[Kinetics of beta-lactamase inhibition by clavulanic acid].
The mechanisms of action of 3 R-factors on beta-lactamases (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6) (TEM-1 pI = 5.4, TEM-2 pI = 5.6 and Pitton's type 2 pI = 7.7) have been kinetically analyzed for clavulanic acid inactivation. Clavulanic acid appears as a competitive and irreversible inhibitor (Kcat inhibitor) reacting in two steps: a, formation of a reversible enzyme . inhibitor complex (characterized by a Ki); b, evolution of the reversible complex into a new derivative (covalent, stable and inactive) by monomolecular kinetics characterized by a k6 (or Kcat) related to half-life. The kinetic constants are: TEM-1: Ki = 0.8 micrometer, k6 = 0.027 s-1; TEM-2: Ki = 0.7 micrometer, k6 = 0.03 s-1; type 2: Ki = 0.6 micrometer, k6 = 0.046 s-1. These results justify the 'progressive irreversible' character of the inhibition generally described.
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D008956:Models, Chemical; D010400:Penicillin G / Q000378:metabolism; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases; D010400:Penicillin G
Cinetique de l'inhibition de beta-lactamases par l'acide clavulanique.