Reaction participants Show >> << Hide
- Name help_outline folate Identifier CHEBI:62501 Charge -2 Formula C19H17N7O6 InChIKeyhelp_outline OVBPIULPVIDEAO-LBPRGKRZSA-L SMILEShelp_outline Nc1nc2ncc(CNc3ccc(cc3)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)nc2c(=O)[nH]1 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,932 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:70159 | RHEA:70160 | RHEA:70161 | RHEA:70162 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
|
Publications
-
Structural basis of antifolate recognition and transport by PCFT.
Parker J.L., Deme J.C., Kuteyi G., Wu Z., Huo J., Goldman I.D., Owens R.J., Biggin P.C., Lea S.M., Newstead S.
Folates (also known as vitamin B9) have a critical role in cellular metabolism as the starting point in the synthesis of nucleic acids, amino acids and the universal methylating agent S-adenylsmethionine<sup>1,2</sup>. Folate deficiency is associated with a number of developmental, immune and neur ... >> More
Folates (also known as vitamin B9) have a critical role in cellular metabolism as the starting point in the synthesis of nucleic acids, amino acids and the universal methylating agent S-adenylsmethionine<sup>1,2</sup>. Folate deficiency is associated with a number of developmental, immune and neurological disorders<sup>3-5</sup>. Mammals cannot synthesize folates de novo; several systems have therefore evolved to take up folates from the diet and distribute them within the body<sup>3,6</sup>. The proton-coupled folate transporter (PCFT) (also known as SLC46A1) mediates folate uptake across the intestinal brush border membrane and the choroid plexus<sup>4,7</sup>, and is an important route for the delivery of antifolate drugs in cancer chemotherapy<sup>8-10</sup>. How PCFT recognizes folates or antifolate agents is currently unclear. Here we present cryo-electron microscopy structures of PCFT in a substrate-free state and in complex with a new-generation antifolate drug (pemetrexed). Our results provide a structural basis for understanding antifolate recognition and provide insights into the pH-regulated mechanism of folate transport mediated by PCFT. << Less
Nature 595:130-134(2021) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
-
Cloning and functional characterization of the proton-coupled electrogenic folate transporter and analysis of its expression in retinal cell types.
Umapathy N.S., Gnana-Prakasam J.P., Martin P.M., Mysona B., Dun Y., Smith S.B., Ganapathy V., Prasad P.D.
<h4>Purpose</h4>In a prior study the cellular uptake of folate was investigated in the retina. Recently, a new proton-coupled folate transporter (PCFT) in human intestine was reported. In the present study, the expression of this novel transporter in the retina was determined, the mouse orthologue ... >> More
<h4>Purpose</h4>In a prior study the cellular uptake of folate was investigated in the retina. Recently, a new proton-coupled folate transporter (PCFT) in human intestine was reported. In the present study, the expression of this novel transporter in the retina was determined, the mouse orthologue was cloned from retinal tissue, and its transport function was characterized.<h4>Methods</h4>RT-PCR and folate uptake measurements were used to detect the expression of PCFT in mouse retina and in retinal cell types. The expression of PCFT mRNA in intact retina was investigated by in situ hybridization. Mouse PCFT cDNA was cloned, and its transport characteristics were analyzed by electrophysiological methods after expression of the cloned transporter in Xenopus laevis oocytes.<h4>Results</h4>RT-PCR showed expression of PCFT mRNA in both neural retina and RPE eye cup. In situ hybridization detected PCFT mRNA in all retinal cell layers. Proton-coupled folate uptake was detectable in primary cultures of ganglion, Müller, and RPE cells of mouse retina and in RPE, ganglion, and Müller cells of human or rat origin. In X. laevis oocytes expressing the cloned mouse PCFT, folate and its derivatives methotrexate and 5-methyltetrahydrofolate induced H(+)-coupled inward currents with K(t) values of 1.2 +/- 0.1, 4.6 +/-0.5, and 3.5 +/-0.8 microM, respectively. The transport process showed an H(+)-folate stoichiometry of 1:1, suggesting that PCFT transports the zwitterionic form of folate.<h4>Conclusions</h4>This is the first report on the expression of PCFT in the retina. All cell layers of the retina express this transporter. Mouse PCFT, cloned from retina, mediates H(+)-coupled electrogenic transport of folate and its derivatives. << Less
Invest. Ophthalmol. Vis. Sci. 48:5299-5305(2007) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.