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人碳酸酐酶II催化的二氧化碳水合反应的阴离子抑制作用。机理探讨。

Anion inhibition of CO2 hydration catalyzed by human carbonic anhydrase II. Mechanistic implications.

作者信息

Tibell L, Forsman C, Simonsson I, Lindskog S

出版信息

Biochim Biophys Acta. 1984 Sep 25;789(3):302-10. doi: 10.1016/0167-4838(84)90186-9.

DOI:10.1016/0167-4838(84)90186-9
PMID:6433979
Abstract

Five monovalent anions, I-, N3-, SCN-, NCO- and Au(CN)2-, were investigated as inhibitors of CO2 hydration catalyzed by human carbonic anhydrase II (carbonate hydro-lyase, EC 4.2.1.1). Predominantly uncompetitive inhibition patterns were observed at pH near 9 in all cases. While Dixon plots of Km/V vs. inhibitor concentration were linear, all the investigated anions except NCO- gave nonlinear Dixon plots of 1/V vs. inhibitor concentration. The anion SCN- was also tested at pH 7.4 and 6.4. Essentially noncompetitive patterns of inhibition of CO2 hydration were obtained at both these pH values. These results are analyzed in terms of two rivaling mechanism models, a kinetic scheme originally proposed by Steiner et al. (Steiner, H., Jonsson, B.-H. and Lindskog, S. (1975) Eur. J. Biochem. 59, 253-259) and a rapid-equilibrium kinetic scheme proposed by Pocker and Deits (Pocker, Y. and Deits, T.L. (1982) J. Am. Chem. Soc. 104, 2424-2434). It is concluded that the observed steady-state inhibition patterns are compatible with both models, but that discriminatory data, strongly favouring the model of Steiner et al., are available in the literature.

摘要

研究了5种单价阴离子I⁻、N₃⁻、SCN⁻、NCO⁻和Au(CN)₂⁻作为人碳酸酐酶II(碳酸水解酶,EC 4.2.1.1)催化CO₂水合反应抑制剂的情况。在接近pH 9的条件下,所有情况均观察到主要为非竞争性抑制模式。虽然Km/V对抑制剂浓度的Dixon图呈线性,但除NCO⁻外,所有研究的阴离子的1/V对抑制剂浓度的Dixon图均呈非线性。还在pH 7.4和6.4条件下测试了阴离子SCN⁻。在这两个pH值下均获得了对CO₂水合反应的基本非竞争性抑制模式。根据两种相互竞争的机制模型对这些结果进行了分析,一种是Steiner等人最初提出的动力学方案(Steiner, H., Jonsson, B.-H.和Lindskog, S. (1975) Eur. J. Biochem. 59, 253 - 259),另一种是Pocker和Deits提出的快速平衡动力学方案(Pocker, Y.和Deits, T.L. (1982) J. Am. Chem. Soc. 104, 2424 - 2434)。得出的结论是,观察到的稳态抑制模式与两种模型均相符,但文献中有明显支持Steiner等人模型的鉴别性数据。

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