The catabolism of intact, reactive centre-cleaved and proteinase-complexed C1 inhibitor in the guinea pig.
Clearance rates in the guinea pig were determined for intact guinea pig and human C1 inhibitor, the complexes of both inhibitors with human Cls, beta factor XIIa and kallikrein, and for each inhibitor cleaved at its reactive centre with trypsin. Intact human and guinea pig C1 inhibitor were cleared from the circulation more slowly (t1/2s of 9-7 h and 12.1 h and fractional catabolic rates (FCRs) of 0.09 and 0.117) than any of their cleaved or complexed forms. The reactive centre-cleaved inhibitors were cleared with half-lives of 6.75 h for humans and 10.1 h for the guinea pig. The complexes with target proteases were catabolized much more rapidly, with half-lives ranging from 3-08 h to 4.3 h. The complexes with kallikrein were cleared more slowly than those with Cls and beta factor XIIa. Complexes prepared with the guinea pig and human inhibitors were cleared at equivalent rates. The free inactivated proteases were cleared at rates similar to the equivalent complexes, except for kallikrein, which was cleared more rapidly than its complex. The fact that the complexes with different target proteases differed in their catabolism and that protease and complex catabolism were similar suggests that protease may play a direct role in clearance.
Malek
R
R
Division of Nephrology, Children's Hospital Research Foundation, Cincinnati, OH 45229-3039, USA.
Aulak
K S
KS
Davis
A E
AE
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003174:Complement C1 Inactivator Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics*; D003173:Complement C1s / Q000737:chemistry / Q000493:pharmacokinetics; D010450:Endopeptidases / Q000737:chemistry / Q000493:pharmacokinetics*; D015956:Factor XIIa / Q000737:chemistry / Q000493:pharmacokinetics; D006168:Guinea Pigs; D006801:Humans; D007610:Kallikreins / Q000737:chemistry / Q000493:pharmacokinetics; D008969:Molecular Sequence Data
D003174:Complement C1 Inactivator Proteins; D010450:Endopeptidases; D007610:Kallikreins; D015956:Factor XIIa; D003173:Complement C1s