Several of the initial reactions of the catabolism of isoleucine, leucine, and valine (Figure 1) are analogous to reactions of fatty acid catabolism. Following transamination (see Figure 1, reaction 1), the carbon skeletons of the resulting α-keto acids undergo oxidative decarboxylation and conversion to coenzyme A thioesters. This multistep process is catalyzed by the mitochondrial branched-chain α-ketoacid dehydrogenase complex, whose components are functionally identical to those of the pyruvate dehydrogenase complex (PDH). Like PDH, the branched chain α-ketoacid dehydrogenase complex consists of five components.
Fig1. The first three reactions in the catabolism of leucine, valine, and isoleucine. Note the analogy of reactions 2 and 3 to reactions of the catabolism of fatty acids. The analogy to fatty acid catabolism continues, as shown in subsequent figures.
E1: thiamin pyrophosphate (TPP)-dependent branched chain α-ketoacid decarboxylase
E2: dihydrolipoyl transacylase (contains lipoamide)
E3: dihydrolipoamide dehydrogenase (contains FAD)
PDH complex kinase (PDK)
PDH complex phosphatase (PDP)
As for pyruvate dehydrogenase, the PDH complex kinase and PDH complex phosphatase regulate activity of the branched-chain α-ketoacid dehydrogenase complex via phosphorylation (inactivation) and dephosphorylation (activation).
Dehydrogenation of the resulting coenzyme A thioesters (reaction 3, Figure 1) proceeds like the dehydrogenation of lipid-derived fatty acyl-CoA thioesters . Figures 2, 3, and 4 illustrate the subsequent reactions unique for each amino acid skeleton.
Fig2. Catabolism of the β-methylcrotonyl-CoA formed froml-leucine.Asterisks indicate carbon atoms derived from CO2 .
Fig3. Subsequent catabolism of the tiglyl-CoA formed froml-isoleucine.
Fig4. Subsequent catabolism of the methacrylyl CoA formed froml-valine (see Figure 1). (α-AA, α-amino acid; α-KA, α-keto acid.)
