Norvaline transamination

Thus we designed and synthesized a bicyclic pyridoxamine derivative carrying an oriented catalytic side arm (16) [11], Rates for conversion of the ketimine Schiff base into the aldimine, formed with 26 (below) and a-ketovaleric acid, indolepyruvic acid, or pyruvic acid, were enhanced 20-30 times relative to those carried out in the presence of the corresponding pyridoxamine derivatives without the catalytic side arm. With a-ketovaleric acid, 16 underwent transamination to afford D-norvaline with 90% ee. The formation of tryptophan and alanine from indolepyruvic acid and pyruvic acid, respectively, showed a similar preference. A control compound (17), with a propylthio group at the same stereochemical position as the aminothiol side arm in 16, produced a 1.5 1 excess of L-norvaline, in contrast to the large preference for D-amino acids with 16. Therefore, extremely preferential protonation seems to take place on the si face when the catalytic side arm is present as in 16. 

Complex formation towards 1,8-ANS and 2,7-naphthalene diol 36) has been studi l also for the macrocycles 45 and 46, which are homologous to 47 By affixing a pyridoxamine side chain to 46, the host 58 was obtained. The catalytic activity in the transamination of phenylpyruvate (59) to phenylalanine 60) and of a-ketovalerianic acid 61) to norvaline 62) was studied using this host. 

Norvaline is strongly ketogenic. The L-form is attacked by L-amino acid oxidase and the D-form by D-amino acid oxidase. Its susceptibility to transamination has not been reported. Its ready oxidation to CO2 in the intact animal has been observed by Hassan and Greenberg. More of this amino acid is excreted unchanged in the urine than is leucine. Evidence for the formation of a 2-carbon unit was also obtained in this work. This leads to the scheme for the catabolism of norvaline shown in Fig. 8. 

Rudman and Meister IJ ) first showed the presence of a transaminase in cell-free extracts of E. colt that catalyze transamination reactions between glutamate and isoleucine, valine, leucine, norleucine, and norvaline. These monocarboxylic amino acids transaminated with each other as well as with glutamine. Preparations of an E. cdi mutant which did not respond to a-keto- 8-methylvalerate was unable to transaminate isoleucine or valine. The transaminase responsible for activity with the branched-chain amino acids was separated from other transaminases and considerably purified by standard methods of protein purification. It was shown to... 

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