ArticleMolecular pharmacology2013
Inhibition of the proton-coupled folate transporter (PCFT-SLC46A1) by bicarbonate and other anions.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Discovery of Tumor-Targeted 6-Methyl Substituted Pemetrexed and Related Antifolates with Selective Loss of RFC Transport.ACS medicinal chemistry letters · 2023Article
- Biology and therapeutic applications of the proton-coupled folate transporter.Expert opinion on drug metabolism & toxicology · 2022Article
- The evolving biology of the proton-coupled folate transporter: New insights into regulation, structure, and mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Review
- Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer.Cancers · 2021Review
- Therapeutic Targeting of Mitochondrial One-Carbon Metabolism in Cancer.Molecular cancer therapeutics · 2020Review
- The Key Role of Purine Metabolism in the Folate-Dependent Phenotype of Autism Spectrum Disorders: An In Silico Analysis.Metabolites · 2020Article
- Concentrative Transport of Antifolates Mediated by the Proton-Coupled Folate Transporter (SLC46A1); Augmentation by a HEPES Buffer.Molecular pharmacology · 2018Article
- The promise and challenges of exploiting the proton-coupled folate transporter for selective therapeutic targeting of cancer.Cancer chemotherapy and pharmacology · 2018Review
- The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption.Molecular aspects of medicine · 2017Review
- The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
- Enhanced receptor-mediated endocytosis and cytotoxicity of a folic acid-desacetylvinblastine monohydrazide conjugate in a pemetrexed-resistant cell line lacking folate-specific facilitative carriers but with increased folate receptor expression.Molecular pharmacology · 2014Article
- Biology of the major facilitative folate transporters SLC19A1 and SLC46A1.Current topics in membranes · 2014Review
- The intestinal absorption of folates.Annual review of physiology · 2014Review
- The proton-coupled folate transporter: physiological and pharmacological roles.Current opinion in pharmacology · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The proton-coupled folate transporter (PCFT) plays a key role in intestinal folate absorption, and loss-of-function mutations in the gene encoding this transporter are the molecular basis for hereditary folate malabsorption. Using a stable transfectant with high expression of PCFT, physiologic levels of bicarbonate produced potent and rapidly reversible inhibition of PCFT-mediated transport at neutral pH. Bisulfite and nitrite also inhibited PCFT function at neutral pH, whereas sulfate, nitrate, and phosphate had no impact at all. At weakly acidic pH (6.5), bisulfite and nitrite exhibited much stronger inhibition of PCFT-mediated transport, whereas sulfate and nitrate remained noninhibitory. Inhibition by bisulfite and nitrite at pH 6.5 was associated with a marked decrease in the influx Vmax and collapse of the transmembrane proton gradient attributed to the diffusion of the protonated forms into these cells. Monocarboxylates such as pyruvate and acetate also collapsed the pH gradient and were also inhibitory, whereas citrate and glycine neither altered the proton gradient nor inhibited PCFT-mediated transport. These observations add another dimension to the unfavorable pH environment for PCFT function in systemic tissues: the presence of high concentrations of bicarbonate.
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Registered trials
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