IN-VITRO STUDY OF THE METABOLIC EFFECTS OF D-AMINO ACIDS

Citation
N. Ercal et al., IN-VITRO STUDY OF THE METABOLIC EFFECTS OF D-AMINO ACIDS, Chirality, 8(1), 1996, pp. 24-29
Citations number
23
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
Journal title
ISSN journal
08990042
Volume
8
Issue
1
Year of publication
1996
Pages
24 - 29
Database
ISI
SICI code
0899-0042(1996)8:1<24:ISOTME>2.0.ZU;2-P
Abstract
While the L-configuration of amino acids predominates in all known liv ing systems, D-enantiomers of amino acids have been detected with high ly sensitive chromatographic techniques in human physiological fluids. In the present study, the survival of Chinese hamster ovary cells (CH O) 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 (L AAs) were found to be toxic while other D-amino acids (DAAs) were inno cuous in both cultures. This is contradictory to the previous observat ions that DAAs were generally considered to be harmful. Frequently it was implied, although not experimentally proven, that the LAAs were no t 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 resu lt in peroxidation of lipids. We measured catalase activity and the li pid peroxide levels (LPO) after incubating cells in either D- or LAAs. The amino acids (AAs) that were found to inhibit colony formation wer e found to be associated with higher levels of catalase activity and L PO. Therefore, we hypothesize that enhanced ROS generation may be, in part, responsible for the observed toxicity of some amino acids. (C) 1 996 Wiley-Liss, Inc.