Myoglobin-catalyzed hydrogen peroxide dependent arachidonic acid peroxidation.
Hemeproteins promote lipid hydroperoxide-dependent lipid peroxidation in vitro. Only recently have studies demonstrated that certain hemeproteins peroxidize lipids in a lipid-hydroperoxide-independent manner. To understand fully the interaction between reactive oxygen metabolites, myoglobin and lipid, we investigate the possibility that myoglobin may use xanthine oxidase-generated superoxide and/or hydrogen peroxide to catalyze peroxidation of a polyunsaturated fatty acid. Our studies demonstrate that myoglobin, in the presence of hypoxanthine and xanthine oxidase, catalyze the peroxidation of arachidonic acid. Oxy (ferrous) myoglobin appears to be the most effective catalyst for arachidonic acid peroxidation when compared to metmyglobin, hemoglobin, or ADP-iron chelates. Inhibition studies reveal that myoglobin uses hydrogen peroxide, not superoxide to form either an oxo-heme-oxidant or caged radical that initiates arachidonate peroxidation. The reactivity of this oxidant is similar to that of ferryl iron or hydroxyl free radical. Our results suggest that this reaction may be important in myocardial reperfusion injury since reoxygenation of ischemic myocardium results in a burst of xanthine oxidase-generated superoxide and hydrogen peroxide in proximity to cellular myoglobin.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology; D002384:Catalysis; D004285:Dogs; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006420:Hemeproteins / Q000494:pharmacology; D006736:Horses; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D008315:Malondialdehyde / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009211:Myoglobin / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism; D014907:Whales; D014969:Xanthine Oxidase / Q000494:pharmacology
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D006420:Hemeproteins; D007042:Hypoxanthines; D009211:Myoglobin; D016718:Arachidonic Acid; D019271:Hypoxanthine; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D014969:Xanthine Oxidase; D010100:Oxygen