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首页> 外文期刊>American Journal of Physiology >Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells.
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Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells.

机译：减少的叶酸载体运输硫胺素单磷酸：硫胺素传递进入哺乳动物细胞的另一种途径。

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摘要

Although the reduced folate carrier RFC1 and the thiamine transporters THTR-1 and THTR-2 share approximately 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 approximately 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.
机译：尽管还原的叶酸载体RFC1和硫胺素转运蛋白THTR-1和THTR-2在蛋白质序列中具有大约40％的同一性，但RFC1不转运硫胺素，THTR-1和THTR-2不转运叶酸。在本研究中，我们证明了硫磷单磷酸（TMP）是血浆和脑脊髓液中存在的重要硫胺素代谢产物的运输，是由RFC1在L1210鼠白血病细胞中介导的。在过表达RFC1的细胞（R16）中，TMP的转运增加了五倍，并被甲氨蝶呤（一种RFC1底物）显着抑制，但未被硫胺素抑制。在接近生理浓度（50 nM）时，RFC1在野生型L1210细胞中介导的TMP流入量约为硫胺素转运蛋白介导的硫胺素流入量的50％。在1分钟内，转运到R16细胞中的大多数TMP被水解为硫胺素，其成分被代谢为硫胺素焦磷酸（活性酶辅因子）。这些数据表明，当在常染色体隐性遗传障碍硫胺素反应性巨幼细胞性贫血中THTR-1发生突变时，RFC1可能是一些组织中TMP可用的替代运输途径之一。

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