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Acetoacetyl CoA is the precursor of HMG-CoA in the mevalonate pathway, which is essential for cholesterol biosynthesis. It also takes a similar role in the ketone bodies synthesis pathway of the liver. In the ketone bodies digestion pathway , it is no longer associated with having HMG-CoA as a product or as a reactant.
It is created from acetyl-CoA, a thioester, which reacts with the enolate of a second molecule of acetyl-CoA in a Claisen condensation reaction, and it is acted upon by HMG-CoA synthase to form HMG-CoA. During the metabolism of leucine, this last reaction is reversed. Some individuals may experience Acetoacetyl-CoA deficiency. This deficiency is classified as a disorder ketone body and isoleucine metabolism that can be inherited.
Additionally, it reacts with NADPH-dependent acetoacetyl-coenzyme A reductase, also known as PhaB, in a pathway that produces polyester polyhydroxyalkanoate. The reduction of acetoacetyl-coA by Pha creates -3-hydroxybutyryl-CoA, which polymerizes to PHA. The pathway is present in bacteria such as Ralstonia eutropha and the PCC6803 strain of Synechocystis.