Lorenz Mario, Paul Friedemann, Moobed Minoo, Baumann Gert, Zimmermann Benno F, Stangl Karl, Stangl Verena
Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charite - Universitätsmedizin Berlin, Schumannstr. 20-21, 10117 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany.
NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, Germany.
Eur J Pharmacol. 2014 Oct 5;740:645-51. doi: 10.1016/j.ejphar.2014.06.014. Epub 2014 Jun 24.
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.
儿茶酚-O-甲基转移酶（COMT）通过O-甲基化使许多内源性和外源性化合物失活。因此，它是代谢途径中的一种主要酶，在激素和药物代谢中具有重要的生物学功能。茶儿茶素表没食子儿茶素-3-没食子酸酯（EGCG）在体外已知可抑制COMT酶活性。基于有益的体外研究结果，EGCG被广泛用于多种人类疾病的人体干预研究。由于其生物利用度低，经常应用较高剂量的EGCG，这可能会损害体内的COMT活性。在24名健康人类志愿者（14名女性，10名男性）的红细胞（RBC）中测定了四种功能性COMT单核苷酸多态性（SNP）的酶活性。受试者补充了750mg的EGCG，并在干预前和干预后2小时测量了EGCG血浆水平和红细胞中的COMT酶活性。SNP rs4680中的纯合Val→Met替代导致COMT活性显著降低。红细胞中的COMT酶活性也受到其他三种COMT多态性的影响。干预后EGCG血浆水平显著升高。它们不受任何COMT SNP和不同酶活性的影响。摄入750mg EGCG不会导致COMT活性受损。然而，摄入EGCG后COMT活性显著增加了24%。这些结果表明，补充高剂量的EGCG不会损害COMT的活性。因此，它可能不会干扰COMT介导的外源性和内源性COMT底物的代谢和消除。
