TY - JOUR
T1 - The proton-coupled folate transporter
T2 - Physiological and pharmacological roles
AU - Zhao, Rongbao
AU - Goldman, I. David
N1 - Funding Information:
This work is supported by a grant from National Institutes of Health National Cancer , CA82621 . The authors wish to thank Dr. Lorenzo Agoni for composing the figure.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1016/j.coph.2013.09.011
DO - 10.1016/j.coph.2013.09.011
M3 - Review article
C2 - 24383099
AN - SCOPUS:84888198861
SN - 1471-4892
VL - 13
SP - 875
EP - 880
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
IS - 6
ER -