The H(+)-dependent reduced folate carrier 1 of humans and the sodium-dependent methotrexate carrier-1 of the rat are orthologs |
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Authors: | Kneuer Carsten Honscha Walther |
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Institution: | Institute of Pharmacology, Pharmacy and Toxicology, An den Tierkliniken 15, University of Leipzig, 04103 Leipzig, Germany. |
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Abstract: | Previously, two different carrier systems for uptake of reduced folates and the antifolate methotrexate (Mtx) were described: the pH-dependent folate sensitive reduced folate carrier 1 (RFC1) from human, hamster and mouse and a sodium-dependent and folate insensitive Mtx carrier-1 (MTX-1) from rat. It was found that all critical residues of the homologous amino acid sequence were identical. RFC1- as well as MTX-1-mediated uptake of a marker substrate into suitable human and rat cell lines increased with proton concentration, was sodium-dependent at neutral pH, and inhibited by folate at acidic pH. It is concluded that RFC1 and MTX-1 are orthologs. |
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