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FP5

NUTRIENT IRON TOXICI Informe resumido

Project ID: QLK1-CT-2002-00444
Financiado con arreglo a: FP5-LIFE QUALITY
País: United Kingdom

Identification of an intestinal haem transporter

Absorption of nutrient iron is of key importance for iron metabolism and developmen of both iron deficiency and iron overload. We have identified some iron transport proteins of intestinal mucosal cells. In this project we investigated molecular and functional roles of duodenal cytochrome B (dcytb) in iron metabolism. Most important, however, was the identification of the molecule that transports heme.

Dietary heme iron is an important nutritional source of iron in carnivores and omnivores that is more readily absorbed than non-heme iron derived from vegetables and grain. Most heme is absorbed in the proximal intestine with absorptive capacity decreasing distally. We utilised a subtractive hybridization approach to isolate a heme transporter from duodenum by taking advantage of the intestinal gradient for heme absorption. Here we show a membrane protein named HCP1 (heme carrier protein 1), with homology to bacterial metal-tetracycline transporters, mediates heme uptake by cells in a temperature dependent and saturable manner. HCP1 mRNA was highly expressed in duodenum and regulated by hypoxia. HCP1 protein was iron-regulated and localised to the brush-border membrane of duodenal enterocytes in iron deficiency. Our data indicate that HCP1 is the long sought intestinal heme transporter.

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Contacto

Andrew T. MCKIE, (Senior Lecturer)
Tel.: +44-207-8484509
Fax: +44-207-8484055
Correo electrónico
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