Rapid conversion of tea catechins to monomethylated products by rat liver cytosolic catechol-O-methyltransferase

1. The metabolic O-methylation of several catechol-containing tea polyphenols by rat liver cytosolic catechol-O-methyltransferase (COMT) has been studied. 2. When (-)-epicatechin was used as substrate, its O-merthylation showed dependence on incubation time, cytosolic protein concentration, incubation pH and concentration of S-adenosyl-L-methionine. The O-methylation of increasing concentrations of (-)-epicatechin followed typical Michaelis-Menten kinetics, and the apparent Km and Vmax were 51 microM and 2882 pmol mg protein(-1) min(-1), respectively, at pH 7.4, and were 17 microM and 2093 pmol mg protein(-1) min(-1), respectively, at pH 10.0. 3. Under optimized conditions for in vitro O-methylation, (-)-epicatechin, (+)-epicatechin and (-)-epigallocatechin were rapidly O-methylated by rat liver cytosol. In comparison, (-)-epicatechin gallate and (-)-epigallocatechin gallate vere O-methylated at significantly lower rates under the same reaction conditions. catalysed O-methylation of (-)-epicatechin and (-)-epigallocatechin was inhibited in a concentration-dependent manner by S-adenosyl-L-homocysteine, a demethylated product of S-adenosyl-L-methionine. The IC50 was approximately 10 microM. 5. In summary, the results showed that several catechol-containing tea polyphenols were rapidly O-methylated by rat liver cytosolic COMT. These observations raise the possibility that some of the biological effects of tea polyphenols may be exerted by their O-methylated products or may result from their potential inhibition of the COMT-catalysed O-methylation of endogenous catecholamines and catechol oestrogens.