PT  - JOURNAL ARTICLE
AU  - C. R. CREVELING
AU  - N. MORRIS
AU  - H. SHIMIZU
AU  - H. H. ONG
AU  - J. DALY
TI  - Catechol <em>O</em>-Methyltransferase
DP  - 1972 Jul 01
TA  - Molecular Pharmacology
PG  - 398--409
VI  - 8
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/8/4/398.short
4100  - http://molpharm.aspetjournals.org/content/8/4/398.full
SO  - Mol Pharmacol1972 Jul 01; 8
AB  - The methylation of substituted catechols catalyzed by catechol O-methyltransferase (EC 2.1.1.6) with S-adenosylmethionine as methyl donor results in the formation of a mixture of m- and p-O-methyl derivatives. A variety of evidence indicates that a single enzyme catalyzes the formation of both O-methylated products. The ratio of O-methylated products and values for the apparent Km and Vmax obtained with a wide variety of substituted mono-, bi-, and polycyclic catechols, including catecholamines, amino acids, acids, esters, amides, and ketones, are presented. The results provide a guide for the prediction of the ratio of products to be expected with other catechols. The magnitude of the ratio of the O-methylated products is dependent upon the concentration of divalent cation, the pH of the medium, and the nature and position of the substituents on the catechol ring. It is proposed that the magnitude of this ratio results from the orientation in which the substrate binds to the enzyme. Polar groups, either anionic or cationic in nature, militate against binding of the catechol ring in the orientations that results in p-O-methylation. The ratio of O-methylated isomers obtained with various catecholamines and amino acids is discussed with respect to the probable preferred conformations of the side chains in these substrates. ACKNOWLEDGMENTS The authors wish to acknowledge the capable technical assistance of Sister Rita Sherri and Mr. Anthony Di Sant-Agnese.