Isovaleryl coenzyme

Matsubara, Y, Indo, Y, Naito, E., Ozasa, H., Glassberg, R., Vockley, J., Ikeda, Y, Kraus, J. Tanaka, K. (1989) J. Biol. Chem. 264, 16321—16331. Molecular cloning and nucleotide sequence of cDNAs encoding the precursors of rat long chain acyl-coenzymeA, short chain acyl-coenzyme A, and isovaleryl-coenzyme A dehydrogenases. Sequence homology of four enzymes of the acyl-CoA dehydrogenase family. 

The inborn errors of L-leucine catabolism present biochemically with branched-chain amino and/or organic aciduria [1]. These disorders include maple syrup disease (MSD branched-chain a-ketoacid dehydrogenase (BCKD) deficiency), isovaleric acidemia (isovaleryl-coenzyme A (CoA) dehydrogenase deficiency), isolated 3-methylcrotonyl-CoA carboxylase deficiency, the 3-methylglutaconic acidurias (3-methylglutaconyl-CoA hydratase deficiency, Barth syndrome, and other disorders in which the primary defect has not been demonstrated), and 3-hydroxy-3-methylglutaric aciduria (3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency). 

The normal branched chain isovaleryl CoA (149) is then desaturated to the a,)3-enonyl CoA (150) by a flavin-linked branched chain acyl CoA dehydrogenase (equation 24). When the methylenecyclopropane acyl CoA (151) is exposed to acyl CoA dehydrogenase, time-dependent inactivation ensues with covalent modification of the bound FAD coenzyme (equation 25), possibly via a 6,5-adduct although the structure is unproven. ... 

Fig. 6.1. The L-leucine degradative pathway. Reactions for which inherited metabolic disorders have not been conclusively identified include A, leucine-isoleucine aminotransferase and the majority of the 3-methylglutaconic acidurias (6.6-6.7). 6.1, Branched-chain a-ketoacid dehydrogenase (BCKD) complex, a reaction also occurring in the initial steps of L-isoleucine and L-valine degradation 6.2, isovaleryl-CoA dehydrogenase 6.3, 3-methylcrotonyl-CoA carboxylase 6.4, 3-methylglutaconyl-CoA hydra-tase 6.8, HMG-CoA lyase. Pathologic urinary metabolites used as specific markers in the differential diagnosis are presented in squares. Abbreviation Co A, coenzyme A...

FIGURE 13.2 The role of BCAAs in energy metabolism. Following removal of their amino group by reversible transamination (a) and the irreversible decarboxylation of the resulting branched-chain a-keto acids to form coenzyme A (CoA) compounds (b), BCAAs act as precursors of acetyl CoA and tricarboxylic acid cycle intermediates. CoA-SH, reduced form of CoA IB-CoA, isobutyryl-CoA ILE, isoleucine IV-CoA, isovaleryl-CoA KIC, a-ketoiso-caproate KIV, a-ketoisovalerate KMV, a-keto-P-methylvalerate LEU, leucine MB-CoA, a-methylbutyryl-CoA NADHj, reduced nicotinamide adenine dinucleotide VAL, valine. 

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