The proton-coupled folate transporter

Physiological and pharmacological roles

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Recent studies have identified the proton-coupled folate transporter (PCFT) as the mechanism by which folates are absorbed across the apical brush-border membrane of the small intestine and across the basolateral membrane of the choroid plexus into the cerebrospinal fluid. Both processes are defective when there are loss-of-function mutations in this gene as occurs in the autosomal recessive disorder hereditary folate malabsorption. Because this transporter functions optimally at low pH, antifolates are being developed that are highly specific for PCFT in order to achieve selective delivery to malignant cells within the acidic environment of solid tumors. PCFT has a spectrum of affinities for folates and antifolates that narrows and increases at low pH. Residues have been identified that play a role in folate and proton binding, proton coupling, and oscillation of the carrier between its conformational states.

Original languageEnglish (US)
Pages (from-to)875-880
Number of pages6
JournalCurrent Opinion in Pharmacology
Volume13
Issue number6
DOIs
StatePublished - 2013

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Proton-Coupled Folate Transporter
Folic Acid
Folic Acid Antagonists
Pharmacology
Protons
Choroid Plexus
Membranes
Microvilli
Small Intestine
Cerebrospinal Fluid
Mutation
Genes
Neoplasms

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

The proton-coupled folate transporter : Physiological and pharmacological roles. / Zhao, Rongbao; Goldman, I. David.

In: Current Opinion in Pharmacology, Vol. 13, No. 6, 2013, p. 875-880.

Research output: Contribution to journalArticle

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