Turnover of *I-protein C inhibitor and *I-alpha 1-antitrypsin and their complexes with activated protein C.
The rates of clearance and catabolism of human protein C inhibitor (PCI) and human alpha 1-antitrypsin (alpha 1-AT) and their complexes with human activated protein C (APC) were studied in the rabbit. The radioiodinated-free inhibitors had biologic half-lives of 23.4 and 62.1 hours, respectively, while the corresponding *I-labeled activated-protein C complexes were cleared with half-lives of 19.6 +/- 3.1 and 72.2 +/- 6.1 minutes. Complex clearances were linked to their catabolism as shown by a correlation between clearance and the appearance of free radioiodine in the plasma. Thus, the difference in the rates of catabolism would result in a fivefold greater amount of alpha 1-AT-APC complex than PCI-APC complex 1 hour after the formation of equal amounts of these in vivo. These results lead to the conclusion that the relative contribution of PCI and alpha 1-AT to the physiologic inhibition of APC cannot be determined only from the rates of the formation of these complexes in vitro, or from measurement of their levels in plasma. The APC-PCI complex is unstable as compared with the APC-alpha 1-AT complex, compounding the problem of estimating rates of complex formation from their levels in plasma.
Laurell
M
M
Department of Clinical Chemistry, Malmö General Hospital, Sweden.
Stenflo
J
J
Carlson
T H
TH
D000818:Animals; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics*; D002852:Chromatography, Ion Exchange; D006207:Half-Life; D006801:Humans; D007163:Immunosorbent Techniques; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D011486:Protein C / Q000378:metabolism / Q000493:pharmacokinetics*; D018046:Protein C Inhibitor; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000493:pharmacokinetics*; D000515:alpha 1-Antitrypsin / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics*
D001798:Blood Proteins; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D011486:Protein C; D018046:Protein C Inhibitor; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin