Covalent binding of a mercaptan S-sulfate to hepatic cytosolic proteins and its inhibition by glutathione.
4-Nitrobenzyl mercaptan (NBM) S-sulfate, a new type of the sulfate conjugate enzymatically formed from NBM in the presence of 3'-phosphoadenosine 5'-phosphosulfate in rat liver cytosol, bound covalently to rat liver cytosolic proteins at pH 7.4. The protein binding of NBM S-sulfate was strongly retarded by GSH. GSH not only played a role as a scavenger for NBM S-sulfate with formation of NBM and GSSG via S-(4-nitrobenzyl)thioglutathione, but also cleaved the covalent bonds, possibly disulfides formed from NBM S-sulfate and sulfhydryl groups of the cytosolic proteins. Thus, evidence was provided that NBM S-sulfate be a new type of the reactive metabolite.
D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry; D009578:Nitrobenzenes / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D013431:Sulfates / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D004220:Disulfides; D009578:Nitrobenzenes; D011506:Proteins; D013431:Sulfates; D013438:Sulfhydryl Compounds; C049559:4-nitrobenzyl mercaptan S-sulfate; D005978:Glutathione