Isovaleryl-coenzyme A (isovaleryl-CoA) is a branched-chain acyl CoA and an intermediate in the metabolism of the essential amino acid L-leucine .[1],[2] It is formed from L-leucine by the branched-chain α-keto acid dehydrogenase (BCKAD) complex and is converted to 3-methylcrotonyl-CoA by isovaleryl-CoA dehydrogenase (IVD), an enzyme involved in the inborn error of metabolism isovaleric acidemia.[3] Isovaleryl-CoA increases the oxidation rate of the branched-chain 2-oxo acids 3-methyl-2-butanoate and 4-methyl-2-oxopentanoate in isolated rat muscle mitochondria in the absence of carnitine when used at a concentration of 1 mM.[4] It also inhibits succinate-CoA ligase activity in rat liver mitochondria (IC50 = 273 µM).[5]
References:
[1].Duan, Y., Li, F., Li, Y., et al.The role of leucine and its metabolites in protein and energy metabolismAmino Acids48(1)41-51(2016).
[2].Mohsen, A.-W.A., Anderson, B.D., Volchenboum, S.L., et al.Characterization of molecular defects in isovaleryl-CoA dehydrogenase in patients with isovaleric acidemiaBiochemistry37(28)10325-10335(1998).
[3].Mack, M., Schniegler-Mattox, U., Peters, V., et al.Biochemical characterization of human 3-methylglutaconyl-CoA hydratase and its role in leucine metabolismFEBS J.273(9)2012-2022(2006).
[4].Veerkamp, J.H., van Moerkerk, H.T.B., and Wagenmakers, A.J.M.Interaction of short-chain and branched-chain fatty acids and their carnitine and CoA esters and of various metabolites and agents with branced-chain 2-oxo acid oxidation in rat muscle and liver mitochondriaInt. J. Biochem.17(9)967-974(1985).
[5].Bergen, B.J., Stumpf, D.A., Haas, R., et al.A mechanism of toxicity of isovaleric acid in rat liver mitochondriaBiochem. Med.27(2)154-160(1982).