铜离子对钠钾ATP酶抑制作用的动力学

Kinetics of Cu2+ inhibition of Na+/K(+)-ATPase.

作者信息

Li J, Lock R A, Klaren P H, Swarts H G, Schuurmans Stekhoven F M, Wendelaar Bonga S E, Flik G

机构信息

Department of Animal Physiology, Faculty of Science, Toernooiveld, Nijmegen, The Netherlands.

出版信息

Toxicol Lett. 1996 Sep;87(1):31-8. doi: 10.1016/0378-4274(96)03696-x.

DOI:10.1016/0378-4274(96)03696-x

PMID:8701442

Abstract

The interaction of Cu2+ with enzymatic activity of rabbit kidney Na+/K(+)-ATPase was studied in media with buffered, defined free Cu2+ levels. The IC50-values are 0.1 mumol/l for Na+/K(+)-ATPase and 1 mumol/l for K(+)-pNPPase. Dithiothreitol (DTT) reverses the inhibitory effect of Cu2+ in vitro. Cu2+ exerts non-competitive effects on the enzyme with respect to Na+, K+, ATP or pNPP, but has a mixed-type inhibitory effect with respect to Mg2+. It is concluded that the appreciation of the inhibitory effect of Cu2+ on this enzyme requires carefully composed assay media that include a buffer for Cu2+, and that the IC50-values calculated according to this model indicate that Cu2+ may be more toxic than previously anticipated.

摘要

在具有缓冲的、确定的游离铜离子水平的介质中，研究了铜离子与兔肾钠钾ATP酶的酶活性之间的相互作用。钠钾ATP酶的半数抑制浓度（IC50）值为0.1微摩尔/升，对硝基苯磷酸酯酶（K(+)-pNPPase）的IC50值为1微摩尔/升。二硫苏糖醇（DTT）在体外可逆转铜离子的抑制作用。铜离子对该酶的钠、钾、ATP或对硝基苯磷酸（pNPP）表现出非竞争性作用，但对镁离子具有混合型抑制作用。得出的结论是，要评估铜离子对该酶的抑制作用，需要精心配制的测定介质，其中包括用于铜离子的缓冲液，并且根据该模型计算出的IC50值表明，铜离子可能比之前预期的更具毒性。