Covalent binding of a mercaptan S-sulfate to hepatic cytosolic proteins and its inhibition by glutathione

Abstract

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.