Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells

• Published in: American Journal of Physiology: Cell Physiology Vol. 282; no. 6; pp. C1512 - C1517
• Main Authors: Zhao, Rongbao, Gao, Feng, Goldman, I. David
• Format: Journal Article
• Language: English
• Published: United States 01.06.2002
• Subjects: Animals; Biological Transport - drug effects; Carrier Proteins - metabolism; Dose-Response Relationship, Drug; Leukemia L1210 - drug therapy; Leukemia L1210 - metabolism; Membrane Proteins - metabolism; Membrane Transport Proteins; Methotrexate - pharmacokinetics; Methotrexate - pharmacology; Mice; Thiamine - metabolism; Thiamine - pharmacology; Thiamine Monophosphate - metabolism; Thiamine Monophosphate - pharmacokinetics; Tumor Cells, Cultured
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00547.2001

Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461 Although the reduced folate carrier RFC1 and the thiamine transporters THTR-1 and THTR-2 share ~40% of their identity in protein sequence, RFC1 does not transport thiamine and THTR-1 and THTR-2 do not transport folates. In the present study, we demonstrate that transport of thiamine monophosphate (TMP), an important thiamine metabolite present in plasma and cerebrospinal fluid, is mediated by RFC1 in L1210 murine leukemia cells. Transport of TMP was augmented by a factor of five in cells (R16) that overexpress RFC1 and was markedly inhibited by methotrexate, an RFC1 substrate, but not by thiamine. At a near-physiological concentration (50 nM), TMP influx mediated by RFC1 in wild-type L1210 cells was ~50% of thiamine influx mediated by thiamine transporter(s). Within 1 min, the majority of TMP transported into R16 cells was hydrolyzed to thiamine with a component metabolized to thiamine pyrophosphate, the active enzyme cofactor. These data suggest that RFC1 may be one of the alternative transport routes available for TMP in some tissues when THTR-1 is mutated in the autosomal recessive disorder thiamine-responsive megaloblastic anemia. SLC19A transporters; thiamine-responsive megaloblastic anemia; thiamine pyrophosphate; thiamine homeostasis; vitamin B 1 uptake