Tyrosine phenol-lyase inhibitor quercetin reduces fecal phenol levels in mice

Author:

Kobayashi Takuma1ORCID,Oishi Shiori1ORCID,Matsui Misaki2,Hara Kodai3ORCID,Hashimoto Hiroshi3ORCID,Watanabe Kenji3ORCID,Yoshioka Yasukiyo12ORCID,Miyoshi Noriyuki12ORCID

Affiliation:

1. Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka , Shizuoka, 4228526 , Japan

2. School of Food and Nutritional Sciences, University of Shizuoka , Shizuoka, 4228526 , Japan

3. Department of Pharmaceutical Sciences, University of Shizuoka , Shizuoka, 4228526 , Japan

Abstract

Abstract Tyrosine phenol-lyase (TPL), which is expressed in intestinal bacteria, catalyzes the formation of phenol from the substrate L-Tyr. Bacterial metabolite phenol and the sulfate conjugate (phenyl sulfate) are known as a type of uremic toxins, some of which exert cytotoxicity. Therefore, pathologically elevated phenol and phenyl sulfate levels are strongly implicated in the etiology and outcome of uremia. In this study, we explored the inhibitory effects of dietary polyphenols on TPL-catalyzed phenol production using a TPL activity assay. Quercetin, one of the most popular polyphenols, exhibited the strongest inhibitory activity (Ki = 19.9 µM). Quercetin competitively inhibited TPL, and its activity was stronger than that of a known TPL inhibitor (Tyr analog; 2-aza-Tyr, Ki = 42.0 µM). Additionally, quercetin significantly inhibited phenol production in TPL-expressing bacterial cultures (Morganella morganii and Citrobacter koseri) and Tyr-rich (5%) diet-fed C57BL/6J mouse feces. Our findings suggest that quercetin is the most promising polyphenol for reducing phenol levels. Because quercetin has a low gastrointestinal absorption rate, TPL inhibition in the intestinal tract by quercetin may be an effective strategy for treating uremia.

Funder

Ministry of Education

MEXT

Publisher

Oxford University Press (OUP)

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