Modulation of Glutathione S-Transferase Activity by a Thiol/Disulfide Exchange Reaction and Involvement of Thioltransferase

Low concentrations of cystamine and cystine inactivated human placenta glutathione S-transferase (GST-π) in cytosolic fraction very effectively, as did the purified enzyme, through the thiol/disulfide exchange reaction. Mixed disulfide formation of GST-π in cytosol was prevented by thioltransferase existing in cytosol with a low concentration of GSH. This protection of GST-π activity was more effective with the participation of glutathione reductase. The incorporation of half-[14C]cystine into a GST-π molecule according to the inactivation was provided by autoradiography. Purified human placenta thioltransferase (1900-fold from cytosol) could release the incorporated half-[14C]cystine from a GST-π molecule with restoration of enzyme activity. Thioredoxin in placenta cytosol could not protect the GST-π activity from inactivation at all.