title: Differential effects of oxidizing agents on human plasma alpha 1-proteinase inhibitor and human neutrophil myeloperoxidase.
abstract: Human alpha 1-proteinase inhibitor is easily susceptible to inactivation because of the presence of a methionyl residue at its reactive site. Thus, oxidizing species derived from the myeloperoxidase system (enzyme, H2O2, and C1-), as well as hypochlorous acid, can inactivate this inhibitor, although H2O2 alone has no effect. Butylated hydroxytoluene, a radical scavenger, partially protects alpha 1-proteinase inhibitor from the myeloperoxidase system and completely protects it from hypochlorous acid. Each oxidant also reacts differently with the inhibitor, in that the myeloperoxidase system and hypochlorous acid can each oxidize as many as six methionyl residues, but hypochlorous acid can also oxidize a single tyrosine residue. Myeloperoxidase can be inactivated by hypochlorous acid, by autoxidation in the presence of H2O2 and C1-, as well as by H2O2 alone. Butylated hydroxytoluene completely protects this enzyme from hypochlorous acid inactivation, does not affect the action of H2O2, and enhances autoinactivation. As many as six methionyl residues and two tyrosine residues could be oxidized during autoxidation and six methionine residues by H2O2 alone. Eight methionine residues and one tyrosine residue could be oxidized by hypochlorous acid. The tyrosine residue in myeloperoxidase was oxidized only at a relatively high concentration (600 microM) of hypochlorous acid at which point the enzyme simultaneously and completely lost its enzymatic activity. Loss of activity of myeloperoxidase could also be correlated with the loss of the heme groups present in the enzyme when a relatively high concentration of hypochlorous acid (600 microM) was used and also during autoxidation. It appears that once there is sufficient oxidant to modify one of the tyrosine residues, the heme group itself becomes susceptible.
authors.forename: N R
authors.initials: NR
authors.lastname: Matheson
authors.forename: J
authors.initials: J
authors.lastname: Travis
mesh_terms: D000596:Amino Acids / Q000032:analysis; D001798:Blood Proteins / Q000378:metabolism*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D007700:Kinetics; D009504:Neutrophils / Q000201:enzymology*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000097:blood*; D010544:Peroxidases / Q000097:blood*; D013053:Spectrophotometry; D000515:alpha 1-Antitrypsin
chemical_list: D000596:Amino Acids; D001798:Blood Proteins; D000515:alpha 1-Antitrypsin; D002084:Butylated Hydroxytoluene; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D010544:Peroxidases; D009195:Peroxidase