The activity of catechol-O-methyltransferase (COMT) is not impaired by high doses of epigallocatechin-3-gallate (EGCG) in vivo

Eur J Pharmacol. 2014 Oct 5;740:645-51. doi: 10.1016/j.ejphar.2014.06.014. Epub 2014 Jun 24.

Abstract

Catechol-O-methyltransferase (COMT) inactivates many endogenous and exogenous compounds by O-methylation. Therefore, it represents a major enzyme of the metabolic pathway with important biological functions in hormonal and drug metabolism. The tea catechin epigallocatechin-3-gallate (EGCG) is known to inhibit COMT enzymatic activity in vitro. Based on beneficial in vitro results, EGCG is extensively used in human intervention studies in a variety of human diseases. Owing to its low bioavailability, rather high doses of EGCG are frequently applied that may impair COMT activity in vivo. Enzymatic activities of four functional COMT single-nucleotide polymorphisms (SNPs) were determined in red blood cells (RBCs) in 24 healthy human volunteers (14 women, 10 men). The subjects were supplemented with 750 mg of EGCG and EGCG plasma levels and COMT enzyme activities in erythrocytes were measured before and 2 h after intervention. The homozygous Val→Met substitution in the SNP rs4680 resulted in significantly decreased COMT activity. Enzymatic COMT activities in RBCs were also affected by the other three COMT polymorphisms. EGCG plasma levels significantly increased after intervention. They were not influenced by any of the COMT SNPs and different enzyme activities. Ingestion of 750 mg EGCG did not result in impairment of COMT activity. However, COMT activity was significantly increased by 24% after EGCG consumption. These results indicate that supplementation with a high dose of EGCG does not impair the activity of COMT. Consequently, it may not interfere with COMT-mediated metabolism and elimination of exogenous and endogenous COMT substrates.

Keywords: COMT; EGCG; Enzyme activity; Epigallocatechin gallate (PubChem CID: 65064); Erythrocytes; SNP.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catechin / analogs & derivatives*
  • Catechin / blood
  • Catechin / pharmacokinetics
  • Catechin / pharmacology
  • Catechol O-Methyltransferase / blood
  • Catechol O-Methyltransferase / genetics
  • Catechol O-Methyltransferase / metabolism*
  • Cells, Cultured
  • Erythrocytes / drug effects
  • Erythrocytes / enzymology
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide

Substances

  • Catechin
  • epigallocatechin gallate
  • COMT protein, human
  • Catechol O-Methyltransferase