Interactions of salsolinol with oxidative enzymes.
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.
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Department of Chemistry and Biochemistry, University of Oklahoma, Norman 73019-0370.
Dryhurst
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D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D002570:Ceruloplasmin / Q000378:metabolism*; D004563:Electrochemistry; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism*; D011809:Quinones
D007546:Isoquinolines; D011809:Quinones; C036617:salsolinol; D009195:Peroxidase; D014442:Monophenol Monooxygenase; D002570:Ceruloplasmin; D005978:Glutathione; D010100:Oxygen