Influence of Zn2+ on the kinetic events that contribute to the 500-kDa dextran-sulfate-dependent activation of factor XII (Hageman factor).
The effect of zinc ions on kinetic and equilibrium steps that may contribute to the activation and subsequent autoactivation of human blood coagulation factor XII in the presence of 500-kDa dextran sulfate was studied. To analyze the results, the expression of the overall autoactivation constant that had been established from the model presented in a previous study was used. Comparison of the kinetics obtained at different levels of zinc, which included amounts lower than the residual concentration introduced by NaCl in the incubation mixture, suggested that the addition of Zn2+ up to 5 microM lowered the mean number of sites available for the binding of factor XII to the surface from 220 to 172 and increased the rate of the first-order activation of factor XII by one order of magnitude, from (1.6 +/- 0.4) x 10(-4) s(-1) to (8.0 +/- 0.4) x 10(-4) s(-1) in the presence of 550 nM dextran sulfate. Neither the factor XII/surface dissociation constant (1 microM), the apparent catalytic constant, nor the apparent Michaelis-Menten constant associated with the postulated multi-stage kinetic sequence were affected by the presence of zinc. Most experimental trends induced by the presence of zinc could be successfully interpreted by using the model, thus reinforcing its reliability under different conditions.
Loiseau
C
C
Université de Cergy Pontoise, Laboratoire d'Electrochimie et des Matériaux Appliqués, Neuville/Oise, Cergy Pontoise, France.
Randriamahazaka
H N
HN
Nigretto
J M
JM
D001665:Binding Sites; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D016264:Dextran Sulfate / Q000494:pharmacology*; D004563:Electrochemistry; D005174:Factor XII / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000378:metabolism; D013499:Surface Properties; D015032:Zinc / Q000494:pharmacology*
D010455:Peptides; D005174:Factor XII; D016264:Dextran Sulfate; D015032:Zinc