In vivo catabolism of alpha 1-antichymotrypsin is mediated by the Serpin receptor which binds alpha 1-proteinase inhibitor, antithrombin III and heparin cofactor II.
The in vivo catabolism of 125I-labeled alpha 1-antichymotrypsin was studied in our previously described mouse model. Native alpha 1-antichymotrypsin cleared with an apparent t1/2 of 85 min, but alpha 1-antichymotrypsin in complex with chymotrypsin or cathepsin G cleared with a t1/2 of 12 min. Clearance of the complex was blocked by a large molar excess of unlabeled complexes of proteinases with either alpha 1-antichymotrypsin or alpha 1-proteinase inhibitor. These studies indicate that the clearance of alpha 1-antichymotrypsin-proteinase complexes utilizes the same pathway as complexes with the homologous inhibitor alpha 1-proteinase inhibitor. Previous studies have demonstrated that this pathway is also responsible for the catabolism of two other serine proteinase inhibitors, antithrombin III and heparin cofactor II. This pathway is thus responsible for removing several proteinases involved in coagulation and inflammation from the circulation, thereby decreasing the likelihood of adventitious proteolysis.
Pizzo
S V
SV
Department of Pathology, Duke University Medical Center, Durham, NC.
Mast
A E
AE
Feldman
S R
SR
Salvesen
G
G
D000990:Antithrombin III / Q000378:metabolism* / Q000493:pharmacokinetics; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism* / Q000493:pharmacokinetics; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000378:metabolism* / Q000493:pharmacokinetics; D006207:Half-Life; D015844:Heparin Cofactor II; D006801:Humans; D011480:Protease Inhibitors / Q000378:metabolism*; D012697:Serine Endopeptidases; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism* / Q000493:pharmacokinetics; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D006023:Glycoproteins; D011480:Protease Inhibitors; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; D015844:Heparin Cofactor II; D000990:Antithrombin III; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534096:Ctsg protein, mouse