Functional properties of transfected human DMT1 iron transporter.

Autor: Worthington MT; Digestive Health Research Center, Division of Gastroenterology and Hepatology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908-0708, USA. mtw3p@virginia.edu, Browne L, Battle EH, Luo RQ
Jazyk: angličtina
Zdroj: American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2000 Dec; Vol. 279 (6), pp. G1265-73.
DOI: 10.1152/ajpgi.2000.279.6.G1265
Abstrakt: Recently, mutation of the DMT1 gene has been discovered to cause ineffective intestinal iron uptake and abnormal body iron metabolism in the anemic Belgrade rat and mk mouse. DMT1 transports first-series transition metals, but only iron turns on an inward proton current. The process of iron transport was studied by transfection of human DMT1 into the COS-7 cell line. Native and epitope-tagged human DMT1 led to increased iron uptake. The human gene with the Belgrade rat mutation was found to have one-fifth of the activity of the wild-type protein. The pH optimum of human DMT1 iron uptake was 6.75, which is equivalent to the pH of the duodenal brush border. The transporter demonstrates uptake without saturation from 0 to 50 microM iron, recapitulating earlier studies of isolated intestinal enterocytes. Diethylpyrocarbonate inhibition of iron uptake in DMT1-transfected cells suggests a functional role for histidine residues. Finally, a model is presented that incorporates the selectivity of the DMT1 transporter for transition metals and a potential role for the inward proton current.
Databáze: MEDLINE