Several previous studies have shown that whole bile and/or bile salts enhance absorption of both iron and calcium. The purposes of this proposal is: (1) to define and quantify binding of Fe++ and Fe+++ to specific bile salts, and (2) to define and quantify the effects of these bile salts on the absorption of ionic calcium (Ca++) and iron (Fe++ and Fe+++) from each region of the small intestine. Of the 3 major divalent cations in human physiology: Ca++, Fe++, and Mg++, only Mg++ is freely soluble at the pH of intestinal contents. Thus, upon entry of acid gastric contents into the alkaline duodenum, the solubility of each ion is governed by the least soluble species present. For calcium, this is CaC03, and for iron it is Fe(OH)3 or Fe203. One major cation thus forms chalk, and the other forms rust, both of which are virtually insoluble. Nature has combatted these severe solubility limitations by specific active carrier-mediated transport mechanisms in the mucosal cell, particularly in the proximal intestine. Another factor of potential importance is the presence of intraluminal macromolecules with calcium-binding and iron- binding properties which could substantially increase the solubility of the respective ions. The present proposal was prompted by our recent observations that certain monomeric bile salts show significant high-affinity Ca++ binding properties. The present proposal will test the hypothesis that bile salts are also important buffers for Ca++, F++ and Fe+++ ions in the small intestine. Our hypothesis is that bile salt monomers, by virtue of high-affinity binding of both Ca++ and Fe++ (and possibly Fe+++), play an important role in enhancing the intestinal absorption of these ions. Such binding could substantially increase the soluble ionic pools and thus increase delivery of the ions to the mucosal membrane. For the first time, in vitro studies will assess binding of both ferrous (Fe++) and Ferric (Fe+++) ions to bile salts, and define structural requirements for this binding. The effects of various bile salts having specific structural properties will be used to define and quantify effects on Ca++, Fe++ and Fe+++ transport using: (1) Everted rat gut sacs in vitro, and (2) Isolated rat intestinal segments in vivo. Studies are also proposed to determine possible enhancement of ileal Ca++, Fe++ and Fe++ absorption by bile salt transport.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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General Medicine A Subcommittee 2 (GMA)
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Virginia Commonwealth University
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