TY - JOUR
T1 - Reduced folate carrier transports thiamine monophosphate
T2 - An alternative route for thiamine delivery into mammalian cells
AU - Zhao, Rongbao
AU - Gao, Feng
AU - David Goldman, I.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - SLC19A transporters
KW - Thiamine homeostasis
KW - Thiamine pyrophosphate
KW - Thiamine-responsive megaloblastic anemia
KW - Vitamin B uptake
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U2 - 10.1152/ajpcell.00547.2001
DO - 10.1152/ajpcell.00547.2001
M3 - Article
C2 - 11997266
AN - SCOPUS:0036085901
SN - 0363-6143
VL - 282
SP - C1512-C1517
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 6 51-6
ER -