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

The catalytic efficiencies of the allelic variants of human glutathione (GSH) S-transferase Pi (hGSTPI-1), which differ in their primary structures by the amino acids in positions 104 (isoleucine or valine) and/or 113 (alanine or valine), in the GSH conjugation (detoxification) of acrolein and crotonaldehyde 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 acrolein were 129 +/- 3, 116 +/- 3, 128 +/- 4 and 92 +/- 4 mM(-1) s(-1), respectively. The catalytic efficiencies of the hGSTPI-1 variants IA, IV, and VA in the GSH conjugation of acrolein were statistically significantly higher (at P = 0.05) compared with the VV isoform. On the other hand, the catalytic efficiencies of the hGSTPI-1 isoforms IA, IV, VA and VV toward crotonaldehyde (16 +/- 2, 12 +/- 1, 17 +/- 2, and 13 +/- 2 mM(-1)s(-1), respectively) were not statistically significantly different from each other. Our results suggest that hGTSTPI-1 polymorphism may be an important factor in differential susceptibility of individuals to the toxic effects of acrolein, which is a widely spread environmental pollutant and generated endogenously during metabolic activation of anticancer drug cyclophosphamide. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.