Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption
Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption
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DOI：
10.1016/j.cell.2006.09.041
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发表时间：
2006-12-01
期刊：
影响因子：
64.5
通讯作者：
Goldman, I. David
中科院分区：
文献类型：
--
作者：
Qiu, Andong;Jansen, Michaela;Goldman, I. David
叶酸是单碳生物合成和表观遗传过程所必需的营养物质。虽然叶酸在小肠上部的酸性环境中被吸收，但其潜在的吸收机制尚未明确。我们现在报道了一种人类质子偶联的高亲和力叶酸转运蛋白的鉴定，该转运蛋白概括了叶酸在肠道和低ph下各种细胞类型中运输和吸收的特性。我们证明了该基因的功能缺失突变是该疾病家族中遗传性叶酸吸收不良的分子基础。这种转运蛋白以前被报道为一种低亲和力、不依赖ph值的血红素载体蛋白HCP1。然而，目前的研究表明，该基因产物的主要功能是人体叶酸稳态所需的质子偶联叶酸运输，因此我们将其名称修改为PCFT/HCP1。
Folates are essential nutrients that are required for one-carbon biosynthetic and epigenetic processes. While folates are absorbed in the acidic milieu of the upper small intestine, the underlying absorption mechanism has not been defined. We now report the identification of a human proton-coupled, high-affinity folate transporter that recapitulates properties of folate transport and absorption in intestine and in various cell types at low pH. We demonstrate that a loss-of-function mutation in this gene is the molecular basis for hereditary folate malabsorption in a family with this disease. This transporter was previously reported to be a lower-affinity, pH-independent heme carrier protein, HCP1. However, the current study establishes that a major function of this gene product is proton-coupled folate transport required for folate homeostasis in man, and we have thus amended the name to PCFT/HCP1.