Harris R Adron, Trudell James R, Mihic S John
Section of Neurobiology and Waggoner Center for Alcohol and Addiction Research, Institutes for Neuroscience and Cell & Molecular Biology, University of Texas, Austin, TX 78712, USA.
Sci Signal. 2008 Jul 15;1(28):re7. doi: 10.1126/scisignal.128re7.
Ethanol produces a wide variety of behavioral and physiological effects in the body, but exactly how it acts to produce these effects is still poorly understood. Although ethanol was long believed to act nonspecifically through the disordering of lipids in cell membranes, proteins are at the core of most current theories of its mechanisms of action. Although ethanol affects various biochemical processes such as neurotransmitter release, enzyme function, and ion channel kinetics, we are only beginning to understand the specific molecular sites to which ethanol molecules bind to produce these myriad effects. For most effects of ethanol characterized thus far, it is unknown whether the protein whose function is being studied actually binds ethanol, or if alcohol is instead binding to another protein that then indirectly affects the functioning of the protein being studied. In this Review, we describe criteria that should be considered when identifying alcohol binding sites and highlight a number of proteins for which there exists considerable molecular-level evidence for distinct ethanol binding sites.
乙醇在体内会产生各种各样的行为和生理效应，但人们对其产生这些效应的具体作用方式仍知之甚少。尽管长期以来人们认为乙醇是通过扰乱细胞膜中的脂质来非特异性地发挥作用，但在目前关于其作用机制的大多数理论中，蛋白质才是核心。虽然乙醇会影响各种生化过程，如神经递质释放、酶功能和离子通道动力学，但我们才刚刚开始了解乙醇分子结合产生这些众多效应的具体分子位点。就目前已明确的乙醇的大多数效应而言，尚不清楚所研究功能的蛋白质是否真的能结合乙醇，还是酒精是与另一种蛋白质结合，进而间接影响所研究蛋白质的功能。在本综述中，我们描述了在识别酒精结合位点时应考虑的标准，并重点介绍了一些在分子水平上有大量证据表明存在不同乙醇结合位点的蛋白质。
