title: Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin.
abstract: The association rate constants for the interaction of alpha-1-proteinase inhibitor, oxidized alpha-1-proteinase inhibitor, and alpha-1-antichymotrypsin with several mammalian serine proteinases have been determined. The results indicate that leukocyte elastase reacts more rapidly with alpha-1-proteinase inhibitor than any other proteinase tested, while leukocyte cathepsin G shows the strongest association with alpha-1-antichymotrypsin. Oxidation of the critical methionine residue of alpha-1-proteinase inhibitor reduces the association with leukocyte elastase by a factor of more than 2000 and also lowers the association with all of the other enzymes tested with the exception of chymotrypsin. Significantly, oxidation completely abolishes any interaction of alpha-1-proteinase inhibitor with porcine elastase, human plasmin or human thrombin. These data support previous results (Johnson, D., and Travis, J. (1979) J. Biol. Chem. 254, 4022-4026) which indicated that oxidation of human alpha-1-proteinase inhibitor in vivo could reduce the effectiveness of this inhibitor in controlling proteolysis. In the lung, in particular, oxidizing agents of both chemical and biological sources could, indirectly, augment elastolysis in this tissue, resulting in the development of pulmonary emphysema.
mesh_terms: D000818:Animals; D002918:Chymotrypsin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D010084:Oxidation-Reduction; D011485:Protein Binding; D012697:Serine Endopeptidases; D014361:Trypsin Inhibitors / Q000494:pharmacology; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
chemical_list: D014361:Trypsin Inhibitors; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; D010450:Endopeptidases; D012697:Serine Endopeptidases; D002918:Chymotrypsin