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Synthesis and Degradation of Ketone Bodies
Last Updated: 2020-09-27
Ketone bodies are water-soluble compounds that are produced when fatty acids are broken down during metabolism as by-products. They can be used as a source of energy in the heart and the brain and serve as an important energy source during fasting. The use of ketone bodies in the body has two key parts: ketogenesis and ketolysis, both which occur within the mitochondrial matrix. The former is mediated primarily by 2 key enzymes. 3-hydroxy-3-methaglutaryl coenzyme A synthase is involved in the final major regulatory reaction in the process and condenses acetyl CoA to form 3-hydroxy-3-methylglutaryl-CoA. 3-hydroxymethyl-3-methaglutaryl-CoA lyase on the other hand catalyzes the formation of acetoacetic acid from (3S)-hydroxy-3-methylglutaryl-CoA. Ketolysis however, involves two reversible reactions that mediate activation of free acetoacetic acid from acetoacetyl-CoA and creation of acetyl-CoA to be used as energy by the body. The acetoacetate is activated to the acetoacetyl-CoA by the enzyme succinyl-CoA: 3-ketoacid-coenzyme A transferase. Acetyl CoA acetyltransferase (LD24105p) equilibrates the mitochondrial pools of acetoacetyl-CoA and acetyl-CoA. This role means that LD24105p is involved in both ketogenesis and ketolysis. Acetoacetic acid can alternatively be catalyzed by short-chain dehydrogenase/reductase to form (R)-3-hydroxybutyric acid along with NADH.
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