title: Microsomal formation of S-nitrosoglutathione from organic nitrites: possible role of membrane-bound glutathione transferase.
abstract: The formation of S-nitrosoglutathione (GSNO) from amyl nitrite and n-butyl nitrite was studied in rat liver microsomes, employing N-ethylmaleimide (MalNEt) as an activator and indomethacin as an inhibitor of microsomal glutathione S-transferase (GST). Rates were compared with GST activity measured with 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. MalNEt stimulated GST activity and the formation of GSNO from amyl nitrite and n-butyl nitrite about 10-fold. Increasing concentrations of indomethacin inhibited both reactions in parallel. N-Acetyl-L-cysteine but not L-cysteine could substitute for GSH. It is concluded that rat liver microsomal GST catalyses the formation of GSNO from amyl nitrite and n-butyl nitrite. The activity of the MalNEt-stimulated microsomal GST is calculated to be about 17 units/mg of enzyme with the alkyl nitrites and about 16 units/mg of enzyme with CDNB as a substrate, assuming that 3% of microsomal protein is GST. These rates are comparable with those obtained for cytosolic GSTs. Thus microsomal GST may play a significant role in the metabolism of alkyl nitrites in biological membranes.
authors.affiliation: Institut für Physiologische Chemie I, Heinrich-Heine Universität Düsseldorf, Federal Republic of Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Ji
authors.forename: T P
authors.initials: TP
authors.lastname: Akerboom
authors.forename: H
authors.initials: H
authors.lastname: Sies
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D009573:Nitrites; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D026422:S-Nitrosoglutathione; D005982:Glutathione Transferase; D005978:Glutathione