RRC ID 61153
Author Yamashiro T, Yasujima T, Ohta K, Inoue K, Yuasa H.
Title Identification of the amino acid residue responsible for the myricetin sensitivity of human proton-coupled folate transporter.
Journal Sci Rep
Abstract Human proton-coupled folate transporter (hPCFT/SLC46A1) has recently been found to be inhibited by myricetin by a sustained mechanism, raising a concern that the inhibition might lead to malabsorption of folates in the intestine, where hPCFT works for their epithelial uptake. However, rat PCFT (rPCFT) has more recently been found not to be inhibited by myricetin. Prompted by this finding, we attempted to determine the amino acid residue involved in that by analyses comparing between hPCFT and rPCFT. In the initial analysis, chimeric constructs prepared from hPCFT and rPCFT were examined for myricetin sensitivity to determine the hPCFT segment involved in the sensitivity. Focusing on the thereby determined segment from 83rd to 186th amino acid residue, hPCFT mutants having a designated amino acid residue replaced with its counterpart in rPCFT were prepared for the subsequent analysis. Among them, only G158N-substituted hPCFT was found to be transformed to be insensitive to myricetin and, accordingly, oppositely N158G-substituted rPCFT was transformed to be sensitive to myricetin. These results indicate the critical role of Gly158 in the myricetin sensitivity of hPCFT. This finding would help advance the elucidation of the mechanism of the myricetin-induced inhibition of hPCFT and manage the potential risk arising from that.
Volume 9(1)
Pages 18105
Published 2019-12-2
DOI 10.1038/s41598-019-54367-9
PII 10.1038/s41598-019-54367-9
PMID 31792273
PMC PMC6889420
MeSH Amino Acid Substitution Flavonoids / pharmacology* Folic Acid / pharmacokinetics Glycine / genetics* HEK293 Cells Humans Intestinal Absorption / drug effects Intestinal Absorption / physiology Mutagenesis, Site-Directed Proton-Coupled Folate Transporter / genetics* Proton-Coupled Folate Transporter / metabolism Recombinant Proteins / genetics Recombinant Proteins / metabolism
IF 3.998
DNA material pCI-neo-bPCFT (RDB18233) pCI-neo-mPCFT (RDB18234) pCI-neo-agmPCFT (RDB18232)
Human and Animal Cells MDBK(RCB0180) RAW 264(RCB0535)