亚砷酸盐和镉对腺苷酸环化酶的抑制作用：对相邻二硫醇需求的证据。

Inhibition of adenylate cyclase by arsenite and cadmium: evidence for a vicinal dithiol requirement.

作者信息

Spiegel A M, Brown E M, Aurbach G D

出版信息

J Cyclic Nucleotide Res. 1976 Nov-Dec;2(6):393-404.

Abstract

The effect of sodium arsenite and cadmium chloride on adenylate cyclase activity was examined in turkey erythrocyte membranes. Sodium arsenite was a weak inhibitor of adenylate cyclase -7mM produced only 60% inhibition. Its effect, however, was greatly potentiated by equimolar 2,3 dimercaprol- wherein 0.7 mM sodium arsenite inhibited 100% with an apparent Ki of 0.1 mM. Equimolar mercaptoethanol was less effective in potentiating sodium arsenite inhibition. Thus 0.7mM sodium arsenite in the presence of equimolar mercaptoethanol inhibited adenylate cyclase 56%. Excess 2,3 dimercaprol reversed inhibition by sodium arsenite or cadmium chloride. Sodium arsenite or cadmium chloride inhibited all forms of adenylate cyclase activity tested, including nonhormonal stimulation. Equimolar sodium arsenite and dimercaprol, at concentrations that caused 100% inhibition of adenylate cyclase activity, reduced the binding of the beta-receptor specific ligand iodohydroxybenzylpindolol by less than 15%. These results suggest that turkey erythrocyte membranes contain closely juxtaposed thiol groups and that interaction of such groups with arsenate interferes with the catalytic function of adenulate cyclase.

摘要

研究了亚砷酸钠和氯化镉对火鸡红细胞膜腺苷酸环化酶活性的影响。亚砷酸钠是腺苷酸环化酶的弱抑制剂——7mM时仅产生60%的抑制作用。然而，等摩尔的2,3-二巯基丙醇能大大增强其作用——其中0.7mM亚砷酸钠能100%抑制，表观抑制常数Ki为0.1mM。等摩尔的巯基乙醇增强亚砷酸钠抑制作用的效果较差。因此，在等摩尔巯基乙醇存在下，0.7mM亚砷酸钠抑制腺苷酸环化酶56%。过量的2,3-二巯基丙醇可逆转亚砷酸钠或氯化镉的抑制作用。亚砷酸钠或氯化镉抑制所有测试形式的腺苷酸环化酶活性，包括非激素刺激。等摩尔的亚砷酸钠和二巯基丙醇在导致腺苷酸环化酶活性100%抑制的浓度下，使β受体特异性配体碘羟基苄基吲哚洛尔的结合减少不到15%。这些结果表明，火鸡红细胞膜含有紧密相邻的巯基，这些基团与砷酸盐的相互作用会干扰腺苷酸环化酶的催化功能。