Acetoacetyl-coenzyme A (acetoacetyl-CoA) is a precursor to HMG-CoA in the isoprenoid pathway.[1],[2] It is reversibly converted to acetyl-CoA by acetoacetyl-CoA thiolase in the mitochondria. Acetoacetyl-CoA thiolase (T2) deficiency results in a build-up of ketone bodies leading to intermittent ketoacidosis.[3],[4] Acetoacetyl-CoA is also an intermediate in the microbial biosynthesis of polyhydroxybutyrate.[5]
References:
[1]. Lynen, F., and Ochoa, S. Enzymes of fatty acid metabolism. Biochem. Biophys. Acta. 12(1-2), 299-314 (1953).
[2]. Miziorko, H.M. Enzymes of the mevalonate pathway of isoprenoid biosynthesis. Arch. Biochem. Biophys. 505(2), 131-143 (2011).
[3]. Daum, R.S., Scriver, C.R., Mamer, O.A., et al. An inherited disorder of isoleucine catabolism causing accumulation of alpha-methylacetoacetate and alpha-methyl-beta -hydroxybutyrate, and intermittent metabolic acidosis. Pediatr. Res. 7(3), 149-160 (1973).
[4]. Fukao, T., Scriver, C.R., and Kondo, N. The clinical phenotype and outcome of mitochondrial acetoacetyl-CoA thiolase deficiency (β-ketothiolase or T2 deficiency) in 26 enzymatically proved and mutation-defined patients. Mol. Genet. Metab. 72(2), 109-114 (2001).
[5]. Jacquel, N., Lo, C.-W., Wei, Y.-H., et al. Isolation and purification of bacterial poly(3-hydroxyalkanoates). Biochem. Eng. J. 39(1), 15-27 (2008).

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