Different selectivities of oxidants during oxidation of methionine residues in the alpha-1-proteinase inhibitor.
Oxidation of the reactive site methionine (Met) in alpha-1-proteinase inhibitor (alpha-1-PI) to methionine sulfoxide (Met(O] is known to cause depletion of its elastase inhibitory activity. To estimate the selectivity of different oxidants in converting Met to Met(O) in alpha-1-PI, we measured the molar ratio Met(O)/alpha-1-PI at total inactivation. This ratio was determined to be 1.2 for both the myeloperoxidase/H2O2/chloride system and the related compound NH2Cl. With taurine monochloramine, another myeloperoxidase-related oxidant, 1.05 mol Met(O) were generated per mol alpha-1-PI during inactivation. These oxidants attack preferentially one Met residue in alpha-1-PI, which is identical with Met 358, as concluded from the parallelism of loss of elastase inhibitory activity and oxidation of Met. A similar high specificity for Met oxidation was determined for the xanthine oxidase-derived oxidants. In contrast, the ratio found for ozone and m-chloroperoxybenzoic acid was 6.0 and 5.0, respectively, indicating oxidation of additional Met residues besides the relative site Met in alpha-1-PI, i.e. unselective action of these oxidants. Further studies were performed on the efficiency of oxidants for total depletion of the elastase inhibitory capacity of alpha-1-PI. Ozone and m-chloroperoxybenzoic acid were 10-fold less effective and the superoxide anion/hydroxyl radicals were 30-50-fold less effective to inactivate the elastase inhibitory activity as compared to the myeloperoxidase-derived oxidants. The myeloperoxidase-related oxidants are discussed as important regulators of alpha-1-PI activity in vivo.
Maier
K L
KL
GSF-Projekt Inhalation, Arbeitsgruppe Biochemie, Neuherberg, FRG.
Matejkova
E
E
Hinze
H
H
Leuschel
L
L
Weber
H
H
Beck-Speier
I
I
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D002723:Chlorobenzoates / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology; D010084:Oxidation-Reduction; D010126:Ozone / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D009195:Peroxidase / Q000378:metabolism; D013552:Swine; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D002712:Chlorides; D002723:Chlorobenzoates; D000515:alpha 1-Antitrypsin; D013654:Taurine; C043410:N-chlorotaurine; D010126:Ozone; D008715:Methionine; D006861:Hydrogen Peroxide; D009195:Peroxidase; D014969:Xanthine Oxidase; D010196:Pancreatic Elastase; C000433:3-chloroperbenzoic acid