α-Methyldopa, α-methyldopamine and α-methylnoradrenaline: Substrates for the thermolabile form of human platelet phenol sulphotransferase

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Abstract

Sulphate conjugation catalyzed by phenol sulphotransferase (PST) is an important pathway in the catabolism of α-methyldopa (MD). Variations in PST activity in an easily obtained tissue such as the human platelet might reflect individual differences in the sulphate conjugation of MD in other organs and tissues. There are at least two forms of human platelet PST, a thermolabile form for which dopamine is a substrate and a thermostable form for which low concentrations of phenol can serve as a substrate. MD, α-methyldopamine (MDA) and α-methylnoradrenaline (MNA) were tested as substrates for human platelet PST. All three were substrates for the thermolabile form of the enzyme and none were substrates for the thermostable form of PST. Apparent Michaelis-Menten (K(m)) values for MD, MDA and MNA were 5.5, 0.014 and 0.28 mM, respectively. Apparent K(m) values for 3'-phosphoadenosine-5'-phosphosulphate, the sulphate donor for the reaction, were 0.08, 0.13 and 0.10 μM, respectively, for the three catechol substrates. The pH optima for the reaction were 7.5 for MD and 6.5 for both MDA and MNA. When platelet homogenates from 20 individual subjects were tested, there were significant correlations between PST activities measured with dopamine and those measured with MD, MDA and MNA (r = 0.54, 0.98 and 0.93, P < 0.02, < 0.001, and < 0.001, respectively), but not between activities measured with low concentrations of phenol and those measured with MD, MDA and MNA (r = 0.021, 0.045 and 0.046, respectively). These results were also compatible with the conclusion that MD, MDA and MNA were substrates for the thermolabile form of platelet PST. These observations will make it possible to test the hypothesis that variations in the activity of the thermolabile form of platelet PST may reflect individual differences in the sulphate conjugation of MD, MDA and MNA.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalBritish Journal of Clinical Pharmacology
Volume14
Issue number2
StatePublished - 1982
Externally publishedYes

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Deoxyepinephrine
Arylsulfotransferase
Methyldopa
Blood Platelets
Sulfates
Phenol
Individuality
Dopamine
Phosphoadenosine Phosphosulfate

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

@article{707fc5e12d6f4053833b477076d4aff4,
title = "α-Methyldopa, α-methyldopamine and α-methylnoradrenaline: Substrates for the thermolabile form of human platelet phenol sulphotransferase",
abstract = "Sulphate conjugation catalyzed by phenol sulphotransferase (PST) is an important pathway in the catabolism of α-methyldopa (MD). Variations in PST activity in an easily obtained tissue such as the human platelet might reflect individual differences in the sulphate conjugation of MD in other organs and tissues. There are at least two forms of human platelet PST, a thermolabile form for which dopamine is a substrate and a thermostable form for which low concentrations of phenol can serve as a substrate. MD, α-methyldopamine (MDA) and α-methylnoradrenaline (MNA) were tested as substrates for human platelet PST. All three were substrates for the thermolabile form of the enzyme and none were substrates for the thermostable form of PST. Apparent Michaelis-Menten (K(m)) values for MD, MDA and MNA were 5.5, 0.014 and 0.28 mM, respectively. Apparent K(m) values for 3'-phosphoadenosine-5'-phosphosulphate, the sulphate donor for the reaction, were 0.08, 0.13 and 0.10 μM, respectively, for the three catechol substrates. The pH optima for the reaction were 7.5 for MD and 6.5 for both MDA and MNA. When platelet homogenates from 20 individual subjects were tested, there were significant correlations between PST activities measured with dopamine and those measured with MD, MDA and MNA (r = 0.54, 0.98 and 0.93, P < 0.02, < 0.001, and < 0.001, respectively), but not between activities measured with low concentrations of phenol and those measured with MD, MDA and MNA (r = 0.021, 0.045 and 0.046, respectively). These results were also compatible with the conclusion that MD, MDA and MNA were substrates for the thermolabile form of platelet PST. These observations will make it possible to test the hypothesis that variations in the activity of the thermolabile form of platelet PST may reflect individual differences in the sulphate conjugation of MD, MDA and MNA.",
author = "G. Mwaluko and Weinshilboum, {Richard M}",
year = "1982",
language = "English (US)",
volume = "14",
pages = "231--239",
journal = "British Journal of Clinical Pharmacology",
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T1 - α-Methyldopa, α-methyldopamine and α-methylnoradrenaline

T2 - Substrates for the thermolabile form of human platelet phenol sulphotransferase

AU - Mwaluko, G.

AU - Weinshilboum, Richard M

PY - 1982

Y1 - 1982

N2 - Sulphate conjugation catalyzed by phenol sulphotransferase (PST) is an important pathway in the catabolism of α-methyldopa (MD). Variations in PST activity in an easily obtained tissue such as the human platelet might reflect individual differences in the sulphate conjugation of MD in other organs and tissues. There are at least two forms of human platelet PST, a thermolabile form for which dopamine is a substrate and a thermostable form for which low concentrations of phenol can serve as a substrate. MD, α-methyldopamine (MDA) and α-methylnoradrenaline (MNA) were tested as substrates for human platelet PST. All three were substrates for the thermolabile form of the enzyme and none were substrates for the thermostable form of PST. Apparent Michaelis-Menten (K(m)) values for MD, MDA and MNA were 5.5, 0.014 and 0.28 mM, respectively. Apparent K(m) values for 3'-phosphoadenosine-5'-phosphosulphate, the sulphate donor for the reaction, were 0.08, 0.13 and 0.10 μM, respectively, for the three catechol substrates. The pH optima for the reaction were 7.5 for MD and 6.5 for both MDA and MNA. When platelet homogenates from 20 individual subjects were tested, there were significant correlations between PST activities measured with dopamine and those measured with MD, MDA and MNA (r = 0.54, 0.98 and 0.93, P < 0.02, < 0.001, and < 0.001, respectively), but not between activities measured with low concentrations of phenol and those measured with MD, MDA and MNA (r = 0.021, 0.045 and 0.046, respectively). These results were also compatible with the conclusion that MD, MDA and MNA were substrates for the thermolabile form of platelet PST. These observations will make it possible to test the hypothesis that variations in the activity of the thermolabile form of platelet PST may reflect individual differences in the sulphate conjugation of MD, MDA and MNA.

AB - Sulphate conjugation catalyzed by phenol sulphotransferase (PST) is an important pathway in the catabolism of α-methyldopa (MD). Variations in PST activity in an easily obtained tissue such as the human platelet might reflect individual differences in the sulphate conjugation of MD in other organs and tissues. There are at least two forms of human platelet PST, a thermolabile form for which dopamine is a substrate and a thermostable form for which low concentrations of phenol can serve as a substrate. MD, α-methyldopamine (MDA) and α-methylnoradrenaline (MNA) were tested as substrates for human platelet PST. All three were substrates for the thermolabile form of the enzyme and none were substrates for the thermostable form of PST. Apparent Michaelis-Menten (K(m)) values for MD, MDA and MNA were 5.5, 0.014 and 0.28 mM, respectively. Apparent K(m) values for 3'-phosphoadenosine-5'-phosphosulphate, the sulphate donor for the reaction, were 0.08, 0.13 and 0.10 μM, respectively, for the three catechol substrates. The pH optima for the reaction were 7.5 for MD and 6.5 for both MDA and MNA. When platelet homogenates from 20 individual subjects were tested, there were significant correlations between PST activities measured with dopamine and those measured with MD, MDA and MNA (r = 0.54, 0.98 and 0.93, P < 0.02, < 0.001, and < 0.001, respectively), but not between activities measured with low concentrations of phenol and those measured with MD, MDA and MNA (r = 0.021, 0.045 and 0.046, respectively). These results were also compatible with the conclusion that MD, MDA and MNA were substrates for the thermolabile form of platelet PST. These observations will make it possible to test the hypothesis that variations in the activity of the thermolabile form of platelet PST may reflect individual differences in the sulphate conjugation of MD, MDA and MNA.

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