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

Cancer Lett. 2000 Jun 1;154(1):39-43. doi: 10.1016/s0304-3835(00)00390-6.

Abstract

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 k(cat)/K(m) 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(-1)s(-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acrolein / metabolism
  • Acrolein / toxicity
  • Aldehydes / chemistry
  • Aldehydes / metabolism*
  • Alleles
  • Catalysis
  • Dose-Response Relationship, Drug
  • Glutathione / metabolism
  • Glutathione S-Transferase pi
  • Glutathione Transferase / chemistry
  • Glutathione Transferase / genetics*
  • Glutathione Transferase / metabolism
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Kinetics
  • Polymorphism, Genetic
  • Protein Isoforms

Substances

  • Aldehydes
  • Isoenzymes
  • Protein Isoforms
  • Acrolein
  • 2-butenal
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Glutathione