Kinetics of the reaction between human C1-esterase inhibitor and C1r or C1s.

Abstract

The kinetics of the reactions of C‐esterase inhibitor with Cs or Cr has been studied in purified systems. Both reactions were found to proceed in two steps: a fast reversible second‐order reaction followed by a slower irreversible first‐order transition according to the following scheme: . The rate constant k1 for the reaction between Cs and C‐esterase inhibitor was found to be 1.4 × 105 M−1 s−1 at 25°C and 4.7 × 105 M−1 s−1 at 37°C, while the corresponding values for the reaction between Cr and C‐esterase inhibitor were 2.5 × 103 M−1 s−1 and 4.4 × 104 M−1 s−1, respectively. The dissociation constant K of the initial complex was estimated as 1–2 nM for the complex with Cs and 20–50 nM for the complex with Cr. Heparin was found to accelerate the rate of the Cs/C‐esterase inhibitor reaction by a 16‐fold increase in k1 at heparin concentrations above 100 mg/l, whereas no effect was obtained on the thermodynamic equilibrium. The inhibition of purified Cs added to dilutions of plasma or serum was found to proceed as expected from their known concentrations of C‐esterase inhibitor and the rate constants determined in the purified system. Thus, the half‐life of Cs in plasma under pseudo‐first‐order kinetics would be about 1 s