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Molecular Pharmacology, Vol 19, 130-133, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Phenol Ionization in Dopa Determines the Site of Methylation by Catechol-O-Methyltransferase

GUNTER FIRNAU 1, SUDESH SOOD 1, RICHARD PANTEL 1, and STEPHEN GARNETT 1

1 McMaster University Medical Centre, Department of Nuclear Medicine, Hamilton, Ontario, Canada L8S 4J9

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) with S-adenosylmethionine as the methyl donor catalyzes preferentially p-O-methylation when 5-fluorodopa is the substrate. The rate of this reaction is characterized by a Km of 0.4 ± 0.2 mmole/liter and a Vmax of 27 ± 11 mmoles/mg of COMT per minute at pH 7.9. We conclude that these results are a consequence of fluorine-induced ionization at the p-hydroxyl group.

Note:
ACKNOWLEDGMENT We are grateful to Dr. C. R. Creveling, Natonal Institutes of Health, Bethesda, Md., who provided 3-(4-hydroxy-3-methoxyphenyl)-L-alanine.

Submitted on December 7, 1979
Accepted on September 3, 1980







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