Proton-coupled folate transporter

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Proton-coupled folate transporter
Properties of human protein
Mass / length primary structure 459 amino acids
Isoforms 2
Identifier
Gene name SLC46A1
External IDs
Transporter classification
TCDB 2.A.1.50.1
designation Major Facilitator Super Family
Occurrence
Homology family Heme carriers
Parent taxon Chordates

The proton-coupled folate transporter (PCFT) (also heme carrier ) is a protein that can be found in the cell wall of cells of the chordates . It facilitates the inflow of folic acid and heme into the cell interior ( cytosol ). It is therefore a transport protein . In humans, PCFT is mainly localized in the kidneys , liver , placenta , small intestine , spleen and retina . Mutations in the SLC46A1 - gene can transporter deficiency and this hereditary to the (rare) folate malabsorption lead.

Heme in food is an important source of iron . If there is an excess of iron in the body, PCFT is transported in intestinal cells from the apical side of the membrane into the cytosol; the reverse process takes place in the case of iron deficiency. In the cell, the iron is freed from the porphyrin and transported into the blood plasma.

In cell cultures, excess folate led to a significant decrease in the expression of all folate-transporting proteins (PCFT, RFC , folate receptor ) in intestinal cells.

The antifolate Permetrexed is transported by PCFT. Similar to ferroportin , the production of PCFT in macrophages is downregulated during inflammation . Dexamethasone activates expression.

The catalyzed membrane transport of PCFT:

Substrate (outside) + H + (outside)     substrate (inside) + H + (inside)

So it is a symport . The affinity for folate as a substrate is greater than for heme. The working range for folic acid transport is pH 4.0 to 5.5.

Individual evidence

  1. ↑ a b c UniProt Q96NT5
  2. ↑ Ashokkumar B, Mohammed ZM, Vaziri ND, Said HM: Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells . In: Am. J. Clin. Nutr. . 86, No. 1, July 2007, pp. 159-66. PMID 17616776 .
  3. ↑ Zhao R, Qiu A, Tsai E, Jansen M, Akabas MH, Goldman ID: The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier . In: Mol. Pharmacol. . 74, No. 3, September 2008, pp. 854-62. doi : 10.1124 / mol.108.045443 . PMID 18524888 .
  4. ↑ Schaer CA, Vallelian F, Imhof A, Schoedon G, Schaer DJ: Heme carrier protein (HCP-1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation . In: J. Leukoc. Biol . 83, No. 2, February 2008, pp. 325-33. doi : 10.1189 / jlb.0407226 . PMID 17947394 .
  5. ↑ TCDB 2.A.1

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