MICROSOMAL GLUTATHIONE TRANSFERASE - LIPID-DERIVED SUBSTRATES AND LIPID DEPENDENCE

Rat liver microsomal glutathione transferase was found to display glut athione peroxidase activity toward a variety of oxidized lipids. 1-lin oleoyl-2-palmitoyl phosphatidylcholine hydroperoxide, 2-linoleoyl-1-pa lmitoyl phosphatidylcholine hydroperoxide, 2-linoleoyl-1-palmitoyl pho sphatidylethanolamine hydroperoxide, and cholesteryl linoleate hydrope roxide all served as substrates (0.02, 0.04, 0.02, and 0.02 mu mol/min mg, respectively). The phospholipid hydroperoxide glutathione peroxid ase activity of the enzyme was found not to require detergent and incr eased when liposomes containing peroxidized phospholipid were fused wi th liposomes containing microsomal glutathione transferase. Methyl lin oleate ozonide serves as a very efficient substrate for the microsomal glutathione transferase, The unactivated and N-ethylmaleimide-activat ed enzyme displayed specific activities of 0.74 and 5.9 mu mol/min mg, respectively. Upon examination of a series of 4-hydroxyalk-2-enals it was found that the catalytic efficiency of the enzyme increases from the 4-hydroxyhept-2-enal up to the 4-hydroxytetradec-2-enal. The speci fic activities with the various 4-hydroxyalk-2-enals tested varied bet ween 0.28 and 0.95 mu mol/min mg. The phospholipid dependence of the m icrosomal glutathione transferase was examined in proteoliposomes form ed by cholate dialysis. Phosphatidyl choline, phosphatidyl serine, pho sphatidyl ethanolamine, and rat liver microsomal phospholipids could a ll be used successfully to reconstitute the enzyme. In conclusion, mic rosomal glutathione transferase can detoxify a number of lipid peroxid ation products as well as a fatty acid ozonide. The results imply a pr otective role for the enzyme under conditions of oxidative stress. (C) 1995 Academic Press, Inc.