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Platelet phenol sulfotransferase and erythrocyte catechol‐ O ‐methytransferase activities: Correlation with methyldopa metabolism
Author(s) -
Campbell N R C,
Dunnette J H,
Mwaluko G,
Van Loon J,
Weinshilboum R M
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.9
Subject(s) - chemistry , methyldopa , metabolite , metabolism , hippuric acid , urine , platelet , mephenytoin , enzyme , pharmacology , thermolabile , biochemistry , sulfotransferase , endocrinology , medicine , blood pressure , cytochrome p450 , cyp2c19
Methyldopa is metabolized by sulfate conjugation catalyzed by phenol sulfotransferase (PST), O‐methylation catalyzed by catechol‐O‐methyltransferase (COMT), and decarboxylation catalyzed by aromatic L‐amino acid decarboxylase. These experiments were performed to determine whether individual variations in red blood cell (RBC) COMT and platelet PST activities might reflect variations in the metabolism of methyldopa in man. Methyldopa, 3.5 mg/kg, was taken orally by 28 subjects. Blood samples were obtained from these subjects for the assay of platelet PST and RBC COMT activities, and a 24‐hr urine sample was collected for the measurement of methyldopa and its major metabolites. Human platelets contain two independently regulated forms of PST. One form is thermolabile (TL), and the other is thermostable (TS). Methyldopa and α‐methyldopamine are substrates for the TL but not for the TS form of PST. The results of the experiment showed significant correlations between TL platelet PST activity and the proportion of α‐methyldopamine excreted as a sulfate conjugate, and between RBC COMT activity and the proportion of methyldopa excreted as an O‐methyl metabolite. There was no significant correlation, however, between TL platelet PST activity, and the proportion of methyldopa itself excreted as a sulfate conjugate. These results are compatible with the conclusion that differences among subjects in drug metabolizing enzyme activities are one factor responsible for wide individual variations in methyldopa metabolism in man. Clinical Pharmacology and Therapeutics (1984) 35, 55–63; doi: 10.1038/clpt.1984.9