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I. Frequently Asked Questions about Fatty Acid Metabolism

                                                           

Ketone Bodies: Answer

Where are ketone bodies made? Where are they used? What accounts for this difference?

Ketone bodies are synthesized in the liver mitochondria, which is where HMG CoA lyase is expressed. This is the enzyme that cleaves HMG CoA, forming acetoacetate and acetyl CoA. (In endoplasmic reticulum of liver and most other cells, in contrast, HMG CoA reductase is found, which converts HMG CoA to mevalonate, a precursor of the isoprenoids and the steroids.)

Ketone bodies are used by most aerobic tissues, particularly heart and muscle. The major enzyme for activating acetoacetate is the mitochondrial enzyme, succinyl CoA: 3-ketoacid CoA transferase. This enzyme is not found in the liver. Hence the liver is a net exporter of ketone bodies.