Consistent discrepancies in the regulation of iron absorption in the proximal small intestine result in either iron deficiency or iron overloading. Regulation is not adequately explained by mucosal transferrin and ferritin. Therefore, we searched for other iron binding proteins in intestinal mucosa. Using physical methods of separation and modern chromatographic methods, we found water- soluble iron binding compounds with approximate molecular sizes of 520,000 and 60,000 daltons which were immunologically distinct from transferrin and ferritin. Since sixty percent of a lumenal dose of radioiron is found in water insoluble fractions of mucosal preparations, this was investigated. Half of the radioiron was bound to mucin and the remainder was isolated in heat stable, triton-100 soluble fractions with molecular sizes of 150,000 daltons and 60,000 daltons on SDS PAGE gels. Observations in rat duodenal mucosa are being extended to human intestinal specimens obtained at surgery and endoscopy. Preliminary observations in human tissues suggest they are similar to findings in rat derived specimens. Animal experiments will be scaled up to yield increased quantities of purified proteins to permit characterization of isolates (amino acid analysis, isoelectric point, sedimentation coefficient, iron content and iron binding affinity). Polyclonal and monoclonal antibodies are being obtained for use in increasing yields of functional protein isolates and to permit quantification of each of the iron binding proteins in intestinal specimens in the various states of iron repletion and in other conditions in which iron absorption is affected. Likewise, this will permit in vitro studies of the affinity of iron for these proteins and the results of inhibition studies using other divalent metal cations which have increased absorption in iron deficiency. The quantity of the iron binding proteins in various portions of the intestine and other body organs will be studied in the various states of iron repletion and in other conditions in which iron absorption is affected to determine whether the regulation of iron absorption is effected by either alterations in the quantity of iron binding substances or by saturating the iron binding sites in these receptors with iron or other metal cations or both. We postulate that characterization of our iron binding isolates and establishment of their relationship to one another and known iron binding proteins will provide a basic understanding of iron absorption.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Hematology Subcommittee 2 (HEM)
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University of South Alabama
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Umbreit, J N; Conrad, M E; Berry, M A et al. (1997) The alternate iron transport pathway: mobilferrin and integrin in reticulocytes. Br J Haematol 96:521-9
Umbreit, J N; Conrad, M E; Moore, E G et al. (1996) Paraferritin: a protein complex with ferrireductase activity is associated with iron absorption in rats. Biochemistry 35:6460-9
Conrad, M E (1995) Bone marrow necrosis. J Intensive Care Med 10:171-8
Conrad, M E; Uzel, C; Berry, M et al. (1994) Ironic catastrophes: one's food--another's poison. Am J Med Sci 307:434-7
Conrad, M E; Umbreit, J N; Moore, E G et al. (1994) Alternate iron transport pathway. Mobilferrin and integrin in K562 cells. J Biol Chem 269:7169-73
Conrad, M E; Umbreit, J N; Moore, E G et al. (1994) Hereditary hemochromatosis: a prevalent disorder of iron metabolism with an elusive etiology. Am J Hematol 47:218-24
Conrad, M E; Umbreit, J N; Peterson, R D et al. (1993) Function of integrin in duodenal mucosal uptake of iron. Blood 81:517-21
Conrad, M E; Umbreit, J N (1993) A concise review: iron absorption--the mucin-mobilferrin-integrin pathway. A competitive pathway for metal absorption. Am J Hematol 42:67-73
Conrad, M E (1993) Excess iron and catastrophic illness. Am J Hematol 43:234-6
Conrad, M E; Umbreit, J N; Moore, E G (1993) Regulation of iron absorption: proteins involved in duodenal mucosal uptake and transport. J Am Coll Nutr 12:720-8

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