EFFECTS OF BILE ACIDS ON CALCIUM AND IRON ABSORPTION

先前的几项研究表明，整个胆汁和/或胆汁 盐能促进铁和钙的吸收。 而言 （1）定义和量化Fe++的结合， Fe+对特定胆汁盐的影响，以及（2）定义和定量 这些胆汁盐对钙离子吸收的影响 (Ca++）和铁（Fe++和Fe+）从每个区域的小 肠子 人体生理学中的三种主要二价阳离子： Ca++、Fe++和Mg++，只有Mg++在pH为 肠内容物 因此，当酸性胃内容物进入 在碱性十二指肠中，每种离子的溶解度由以下因素决定： 最难溶解的物质 对于钙，这是CaCO 3，并且 对于铁，它是Fe（OH）3或Fe 2 O3。 一个主要的阳离子因此形成 粉笔，和其他形式的生锈，这两个几乎都是 不溶的 大自然已经克服了这些严重的溶解性 特异性活性载体介导转运的限制 在粘膜细胞中的机制，特别是在近端 肠子 另一个潜在的重要因素是 与钙结合的管腔内大分子和铁- 结合性能，可以大大增加溶解度 各自的离子。 目前的建议是由我们的 最近的观察表明，某些单体胆汁盐 显著的高亲和力Ca++结合特性。 本 一项提案将检验胆汁盐也很重要的假设 小肠中Ca++、F++和Fe+离子的缓冲液。 我们 假设是胆汁盐单体，由于高亲和力 Ca++和Fe++（可能还有Fe+）的结合， 在增强这些肠道吸收的重要作用 离子。 这种结合可以显著增加可溶性离子的浓度。 从而增加离子向粘膜的输送 膜的 体外研究将首次评估 亚铁（Fe++）和铁（Fe+）离子转化为胆汁盐，以及 定义此绑定的结构要求。 的影响 将使用具有特定结构性质的各种胆汁盐 定义和量化对Ca++、Fe++和Fe+转运的影响 使用：（1）体外外翻大鼠肠囊，和（2）离体大鼠 体内肠段。 还建议进行研究， 确定回肠Ca++、Fe++和Fe++的可能增强 通过胆盐转运吸收。

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.