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Ketone body formation

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Ketone body formation occurs as an alternative energy source during times of prolonged stress e.g. starvation. It occurs in the liver from an initial substrate of:

  • long chain fatty acids; the fatty acids undergo beta-oxidation by their normal pathway within mitochondria until acetyl-CoA is produced, or
  • ketogenic amino acids; amino acids such as leucine and lysine, released at times of energy depletion, are interconverted only to acetyl-CoA

Then, three molecules of acetyl-CoA are effectively joined together in three enzyme steps sequentially catalyzed by:

  • acetyl CoA acetyltransferase
  • HMG-CoA transferase
  • HMG-CoA lyase

Coenzyme A is regenerated and the ketone body acetoacetate is formed. Finally, acetoacetate is reduced to another ketone body, D-3-hydroxybutyrate, in a reaction catalyzed by 3-hydroxybutyrate dehydrogenase. This requires NADH. The oxidate state of the liver is such that the forward reaction is generally favoured; this results in more hydroxybutyrate being formed than acetoacetate.

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