Identification of an Intestinal Folate Transporter and the Molecular Basis for Hereditary Folate Malabsorption

Andong Qiu, Michaela Jansen, Antoinette Sakaris, Sang Hee Min, Shrikanta Chattopadhyay, Eugenia Tsai, Claudio Sandoval, Rongbao Zhao, Myles H. Akabas, I. David Goldman

Research output: Contribution to journalArticle

571 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)917-928
Number of pages12
JournalCell
Volume127
Issue number5
DOIs
StatePublished - Dec 1 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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