Studies in valine biosynthesis. III. Biological distribution of a dihydroxy acid dehydrase.

The steps in the pathway of formation of valine are: decarbosylation of pyruvate to an acetaldehyde-thiamine pyrophosphate intermediate which condenses with another molecule of pyruvate to yield ar-acetolactic acid, migration of the a-methyl carbon to form ar-keto-fl-hydroxyisovaleric acid, reduction of this acid to produce (Y ,&dihydroxyisovaleric acid, dehydration to yield ar-ketoisovaleric acid, and, finally, transamination to form valine. The reactions in the biogenesis of isoleucine are parallel to those of valine. Instead of pyruvate, oc-ketobutyrate condenses with acetaldehyde to form or-hydroxy-cr-acetylbutyric acid. Migration of the ethyl group from the a! to the p position gives the carbon skeleton of isoleucine. Reduction and dehydration yield the keto acid analogue of isoleucine. These pathways have been demonstrated primarily with Neurospora crassa, Escherichia co&i, and Saceharomyces cerevisiae (cf. l-4). The last biosynthetic step for these two amino acids is transamination, a reaction that is known to occur in mammalian tissues. With the exception of threonine and lysine, each of the essential amino acids can be replaced by their corresponding cY-keto acid analogues for a growth response in weanling rats (5). Similar nutritional relationships have been observed in lactic acid bacteria (6). Therefore, it was desirable to test mammalian tissues and lactic acid bacteria for the possible presence of the next to last step of valine biosynthesis, namely the dehydration reaction. As a clue to the valine pathway, the presence of the dihydroxy acid dehydrase has been briefly reported in four new microorganisms (7) and higher plants (4) .I Herein is presented evidence for an even more widespread distribution of the dehydrase in those microorganisms that can grow on ammonium salts. In contrast to lysine and ornithine biosynthesis, the reported and cited investigations are consistent with a single pathway in the two terminal steps of valine biosynthesis.