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In this study, we characterized the enzymology of cytosolic catechol-O-methyltransferase (COMT)-catalyzed …


Biology Articles » Biochemistry » Enzymology » Enzymology of Methylation of Tea Catechins and Inhibition of Catechol-O-methyltransferase by ()-Epigallocatechin Gallate

Abstract
- Enzymology of Methylation of Tea Catechins and Inhibition of Catechol-O-methyltransferase by ()-Epigallocatechin Gallate

Enzymology of Methylation of Tea Catechins and Inhibition of Catechol-O-methyltransferase by (-)-Epigallocatechin Gallate

Hong Lu, Xiaofeng Meng, and Chung S. Yang

Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey

Drug Metabolism and Disposition, Vol. 31, Issue 5, 572-579, May 2003.

 

Abstract

(-)-Epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) are the major polyphenolic constituents in green tea. Inthis study, we characterized the enzymology of cytosolic catechol-O-methyltransferase(COMT)-catalyzed methylation of EGCG and EGC in humans, mice,and rats. At 1 µM, EGCG was readily methylated by liver cytosolicCOMT to 4"-O-methyl-EGCG and then to 4',4"-di-O-methyl-EGCG; EGCwas methylated to 4'-O-methyl-EGC. The Km and Vmax values forEGC methylation were higher than EGCG; for example, with humanliver cytosol, the Km were 4.0 versus 0.16 µM and Vmax were 1.28 versus 0.16 nmol/mg/min. Rat liver cytosol had higher COMT activitythan that of humans or mice. The small intestine had lower specificactivity than the liver in the methylation of EGCG and EGC. Glucuronidationon the B-ring or the D-ring of EGCG greatly inhibited the methylationon the same ring, but glucuronidation on the A-ring of EGCG orEGC did not affect their methylation. Using EGC and 3,4-dihydroxy-L-phenylalanineas substrates, EGCG, 4"-O-methyl-EGCG, and 4',4"-di-O-methyl-EGCGwere all potent inhibitors (IC50 ~0.2 µM) of COMT. The COMT-inhibitingactivity of (-)-EGCG-3'-O-glucuronide was similar to EGCG, but(-)-EGCG-4"-O-glucuronide was less potent. The present work providesbasic information on the methylation of EGCG and suggests thatEGCG may inhibit COMT-catalyzed methylation of endogenous andexogenouscompounds.



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