Fa Z, Dryhurst G
Department of Chemistry and Biochemistry, University of Oklahoma, Norman 73019-0370.
Biochem Pharmacol. 1991 Nov 6;42(11):2209-19. doi: 10.1016/0006-2952(91)90358-c.
Tyrosinase (EC 1.14.18.1)/O2, ceruloplasmin (human type X)/O2, and peroxidase (EC 1.11.1.7)/H2O2 oxidized the endogenous central nervous system alkaloid salsolinol (SAL) at physiological pH. The proximate oxidation product was an electrophilic ortho-quinone (4) which at pH 7.0 rapidly tautomerized. Four major initial products were formed from 4: cis- and trans-1,2,3,4-tetrahydro-1-methyl-4,6,7-isoquinolinetriol (A and B, respectively), 2,3,4-trihydro-1-methyl-7-hydroxy-6-oxyisoquinoline (C), and 1-methyl-6,7-isoquinoline diol (D). Mechanisms describing the formation of these products have been presented. Ortho-quinone 4, formed in the enzyme-mediated reactions, was rapidly attacked by glutathione to yield the 5-S-, 8-S-, and 5,8-bi-S-glutathionyl conjugates of SAL. Preliminary experiments indicated that injection of A, B and C into the CNS of mice evoked profound behavioral effects. Quinone methide C was toxic. The potential role of the oxidation of salsolinol in the neurodegenerative and behavioral effects associated with chronic alcoholism is discussed.
酪氨酸酶（EC 1.14.18.1）/O₂、铜蓝蛋白（人类X型）/O₂以及过氧化物酶（EC 1.11.1.7）/H₂O₂在生理pH值下可氧化内源性中枢神经系统生物碱四氢异喹啉醇（SAL）。其直接氧化产物是一种亲电性邻醌（4），该邻醌在pH 7.0时会迅速发生互变异构。4会生成四种主要的初始产物：顺式和反式1,2,3,4-四氢-1-甲基-4,6,7-异喹啉三醇（分别为A和B）、2,3,4-三氢-1-甲基-7-羟基-6-氧代异喹啉（C）以及1-甲基-6,7-异喹啉二醇（D）。文中已阐述了描述这些产物形成过程的机制。在酶介导反应中形成的邻醌4会迅速被谷胱甘肽攻击，生成SAL的5-S-、8-S-以及5,8-双-S-谷胱甘肽共轭物。初步实验表明，将A、B和C注射到小鼠中枢神经系统中会引发显著的行为效应。亚甲基醌C具有毒性。文中讨论了四氢异喹啉醇氧化在与慢性酒精中毒相关的神经退行性变和行为效应中的潜在作用。
