletal muscle. HMG-CoA synthase (mitochondrial) is the key enzyme in ketone body synthesis (in liver), not utilisation. β-hydroxybutyrate dehydrogenase converts β-hydroxybutyrate to acetoacetate and is a prerequisite step.

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

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