In vitro study of the metabolic effects of D-amino acids

While the L-configuration of amino acids predominates in all known living systems, D-enantiomers of amino acids have been detected with highly sensitive chromatographic techniques in human physiological fluids. In the present study, the survival of Chinese hamster ovary cells (CHO) and HeLa cells was inhibited by exposure to high concentrations of some D- or L-amino acids. Inhibition of colony formation, though, was not necessarily observed to be chiral-dependent. Some L-amino acids (LAAs) were found to be toxic while other D-amino acids (DAAs) were innocuous in both cultures. This is contradictory to the previous observations that DAAs were generally considered to be harmful. Frequently it was implied, although not experimentally proven, that the LAAs were not toxic. One of the metabolites produced by oxidative deamination of D- or LAAs is hydrogen peroxide (H2O2), a reactive oxygen species (ROS) that is decomposed by catalase. Increased intracellular H2O2 can result in peroxidation of lipids. We measured catalase activity and the lipid peroxide levels (LPO) after incubating cells in either D- or LAAs. The amino acids (AAs) that were found to inhibit colony formation were found to be associated with higher levels of catalase activity and LPO. Therefore, we hypothesize that enhanced ROS generation may be, in part, responsible for the observed toxicity of some amino acids.