Identification of Proton-Coupled High-Affinity Human Intestinal Folate Transporter Mutated in Human Hereditary Familial Folate Malabsorption

Abstract

The human folate transporter of the small intestine has been identified and characterized. It functions optimally at the low pH (6.0-6.2) characteristic of the microenvironment of the duodenal brush border membrane, where dietary folates are mainly absorbed. The transporter, named PCFT/HCP1, is a protein of approximately 50 kDa and functions as a reversible, electrogenic, proton-coupled high-affinity folate transporter (PCFT). It shows high specificity for folates and anti-folates. This protein was previously identified as an intestinal heme carrier protein HCP1. Patients suffering from hereditary familial folate malabsorption were found to be homozygous for a mutation of the PCFT/HCP1 gene due to loss of a particular exon coding for 28 amino acids.