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4.3.7.Formation of ketone bodies
Formation of ketone bodies
Excess acetyl-CoA released on oxidation of fatty acids and not required by the liver is converted into the ketone bodies, acetoactate and D-β-hydroxy butyrate, which are circulated via the blood to peripheral tissues, to be used as fuel for the citric acid cycle. The ketone bodies may be regarded as a transport form of acetyl groups. They can supply significant fraction of the energy to some peripheral tissues, up to one-third in the case of the heart
Ketone bodies are formed in the liver but utilized in the extrahepatic tissue. Enzymes responsible are associated with mitochondria. Two units of acetyl CoA formed in β-oxidation of fatty acids condence to form acetoacetyl CoA by a reversal of thiolase reaction. Two pathways exist for the formation of acetoacetone.
1. Action of acetoacetyl CoA deacylase: There is simple deacylation catalysed by the enzyme acetoacetyl CoA deacylase.
2. Action of HMG-CoA: The acetoacetyl CoA condense with another molecule of acetyl CoA to form β-hydroxy β-methyl glutaryl CoA by HMG CoA synthase.
3. Action of HMG CoA lyase: β-hydroxy β-methyl glutaryl CoA is splitted into acetoacetic acid and acetyl CoA by HMG CoA lyase present in mitochondria. From acetoacetic acid, acetone and βhydroxyl butyrate are formed.
These compounds are carried from liver to extrahepatic tissue mainly kidney and muscle where they are oxidized for energy production afte conversion to acetyl Co A. Ketone body formation occurs if the concentration of circulating free fatty acids increases by the lipolysis of triglycerides in adipose tissue.