Catalytic efficiencies of allelic variants of human glutathione S-transferase Pi in the glutathione conjugation of alpha,beta-unsaturated aldehydes

The catalytic efficiencies of the allelic variants of human glutathione (GS H) S-transferase Pi (hGSTPI-1), which differ in their primary structures by the amino acids in positions 104 (isoleucine or valine) and/or 113 (alanin e or valine), in the GSH conjugation (detoxification) of acrolein and croto naldehyde have bren determined. The k(cat)/K-m values for hGSTPI-1 isoforms I104,A113 (IA), I104,V113 (IV), V104,A113 (VA) and V104,V113 (VV) toward a crolein were 129 +/- 3, 116 +/- 3, 128 +/- 4 and 92 +/- 4 mM(-1) s(-1), res pectively. The catalytic efficiencies of the hGSTPI-1 variants IA, IV, and VA in the GSH conjugation of acrolein were statistically significantly high er (at P = 0.05) compared with the VV isoform. On the other hand, the catal ytic efficiencies of the hGSTPI-1 isoforms IA, IV, VA and VV toward crotona ldehyde (16 +/- 2, 12 +/- 1, 17 +/- 2, and 13 +/- 2 mM(-1)s(-1), respective ly) were not statistically significantly different from each other. Our res ults suggest that hGTSTPI-1 polymorphism may be an important factor in diff erential susceptibility of individuals to the toxic effects of acrolein, wh ich is a widely spread environmental pollutant and generated endogenously d uring metabolic activation of anticancer drug cyclophosphamide. (C) 2000 El sevier Science Ireland Ltd. All rights reserved.