Zimatkin S M, Deitrich R A
Institute of Biochemistry, Academy of Sciences of Belarus, Grodno, BelarusAlcohol Research Center, University of Colorado Health Science Center, Denver, Colorado, USA.
Addict Biol. 1997 Oct;2(4):387-400. doi: 10.1080/13556219772444.
Acetaldehyde is suspected of being involved in the central mechanism of central nervous system depression and addiction to ethanol, but in contrast to ethanol, it can not penetrate easily from blood into the brain because of metabolic barriers. Therefore, the possibility of ethanol metabolism and acetaldehyde formation inside the brain has been one of the crucial questions in biomedical research of alcoholism. This article reviews the recent progress in this area and summarizes the evidence on the first stage of ethanol oxidation in the brain and the specific enzyme systems involved. The brain alcohol dehydrogenase and microsomal ethanol oxidizing systems, including cytochrome P450 II E1 and catalase are considered. Their physicochemical properties, the isoform composition, substrate specificity, the regional and subcellular distribution in CNS structures, their contribution to brain ethanol metabolism, induction under ethanol administration and the role in the neurochemical mechanisms of psychopharmacological and neurotoxic effects of ethanol are discussed. In addition, the nonoxidative pathway of ethanol metabolism with the formation of fatty acid ethyl esters and phosphatidylethanol in the brain is described.
乙醛被怀疑参与中枢神经系统抑制和乙醇成瘾的核心机制，但与乙醇不同的是，由于代谢障碍，它难以从血液轻易进入大脑。因此，大脑内乙醇代谢和乙醛形成的可能性一直是酒精中毒生物医学研究中的关键问题之一。本文综述了该领域的最新进展，并总结了大脑中乙醇氧化第一阶段及相关特定酶系统的证据。文中考虑了大脑乙醇脱氢酶和微粒体乙醇氧化系统，包括细胞色素P450 II E1和过氧化氢酶。讨论了它们的物理化学性质、同工型组成、底物特异性、在中枢神经系统结构中的区域和亚细胞分布、对大脑乙醇代谢的贡献、乙醇给药后的诱导作用以及在乙醇心理药理学和神经毒性作用的神经化学机制中的作用。此外，还描述了大脑中乙醇代谢形成脂肪酸乙酯和磷脂酰乙醇的非氧化途径。
