Concerted actions of the catechol O-methyltransferase and the cytosolic sulfotransferase SULT1A3 in the metabolism of catecholic drugs
作者： Katsuhisa Kurogi , Adnan Alazizi , Ming-Yih Liu , Yoichi Sakakibara , Masahito Suiko
DOI: 10.1016/J.BCP.2012.08.009
关键词:
摘要: Catecholic drugs had been reported to be metabolized through conjugation reactions, particularly methylation and sulfation. Whether how these two Phase II reactions may occur in a concerted manner, however, remained unclear. The current study was designed investigate the and/or sulfation of five catecholic drugs. Analysis spent media HepG2 cells metabolically labeled with [35S]sulfate presence individual revealed [35S]sulfated metabolites for dopamine, epinephrine, isoproterenol, isoetharine, but only one metabolite apomorphine. Further analyses using tropolone, catechol O-methyltransferase (COMT) inhibitor, indicated that isoetharine doubly conjugated (methylated sulfated) product, since its level decreased proportionately increasing concentrations tropolone added labeling media. Moreover, while inhibition resulted decrease total amount metabolites, appeared capable compensating suppressed metabolism four A two-stage enzymatic assay showed sequential mediated by, respectively, COMT cytosolic sulfotransferase SULT1A3. Collectively, results from present implied actions SULT1A3
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