Different selectivities of oxidants during oxidation of methionine residues in the α‐1‐proteinase inhibitor

Oxidation of the reactive site methionine (Met) in α‐1‐proteinase inhibitor (α‐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 α‐1‐PI, we measured the molar ratio Met(O)/α‐1‐PI at total inactivation. This ratio was determined to be 1.2 for both the myeloperoxidase/H 2 O 2 /chloride system and the related compound NH 2 Cl. With taurine monochloramine, another myeloperoxidase‐related oxidant, 1.05 mol Met(O) were generated per mol α‐1‐PI during inactivation. These oxidants attack preferentially one Met residue in α‐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 reactive site Met in α‐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 α‐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 α‐1‐PI activity in vivo.