Isoleucine discovery

Because of their unique biological functions, a significant and growing part of new drug discovery and development is focused on this class of biomolecules. Their biological functions are determined by the exact arrangement, or sequence of different amino acids in their makeup. There are 20 naturally occurring amino acids, 8 of which are essential amino acids, namely, l-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-valine, l-threonine, and L-tryptophan. 

Key discoveries leading to the elucidation of the pathways of biosynthesis of valine and isoleucine were the isolation of the dihydroxy precursors, a,j9-dihydrox3dsovaleric acid and a, 8-dihydroxy-/3-methylvaleric acid (141, 10), the transamination between the a-keto analogs of these amino acids and glutamic acid 10), and isotopic labeling that was consistent with the conclusion that valine biossmthesis was initiated by a condensation of two molecules of P3mivic acid and isoleucine biosynthesis by a corresponding... 

Pyruvate decarboxylase is able to catalyze two different reactions the nonoxidative decarboxylation of a-keto acids to the corresponding aldehydes [10,15-17] and a car-boxyligase side reaction leading to the formation of hydroxy ketones [18,19]. An understanding of why the last reaction is catalyzed by pyruvate decarboxylase, the physiological role of which is to decarboxylate pyruvate to acetaldehyde, was revealed by the discovery that pyruvate decarboxylase is homologous with acetolactate synthase [20], the enzyme catalyzing an acyloin condensation in the first step of isoleucine-valine biosynthesis. 

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