During prolonged starvation (>48 hours), the brain adapts to use ketone bodies as its primary fuel. The rate-limiting enzyme for ketone body utilisation by the brain (and heart) is:

• A HMG-CoA synthase (mitochondrial)
• B Beta-hydroxybutyrate dehydrogenase
• C Succinyl-CoA:3-ketoacid CoA transferase (SCOT) ✓
• D Acetoacetyl-CoA thiolase

Explanation

Extrahepatic tissues (brain, heart, kidney, skeletal muscle) utilise acetoacetate for energy through: acetoacetate + succinyl-CoA → acetoacetyl-CoA + succinate, catalysed by SCOT (succinyl-CoA:3-oxoacid CoA transferase, also called 3-oxoacid CoA transferase). SCOT is the key rate-limiting enzyme for ketone body utilisation and is absent in the liver (which is why the liver cannot consume its own ketone bodies). Beta-hydroxybutyrate dehydrogenase converts beta-hydroxybutyrate to acetoacetate (the substrate for SCOT). HMG-CoA synthase is the rate-limiting enzyme for ketogenesis in the liver. Acetoacetyl-CoA thiolase cleaves the product of SCOT reaction.

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

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Written and medically reviewed by the StethoPrep medical team.