Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. 1718 1

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.
 ...
PMID:Identification of proton-coupled high-affinity human intestinal folate transporter mutated in human hereditary familial folate malabsorption. 1823 95