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 盐可以促进铁和钙的吸收。其目的是 这一建议的目的是：(1)定义和量化Fe++和 Fe+对特定胆盐的影响，以及(2)定义和定量 胆盐对离子钙吸收的影响 (Ca++)和铁(Fe++和Fe+)来自各地区的小 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值下可自由溶解。 肠道内容物。因此，当酸性胃内容物进入 在碱性十二指肠中，每个离子的溶解度受 存在的最难溶的物种。对于钙，这是CaC03，和 对于铁，它是Fe(OH)3或Fe203。这样就形成了一个主要阳离子 粉笔和其他形式的铁锈，这两种形式几乎都是 不解之缘。自然界已经克服了这些严重的溶解性 特定活性载体介导的转运的限制 粘膜细胞，特别是近端粘膜细胞的机制 肠子。另一个潜在的重要因素是 腔内结合钙和铁的大分子- 可显著增加溶解度的结合性能 各自的离子。目前的建议是由我们的 最近的观察表明，某些单体胆盐显示 显著的高亲和力钙离子结合特性。现在 该提案将检验胆盐也很重要这一假设 小肠中钙、氟、铁离子的缓冲液。我们的 假说是，胆盐单体凭借高亲和力 Ca++和Fe++(可能还有Fe+)的结合，发挥了 在促进这些物质的肠道吸收中的重要作用 离子。这种结合可以显著增加可溶性离子。 因此增加了离子向粘膜的输送 薄膜。体外研究将第一次评估结合作用 将亚铁(Fe++)和铁离子(Fe++)两者转化为胆盐，以及 定义此绑定的结构要求。的影响 将使用具有特定结构特性的各种胆盐 确定和量化对Ca++、Fe++和Fe+转运的影响 使用：(1)体外培养的大鼠外翻肠囊；(2)分离的大鼠 活体内的肠段。还建议进行研究，以 确定回肠Ca++、Fe++和Fe++的可能增强 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.