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

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