The long-term objective of this research is a better understanding of the molecular mechanism and regulatory processes involved in dietary iron absorption and in iron mobilization from tissue stores. Disorders in iron metabolism in humans range from severe deficiency to dangerous excess. It is hoped that studies such as the ones in this proposal will provide insight into the molecular bases of metabolic disorders such as iron deficiency anemia, one of the most common deficiency states in humans, and hemochromatosis, the excess storage of iron, which will permit the development of rational and effective treatments for these disorders. The specific objectives of this study are to determine, on a molecular level, how the mucosal cell very rapidly adjusts to decreases in the iron content of the diet to facilitate the absorption of a greater fraction of dietary iron and to attempt to determine the molecular bases for the impairment of iron absorption observed in riboflavin deficiency. Molecular components implicated to date tin the regulation of both the uptake and processing of iron by the intestinal mucosal cell will be analyzed in laboratory rats raised or transferred to riboflavin-deficient diets. These studies should permit an evaluation of the speed and relative regulatory importance of the two major adjustments in mucosal behavior that have been observed in response to changes in dietary iron content and the identification of defects in these processes that result form riboflavin deficiency. In addition to these animal studies, the two iron-binding components recently identified in extracts of brush-border membrane vesicles will be purified on a large scale and characterized. The mucosal NADH-FMN dependent ferri-reductase that actively promotes the reductive releaser of iron from ferritin will be purified and chemically and kinetically characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK038313-03
Application #
3237610
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1988-05-01
Project End
1993-04-30
Budget Start
1990-05-01
Budget End
1991-04-30
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Richmond
Department
Type
Schools of Arts and Sciences
DUNS #
056915069
City
Richmond
State
VA
Country
United States
Zip Code
23173
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