Abstract
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 theportion of methyldopa itself excreted as a sulfate conjugate. These results are compatible with wit conclusion that differences among subjects in drug metabolizing enzyme activities are one factor responsible for wide individual variations in methyldopa metabolism in man.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 55-63 |
| Number of pages | 9 |
| Journal | Clinical Pharmacology and Therapeutics |
| Volume | 35 |
| Issue number | 1 |
| State | Published - Jan 1984 |
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ASJC Scopus subject areas
- Pharmacology
Cite this
Platelet phenol sulfotransferase and erythrocyte catechol-O-methyltransferase activities : Correlation with methyldopa metabolism. / Campbell, N. R C; Dunnette, J. H.; Mwaluko, G.; Van Loon, J.; Weinshilboum, Richard M.
In: Clinical Pharmacology and Therapeutics, Vol. 35, No. 1, 01.1984, p. 55-63.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Platelet phenol sulfotransferase and erythrocyte catechol-O-methyltransferase activities
T2 - Correlation with methyldopa metabolism
AU - Campbell, N. R C
AU - Dunnette, J. H.
AU - Mwaluko, G.
AU - Van Loon, J.
AU - Weinshilboum, Richard M
PY - 1984/1
Y1 - 1984/1
N2 - 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 theportion of methyldopa itself excreted as a sulfate conjugate. These results are compatible with wit conclusion that differences among subjects in drug metabolizing enzyme activities are one factor responsible for wide individual variations in methyldopa metabolism in man.
AB - 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 theportion of methyldopa itself excreted as a sulfate conjugate. These results are compatible with wit conclusion that differences among subjects in drug metabolizing enzyme activities are one factor responsible for wide individual variations in methyldopa metabolism in man.
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M3 - Article
VL - 35
SP - 55
EP - 63
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 1
ER -