Haworth R A, Hunter D R
J Membr Biol. 1980 Jun 15;54(3):231-6. doi: 10.1007/BF01870239.
The control by nucleotides of the Ca2+ -activated channel which regulates the nonspecific permeability of the mitochondrial inner membrane has been investigated quantitatively. The cooperative binding of two molecules of ADP to the internal (matrix) side of the channel causes a mixed-type inhibition of channel activity. ATP, AMP, cAMP and GDP are all ineffective. NADH shows a pattern of inhibition similar to that of ADP, though the apparent KI is higher by a factor of 200. NADPH relieves the inhibition by NADH. NAD+ also inhibits, b,t its affinity is a factor of 10 less than that of NADH. When ADP and NADH are added together, they act synergistically to inhibit the Ca2+-activated channel. It is concluded that the concept of the modification of enzyme activity by the allosteric binding of nucleotides, which is well established for soluble enzyme systems, also has application to the regulation of channels that control membrane permeability.
已经对核苷酸对调节线粒体内膜非特异性通透性的Ca2+激活通道的控制进行了定量研究。两分子ADP协同结合到通道的内侧（基质侧）会导致通道活性的混合型抑制。ATP、AMP、cAMP和GDP均无作用。NADH表现出与ADP相似的抑制模式，尽管其表观抑制常数（KI）高出200倍。NADPH可解除NADH的抑制作用。NAD+也有抑制作用，但其亲和力比NADH低10倍。当ADP和NADH一起添加时，它们协同作用抑制Ca2+激活通道。得出的结论是，核苷酸变构结合修饰酶活性的概念在可溶性酶系统中已得到充分确立，也适用于控制膜通透性的通道的调节。
