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Vol. 28, Issue 9, 1024-1030, September 2000
Department of Basic Pharmaceutical Sciences, College of Pharmacy,
University of South Carolina, Columbia, South Carolina (B.T.Z.) and
Laboratory for Cancer Research, Department of Chemical Biology, College
of Pharmacy, Rutgers In the present study, we evaluated the metabolic
O-methylation of several catechol-containing tea
polyphenols by human placental catechol-O-methyltransferase (COMT). (
The State University of New Jersey, Piscataway,
New Jersey (U.K.P., M.X.C., A.H.C.)
)-Epicatechin,
(+)-epicatechin, and ()-epigallocatechin were good substrates for
metabolic O-methylation by placental cytosolic COMT
(150-500 pmol/mg of protein/min), but ()-epicatechin gallate and
()-epigallocatechin gallate were O-methylated at much
lower rates (<50 pmol/mg of protein/min). When ()-epicatechin was
used as substrate, its O-methylation by human placental
COMT showed dependence on incubation time, cytosolic protein
concentration, incubation pH, and concentration of
S-adenosyl-L-methionine (the methyl donor).
Analysis of cytosolic COMT from six human term placentas showed that
the O-methylation of increasing concentrations of
()-epicatechin or ()-epigallocatechin follows typical
Michaelis-Menten kinetics, with Km and
Vmax values of 2.2 to 8.2 µM and 132 to
495 pmol/mg of protein/min for ()-epicatechin and 3.9 to 6.7 µM and
152 to 310 pmol/mg of protein/min for ()-epigallocatechin, respectively. Additional analysis revealed that COMT-catalyzed O-methylation of ()-epicatechin and
()-epigallocatechin was strongly inhibited in a
concentration-dependent manner by
S-adenosyl-L-homocysteine (IC50 = 3.2-5.7 µM), a demethylated product of
S-adenosyl-L-methionine. This inhibition by
S-adenosyl-L-homocysteine follows a mixed
(competitive plus noncompetitive) mechanism of enzyme inhibition. In
summary, several catechol-containing tea polyphenols are rapidly
O-methylated by human placental cytosolic COMT. This
metabolic O-methylation is subject to strong inhibitory
regulation by S-adenosyl-L-homocysteine, which is formed in large quantities during the
O-methylation of tea polyphenols.
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