Myeloperoxidase-catalyzed oxidation of tyrosine.
The oxidation of tyr by myleoperoxidase (MPO) is postulated to play a role in atherosclerotic plaque formation. MPO has been localized in plaques and a product of MPO-catalyzed oxidation of tyr, dityrosine, also found in plaques, is proposed to be a protein cross-linking agent. We have performed kinetic studies on the oxidation of tyr by MPO and investigated the role of substrate size on its oxidation. The kinetics of MPO-catalyzed oxidation of tyr where the tyr is free tyr, the dipeptides, tripeptides, and polypeptides were studied by stopped-flow methods. The rate of reaction with enzyme intermediates compound I and compound II are decreased with increasing substrate size. The amount of dityrosine formed was also decreased with increasing substrate size. The ability of sulfhydryl compounds to inhibit MPO-dependent dityrosine formation was investigated with reduced glutathione, cys, and met. Glutathione and cys both served as substrates for MPO compound I but not compound II, whereas met was not a substrate for either compound I or II. Met, an amino acid postulated to act as a "last chance" antioxidant for proteins, was not able to inhibit dityrosine formation from MPO-catalyzed oxidation of tyr. Glutathione and cys caused partial inhibition; however, it is possible that this inhibition was due to their ability to react directly with MPO rather than trapping the tyr radicals.
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Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, 16802, USA. mxt3@psu.edu
D000818:Animals; D002417:Cattle; D003432:Cross-Linking Reagents / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D007700:Kinetics; D008715:Methionine / Q000494:pharmacology; D008970:Molecular Weight; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D003432:Cross-Linking Reagents; D005609:Free Radicals; D016877:Oxidants; D010455:Peptides; D013439:Sulfhydryl Reagents; D014443:Tyrosine; D008715:Methionine; C007543:dityrosine; D009195:Peroxidase; D005978:Glutathione; D003545:Cysteine