The effect of hydrogen ion concentration on enzymatic O-methylation of catechol estrogens. Clinical analysis on steroids. XI.

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Abstract
Incubation of 2-hydroxyestradiol with rat liver homogenate in the presence of S-adenosyl-L-methionine and Mg2+ gave 2 isomeric monomethyl ethers, 2-methoxyestradiol and 2-hydroxyestradiol-3-methyl ether. The ratio of the 2-O-methyl ether to the 3-O-methyl ether formed was dependent on H ion concentration of the medium. At pH 6.0, the ratio was .apprx. 3-4, which decreased gradually with increasing pH; at pH > 7.0, the ratio was approaching unity. The pH dependency upon the product ratio was significant when 2,3,17.beta.-trihydroxyestra-1,3,5(10)-trien-6-one was used as a substrate, although the ratio was completely reversed in contrast with the result obtained with 2-hydroxyestradiol. At pH 6-7, the ratio of the 3-O-methyl ether to 2-O-methyl ether was .apprx. 6-8. With increasing pH of the medium, 2-O-methylation increased gradually and at over pH 8.0 the ratio became constant at about 3. Apparently rat liver catechol O-methyltransferase catalyzes the transfer of the methyl group from S-adenosyl-L-methionine to a more basic hydroxyl group of the 2 phenolic hydroxyl groups of estrogen catechols.