GLUTATHIONE-PEROXIDASE AND GLUTATHIONE-REDUCTASE ACTIVITIES TOWARDS GLUTATHIONE-DERIVED ANTIOXIDANTS

A new class of glutathione derivatives with antioxidant properties has been prepared by transformation of the NH2 group into a pyrrole ring with various substitutions at the 2 and 5 positions. Due to steric hin drance and/or hydrophobicity of the 2-5-disubstituted pyrrole ring, th e reduced glutathione derivatives are poor substrates of the glutathio ne peroxidase and do not effectively compete with GSH. The oxidized gl utathione derivatives are, in turn, relatively good substrates (Km = 1 .5 mM) of the glutathione reductase as compared to natural oxidized gl utathione (Km = 0.51 mM) but are not effective competitors of the enzy me. It can be considered that the new glutathione derivatives do not s trongly interfere with the natural enzymatic defence against fatty aci d hydroperoxides formed during an oxidative stress. (C) 1994 Academic Press, Inc.