Metabolism of oxidized linoleic acid by glutathione transferases: peroxidase activity toward 13-hydroperoxyoctadecadienoic acid.
The oxidation of linoleic acid produces several products with biological activity including the hydroperoxy fatty acid 13-hydroperoxyoctadecadienoic acid (13-HPODE), the hydroxy fatty acid 13-hydroxyoctadecadienoic acid (13-HODE), and the 2,4-dienone 13-oxooctadecadienoic acid (13-OXO). In the present work, the peroxidase activity of glutathione transferases (GST) A1-1, M1-1, M2-2, and P1-1(Val 105) toward 13-HPODE has been examined. The alpha class enzyme is the most efficient peroxidase while the two enzymes from the mu class exhibit weak peroxidase activity toward 13-HPODE. It was also determined that the conjugated diene 13-HODE is not a substrate for GST from the alpha and mu classes but that 13-HODE does inhibit the GST-catalyzed conjugation of CDNB by enzymes from the alpha, mu, and pi classes. Finally, both 13-HODE and 13-OXO were shown to be inducers of GST activity in HT-29 and HCT-116 colon tumor cells. These data help to clarify the role of GST in the metabolic disposition of linoleic acid oxidation products.
Seeley
Stacy K
SK
Department of Science and Math, Kettering University, Flint, MI 48504, USA.
Poposki
Julie A
JA
Maksimchuk
John
J
Tebbe
Jill
J
Gaudreau
Jon
J
Mannervik
Bengt
B
Bull
Arthur W
AW
D000097:Acetonitriles / Q000737:chemistry; D045744:Cell Line, Tumor; D004137:Dinitrochlorobenzene / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D019787:Linoleic Acid / Q000737:chemistry*; D008041:Linoleic Acids / Q000737:chemistry*; D008042:Linolenic Acids / Q000737:chemistry*; D008054:Lipid Peroxides / Q000737:chemistry*; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism*; D009195:Peroxidase / Q000737:chemistry
C042630:1-chloro-2,4-dinitrobenzene-glutathione conjugate; D000097:Acetonitriles; D004137:Dinitrochlorobenzene; D008041:Linoleic Acids; D008042:Linolenic Acids; D008054:Lipid Peroxides; C038649:13-hydroperoxy-9,11-octadecadienoic acid; C064441:13-oxo-9,11-octadecadienoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D019787:Linoleic Acid; D009195:Peroxidase; D005978:Glutathione; D010100:Oxygen; C032159:acetonitrile