Biological Implications of Oxidation and Unidirectional Chiral Inversion of D-amino Acids

Yong-Xiang      Wang; Nian      Gong; Yan-Fei      Xin; Bin      Hao; Xiang-Jun      Zhou; Catherine      C.Y. Pang

doi:10.2174/138920012799320392

Abstract

Recent progress in chiral separation of D- and L-amino acids by chromatography ascertained the presence of several free Damino acids in a variety of mammals including humans. Unidirectional chiral inversion of many D-amino acid analogs such as exogenous NG-nitro-D-arginine (D-NNA), endogenous D-leucine, D-phenylanine and D-methionine have been shown to take place with inversion rates of 4-90%, probably dependent on various species D-amino acid oxidase (DAAO) enzymatic activities. DAAO is known to catalyze the oxidative deamination of neutral and basic D-amino acids to their corresponding α-keto acids, hydrogen peroxide and ammonia, and is responsible for the chiral inversion. This review provides an overview of recent research in this area: 1) oxidation and chiral inversion of several D-amino acid analogs in the body; 2) the indispensable but insufficient role of DAAO particularly in the kidneys and brain for the oxidation and chiral inversion of D-amino acids analogs; and 3) unidentified transaminase(s) responsible for the second step of chiral inversion. The review also discusses the physiological significance of oxidation and chiral inversion of D-amino acids, which is still a subject of dispute.

Keywords: D-amino acid, D-amino acid oxidase (DAAO), kidney, NG-nitro-D-arginine (D-NNA), transaminase, unidirectional chiral inversion, proteinogenic amino acids, chromatography, L-configuration, racemization