Qiu Andong, Jansen Michaela, Sakaris Antoinette, Min Sang Hee, Chattopadhyay Shrikanta, Tsai Eugenia, Sandoval Claudio, Zhao Rongbao, Akabas Myles H, Goldman I David
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Cell. 2006 Dec 1;127(5):917-28. doi: 10.1016/j.cell.2006.09.041.
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.
叶酸是一碳生物合成和表观遗传过程所需的必需营养素。虽然叶酸在上段小肠的酸性环境中被吸收，但其潜在的吸收机制尚未明确。我们现在报告鉴定出一种人类质子偶联的高亲和力叶酸转运蛋白，它概括了叶酸在低pH值下在肠道和各种细胞类型中的转运和吸收特性。我们证明，该基因的功能丧失突变是一个患有这种疾病的家族中遗传性叶酸吸收不良的分子基础。该转运蛋白先前被报道为一种低亲和力、不依赖pH值的血红素载体蛋白，即HCP1。然而，目前的研究表明，该基因产物的主要功能是人类叶酸稳态所需的质子偶联叶酸转运，因此我们将其名称修改为PCFT/HCP1。
