Isoleucine metabolism, thiamin

The intermediary metabolism has multienzyme complexes which, in a complex reaction, catalyze the oxidative decarboxylation of 2-oxoacids and the transfer to coenzyme A of the acyl residue produced. NAD" acts as the electron acceptor. In addition, thiamine diphosphate, lipoamide, and FAD are also involved in the reaction. The oxoacid dehydrogenases include a) the pyruvate dehydrogenase complex (PDH, pyruvate acetyl CoA), b) the 2-oxoglutarate dehydrogenase complex of the tricarboxylic acid cycle (ODH, 2-oxoglutarate succinyl CoA), and c) the branched chain dehydrogenase complex, which is involved in the catabolism of valine, leucine, and isoleucine (see p. 414). 

The first step in valine biosynthesis is a condensation between pyruvate and active acetaldehyde (probably hy-droxyethyl thiamine pyrophosphate) to yield a-acetolactate. The enzyme acetohydroxy acid synthase usually has a requirement for FAD, which, in contrast to most flavopro-teins, is rather loosely bound to the protein. The very same enzyme transfers the acetaldehyde group to a-ketobutyrate to yield a-aceto-a-hydroxybutyrate, an isoleucine precursor. Unlike pyruvate, the a-ketobutyrate is not a key intermediate of the central metabolic routes rather it is produced for a highly specific purpose by the action of a deaminase on L-threonine as shown in figure 21.10. 

Thiamine pyrophosphate has two important coenzyme roles, both of which focus mostly on carbohydrate metabolism (Figs. 8.26 and 8.27). The active portion of the coen- rae is the thiazole ring. The first step in the oxidative decarboxylation of a-keto acids requires TPP. The two most common examples are pyruvate and a-ketoglutarate, oxidatively decarboxyatedto acetyl CoA and succinyl CoA, respectively. The same reaction is found in the metabolism of the branched-chain amino acids valine, isoleucine, leucine, and methionine. In all cases, TPP is a coenzyme in a mitochondrial multienzyme complex, consisting of TPP, lipoic acid, coenzyme A, FAD, and NAD. Note the number of vitamins required for the oxidative decarboxylation of a-keto acids thiamine (TPP), pantothenic acid (coenzyme A), riboflavin (FAD),and niacin (NAD). 

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