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锌离子对促成500 kDa硫酸葡聚糖依赖性因子XII(哈格曼因子)激活的动力学事件的影响。

Influence of Zn2+ on the kinetic events that contribute to the 500-kDa dextran-sulfate-dependent activation of factor XII (Hageman factor).

作者信息

Loiseau C, Randriamahazaka H N, Nigretto J M

机构信息

Université de Cergy Pontoise, Laboratoire d'Electrochimie et des Matériaux Appliqués, Neuville/Oise, Cergy Pontoise, France.

出版信息

Eur J Biochem. 1997 May 15;246(1):204-10. doi: 10.1111/j.1432-1033.1997.00204.x.

DOI:10.1111/j.1432-1033.1997.00204.x
PMID:9210485
Abstract

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.

摘要

研究了锌离子对在500 kDa硫酸葡聚糖存在下可能有助于人凝血因子XII激活及随后自身激活的动力学和平衡步骤的影响。为分析结果,使用了根据先前研究中提出的模型确定的总体自身激活常数的表达式。对在不同锌水平下获得的动力学进行比较,其中包括低于孵育混合物中NaCl引入的残留浓度的量,结果表明,添加高达5 microM的Zn2+可使因子XII与表面结合的可用位点平均数从220降至172,并使因子XII的一级激活速率提高一个数量级,在存在550 nM硫酸葡聚糖的情况下,从(1.6±0.4)×10(-4) s(-1)提高到(8.0±0.4)×10(-4) s(-1)。锌的存在对因子XII/表面解离常数(1 microM)、表观催化常数或与假定的多阶段动力学序列相关的表观米氏常数均无影响。使用该模型可以成功解释锌存在引起的大多数实验趋势,从而增强了其在不同条件下的可靠性。

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