Malonyl coenzyme A is a coenzyme A derivative that is used in fatty acid and polyketide synthesis and in the transport of α-ketoglutarate across the mitochondrial membrane.1,2 Malonyl-CoA is formed by acetyl-CoA carboxylase-mediated carboxylation of acetyl-CoA 1 Fatty acid synthase catalyzes the NADPH-dependent condensation of malonyl-CoA and acetyl-CoA to produce palmitate. Proliferating human cancer cells upregulate this fatty acid synthesis pathway as a strategy for survival. High levels of malonyl-CoA, achieved through fatty acid synthase inhibition, have been proposed to contribute to cancer cell apoptosis.3 Manlonyl-CoA is exclusively used as the extender unit in the synthesis of bacterial aromatic polyketides.2,4
Reference
1. Hiltunen, J.K., Autio, K.J., Schonauer, M.S., et al. Mitochondrial fatty acid synthesis and respiration Biochim.Biophys.Acta. 1797(6-7), 1195-1202 (2010).
2. Summers, R.G., Ali, A., Shen, B., et al. Malonyl-coenzyme A:Acyl carrier protein acyltransferase of Streptomyces glaucescens: A possible link between fatty acid and polyketide biosynthesis Biochem. 34(29), 9389-9402 (1995).
3. Pizer, E.S., Thupari, J., Han, W.F., et al. Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts Cancer Research 60, 213-218 (2000).
4. Zhan, J. Biosynthesis of bacterial aromatic polyketides Current Topics in Medicinal Chemistry 9(17), 1598-1610 (2009).