Protonengekoppelter Folattransporter

Protonengekoppelter Folattransporter
Eigenschaften des menschlichen Proteins
Masse/Länge Primärstruktur 459 Aminosäuren
Isoformen 2
Bezeichner
Gen-Name SLC46A1
Externe IDs
Transporter-Klassifikation
TCDB 2.A.1.50.1
Bezeichnung Major-Facilitator-Superfamilie
Vorkommen
Homologie-Familie Häm-Carrier
Übergeordnetes Taxon Chordatiere

Der protonengekoppelte Folattransporter (PCFT) (auch Häm-Carrier) ist ein Protein, das in der Zellwand von Zellen der Chordatiere zu finden ist. Es erleichtert den Zufluss von Folsäure und Häm ins Zellinnere (Zytosol). Es handelt sich daher um ein Transportprotein. Beim Menschen ist PCFT hauptsächlich in Nieren, Leber, Plazenta, Dünndarm, Milz und Netzhaut lokalisiert. Mutationen im SLC46A1-Gen können zu Transportermangel und dieser zur (seltenen) erblichen Folsäure-Malabsorption führen.[1]

Häm in Nahrungsmitteln ist eine wichtige Quelle für Eisen. Bei Eisenüberschuss im Körper wird PCFT in Darmzellen von der apikalen Seite der Membran ins Zytosol verfrachtet; der umgekehrte Prozess findet bei Eisenmangel statt. In der Zelle wird das Eisen vom Porphyrin befreit und ins Blutplasma transportiert.[1]

Folatüberschuss führte in Zellkulturen zu einem signifikanten Rückgang der Expression aller folattransportierenden Proteine (PCFT, RFC, Folatrezeptor) in Darmzellen.[2]

Das Antifolat Permetrexed wird von PCFT transportiert. Ähnlich wie bei Ferroportin wird die Produktion von PCFT in Makrophagen bei Entzündungsgeschehen herunterreguliert. Dexamethason aktiviert die Expression.[3][4]

Der katalysierte Membrantransport von PCFT:[5]

Substrat (außen) + H+ (außen)    Substrat (innen) + H+ (innen)

Es handelt sich also um einen Symport. Die Affinität gegenüber Folat als Substrat ist größer als zu Häm. Der Arbeitsbereich für den Folsäuretransport liegt bei pH 4,0 bis 5,5.[1]

Einzelnachweise

  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. Jahrgang, Nr. 1, Juli 2007, S. 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. Jahrgang, Nr. 3, September 2008, S. 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. Jahrgang, Nr. 2, Februar 2008, S. 325–33, doi:10.1189/jlb.0407226, PMID 17947394.
  5. ↑ TCDB 2.A.1

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