Differential substrate behaviours of ethylene oxide and propylene oxide towards human glutathione transferase theta hGSTT1-1

Arch Toxicol. 1999 Nov;73(8-9):489-92. doi: 10.1007/s002040050640.

Abstract

The transformation of ethylene oxide (EO), propylene oxide (PO) and 1-butylene oxide (1-BuO) by human glutathione transferase theta (hGSTT1-1) was studied comparatively using 'conjugator' (GSTT1 + individuals) erythrocyte lysates. The relative sequence of velocity of enzymic transformation was PO > EO >> 1-BuO. The faster transformation of PO compared to EO was corroborated in studies with human and rat GSTT1-1 (hGSTT1-1 and rGSTT1-1, respectively) expressed by Salmonella typhimurium TA1535. This sequence of reactivities of homologous epoxides towards GSTT1-1 contrasts to the sequence observed in homologous alkyl halides (methyl bromide, MBr; ethyl bromide, EtBr; n-propyl bromide, PrBr) where the relative sequence MeBr >> EtBr > PrBr is observed. The higher reactivity towards GSTT1-1 of propylene oxide compared to ethylene oxide is consistent with a higher chemical reactivity. This is corroborated by experimental data of acid-catalysed hydrolysis of a number of aliphatic epoxides, including ethylene oxide and propylene oxide and consistent with semi-empirical molecular orbital modelings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / metabolism*
  • Epoxy Compounds / metabolism*
  • Erythrocytes / drug effects
  • Erythrocytes / enzymology
  • Ethylene Oxide / metabolism*
  • Glutathione / blood
  • Glutathione Transferase / blood*
  • Humans
  • Kinetics
  • Rats
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / enzymology

Substances

  • Carcinogens
  • Epoxy Compounds
  • glutathione S-transferase T1
  • Glutathione Transferase
  • Glutathione
  • Ethylene Oxide
  • propylene oxide