Differential substrate behaviours of ethylene oxide and propylene oxide towards human glutathione transferase theta hGSTT1-1.
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.
Thier
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Institut für Arbeitsphysiologie, an der Universität Dortmund, Germany. thier@arb-phys.uni-dortmund.de
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D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005027:Ethylene Oxide / Q000378:metabolism*; D005978:Glutathione / Q000097:blood; D005982:Glutathione Transferase / Q000097:blood*; D006801:Humans; D007700:Kinetics; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology
D002273:Carcinogens; D004852:Epoxy Compounds; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D005978:Glutathione; D005027:Ethylene Oxide; C009068:propylene oxide