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Noncompetitive inhibition of proton-coupled folate transporter by myricetin

Mai Furumiya1, Katsuhisa Inoue, Chihiro Nishijima

  • 1Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University.

Drug Metabolism and Pharmacokinetics
|February 5, 2014
PubMed

Insights

Myricetin, a flavonoid, noncompetitively inhibits folate absorption by targeting the proton-coupled folate transporter (PCFT). This interaction may affect folate and antifolate drug uptake, necessitating caution with flavonoid consumption.

Area of Science:

  • Nutritional Biochemistry
  • Molecular Pharmacology
  • Gastrointestinal Physiology

Background:

  • Flavonoids are plant-derived compounds with various biological activities.
  • Myricetin has been implicated in interfering with intestinal nutrient transport.
  • The proton-coupled folate transporter (PCFT) is crucial for folate absorption in the intestine.

Purpose of the Study:

  • To investigate the inhibitory effect of myricetin on the intestinal folate transport system.
  • To determine the mechanism by which myricetin affects folate uptake via PCFT.

Main Methods:

  • Folate uptake assays were performed using Caco-2 cells (intestinal epithelial model).
  • Folate transport was studied in Madin-Darby canine kidney II (MDCKII) cells stably expressing human PCFT.
  • Kinetic analysis (Michaelis constant, inhibition constant) was used to characterize the interaction.

Main Results:

  • Myricetin noncompetitively inhibited folate transport in Caco-2 cells (Ki = 61 µM).
  • Myricetin also noncompetitively inhibited folate transport mediated by human PCFT in MDCKII cells (Ki = 130 µM).
  • Epigallocatechin-3-gallate demonstrated similar noncompetitive inhibitory effects.

Conclusions:

  • Myricetin inhibits intestinal folate transport by acting noncompetitively on PCFT.
  • Caution is advised regarding the dietary intake of myricetin and related flavonoids to ensure adequate folate and antifolate drug absorption.

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