Noncompetitive Inhibition of Proton-Coupled Folate Transporter by Myricetin

Abstract

Summary: Myricetin is a flavonoid that has recently been suggested to interfere with the intestinal folate transport system. The present study was conducted to examine that possibility, focusing on its inhibitory effect on proton-coupled folate transporter (PCFT) as the molecular entity of the transport system. The uptake transport of folate was first examined in the Caco-2 cell as an intestinal epithelial cell model, and its carrier-mediated component, of which the Michaelis constant (K_m) was 0.407 µM, was found to be noncompetitively inhibited by myricetin with the inhibition constant (K_i) of 61 µM. Consistent with that, folate transport by human PCFT stably expressed in Madin-Darby canine kidney II (MDCKII) cells, of which the K_m was 1.246 µM, was also noncompetitively inhibited by myricetin with the K_i of 130 µM. Thus, myricetin was suggested to inhibit intestinal folate transport by acting noncompetitively on PCFT, although the K_m and K_i were similarly shifted to some extent to be smaller in Caco-2 cells. Finally, epigallocatechin-3-gallate was also suggested to act in a noncompetitive manner as an inhibitory flavonoid. Care may need to be taken, therefore, in the ingestion of myricetin and some flavonoids to maintain the absorption of folate and antifolate drugs.