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

Abstract

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 -methylation 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 K m and V max were 51µM and 2882 pmol mg protein -1 min -1, respectively, at pH 7.4, and were 17 µM 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 were O -methylated at significantly lower rates under the same reaction conditions. 4. COMT-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 IC 50 was 10µM. 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.