Category: biosynthesis
Hepatic mitochondrial conversion of acetyl-CoA into ketone bodies during prolonged fasting, ketogenic diet, or insulin deficiency. Acetyl-CoA from accelerated β-oxidation condenses to acetoacetyl-CoA → HMG-CoA (via mitochondrial HMG-CoA synthase 2, the rate-limiting enzyme — distinct from the cytosolic HMGCS1 of cholesterol synthesis) → acetoacetate → β-hydroxybutyrate (the dominant circulating ketone, reduced by BDH1) or → acetone (spontaneous decarboxylation; responsible for the fruity breath of DKA). Extrahepatic tissues reverse the steps to regenerate acetyl-CoA for fuel.