Interactions Between Estrogens and Catechol Amines III. Studies on the Methylation of Catechol Estrogens, Catechol Amines and other Catechols by the Catechol-O-Methyltransferase1 of Human Liver

作者：Peter Ball, R. Knüppen, Margitta Haupt, Heinz Breuer · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：1972 · DOI：10.1210/jcem-34-4-736 · 被引用次数：281 · 研究领域：Estrogen and related hormone effects

The substrate specificity of the catechol-O-methyltransferase, purified from human liver 380-fold, has been tested with a variety of compounds. Catechol estrogens, as well as catechol amines are methylated to their corresponding monomethyl ethers. The relation of the rates of methylation of catechol estrogens and catechol amines depended on enzyme and substrate concentration; under standard assay conditions, 2-hydroxy-17β-estradiol was the preferred substrate for the enzyme, as compared with epinephrine and other catechols tested. Km-values for 2-hydroxy-17β-estradiol were 15 μm, for 2-hydroxy-estrone 20 μm, for 2-hydroxy-estriol 25 μm and for-hydroxy-estrone 20 μm. For epinephrine and norepinephrine, Km-values of 300 μm and 200 μm, respectively, were obtained. The ratio of formation of the isomeric monomethyl ethers of catechol estrogens varied between 1.3 and 95, depending on the substrate incubated. On the basis of kinetic studies with different enzyme preparations, different inhibitors and different concentrations of the substrates, it is concluded that both catechol estrogens and catechol amines are methylated by the same Catechol-O-methyltransferase. The enzymic methylation of epinephrine was inhibited competitively by 2- and 4-hydroxylated estrogens; the Ki-values were 7.0 μm for 2-hydroxy-17β-estradiol, 8.5 μm for 2-hydroxy-estrone, 12.2 μm for 2-hydroxy-estriol, 50 μm for 4-hydroxy-estrone and, for comparison, 154 μm for the addition of norepinephrine. A non-competit...