Microsomal glutathione transferase: lipid-derived substrates and lipid dependence.
Rat liver microsomal glutathione transferase was found to display glutathione peroxidase activity toward a variety of oxidized lipids. 1-Linoleoyl-2-palmitoyl phosphatidylcholine hydroperoxide, 2-linoleoyl-1-palmitoyl phosphatidylcholine hydroperoxide, 2-linoleoyl-1-palmitoyl phosphatidylethanolamine hydroperoxide, and cholesteryl linoleate hydroperoxide all served as substrates (0.02, 0.04, 0.02, and 0.02 mumol/min mg, respectively). The phospholipid hydroperoxide glutathione peroxidase activity of the enzyme was found not to require detergent and increased when liposomes containing peroxidized phospholipid were fused with liposomes containing microsomal glutathione transferase. Methyl linoleate ozonide serves as a very efficient substrate for the microsomal glutathione transferase. The unactivated and N-ethylmaleimide-activated enzyme displayed specific activities of 0.74 and 5.9 mumol/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 specific activities with the various 4-hydroxyalk-2-enals tested varied between 0.28 and 0.95 mumol/min mg. The phospholipid dependence of the microsomal glutathione transferase was examined in proteoliposomes formed by cholate dialysis. Phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine, and rat liver microsomal phospholipids could all be used successfully to reconstitute the enzyme. In conclusion, microsomal glutathione transferase can detoxify a number of lipid peroxidation products as well as a fatty acid ozonide. The results imply a protective role for the enzyme under conditions of oxidative stress.
Mosialou
E
E
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Piemonte
F
F
Andersson
C
C
Vos
R M
RM
van Bladeren
P J
PJ
Morgenstern
R
R
D000818:Animals; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
D008054:Lipid Peroxides; D010743:Phospholipids; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase