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 (hGSTP1-1), 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 been determined. The kcat/Km values for hGSTP1-1 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±3 mM−1 s−1, respectively. The catalytic efficiencies of the hGSTP1-1 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 hGSTP1-1 isoforms IA, IV, VA and VV toward crotonaldehyde (16±2, 12±1, 17±2, and 12±2 mM−1s−1, respectively) were not statistically significantly different from each other. Our results suggest that hGSTP1-1 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.