Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 282, Issue 6, Pages C1512-C1517Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00547.2001
Keywords
SLC19A transporters; thiamine-responsive megaloblastic anemia; thiamine pyrophosphate; thiamine homeostasis; vitamin B-1 uptake
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Funding
- NCI NIH HHS [CA-82621] Funding Source: Medline
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Although the reduced folate carrier RFC1 and the thiamine transporters THTR-1 and THTR-2 share similar to40% 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 similar to50% 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.
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