ABSTRACT

Valine, isoleucine, and leucine, amino acids with a characteristic methyl group branching of their carbon skeleton (Figures 28.1 through 28.3), constitute the group of branched-chain amino acids (BCAA). BCAAs are essential amino acids for mammals since there is no anabolism of their carbon skeleton in mammalian tissues. Therefore, the metabolism of BCAAs, widespread among mammalian cells, includes intermediary metabolism and catabolism. Depending on the metabolic context, the rst, reversible step of BCAA degradation is a transamination reaction (step A in Figures 28.1 through 28.3). This can be considered as the intermediary metabolism of BCAAs and their corresponding branched-chain 2-oxo acids (branched-chain α-keto acids [BCKAs]). The next reaction is catalyzed by the BCKA dehydrogenase complex (BCKDH; step B in Figures 28.1 through 28.3). These two enzymes comprise the rst stage of the catabolic pathways of BCAAs. In the second stage of the catabolic pathways, the carbon skeletons of BCAAs are eventually fragmented, giving rise to propionyl-CoA, acetyl-CoA, and acetoacetate. These three compounds are valuable substrates for brain energy metabolism. Propionyl-CoA is a catabolite of both valine (Figure 28.1) and isoleucine (Figure 28.2), while the degradation of leucine and isoleucine gives rise to acetyl-CoA

28.1 Introduction to the Metabolism of Branched-Chain Amino Acids ......................................403 28.2 Metabolism of BCAAs in the Brain .....................................................................................407