Sanyal A J, Hirsch J I, Moore E W
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University.
J Lab Clin Med. 1990 Jul;116(1):76-86.
Two of the major divalent cations in human physiology, Ca++ and Fe++, are poorly soluble at the pH of intestinal contents, and active "uphill" transport mechanisms exist for both ions in proximal small intestine. We have recently demonstrated significant binding of Ca++ to both premicellar and micellar bile salts and have postulated that high-affinity premicellar binding involves interposition of Ca++ between terminal carboxyl (COO-) and 7-OH or 12-OH groups of the steroid ring. The present studies were made to determine whether such binding extends to other divalent cations, and specifically to Fe++, which, like Ca++, has a hydrated diameter of 6 A. Equilibrium dialysis studies of sodium taurocholate were made at 25 degrees C with solutions containing 0.5 to 150 mmol/L taurocholate and 0.018 to 1.8 mmol/L iron 59-labeled FeSO4 at pH 3.0 to 6.3 and a total ionic strength of 0.15 mol/L. In control (saline dialysand) cells, [Fe++] was virtually equal in dialysands and dialysates within 5 hours. In sharp contrast, taurocholate-containing dialysands showed significantly higher counts than dialysates, indicating Fe++ binding to taurocholate, independent of pH and Fe concentration. After correction for taurocholate-induced Gibbs-Donnan effects across the membrane, the apparent taurocholate affinity constant (K'f) for Fe++ in micellar solutions (5 to 150 mmol/L) was essentially constant at about 3.1 (mol/L)-1, then increased dramatically below the critical micellar concentration to greater than 100 (mol/L)-1 at [taurocholate] = 0.5 mmol/L. The hyperbolic rise in K'f below the critical micellar concentration is similar to that which we have previously reported for Ca++, indicating significant high-affinity binding of Fe++ to premicellar taurocholate anions and low-affinity binding to micellar anions. It is postulated that Fe++ binding, particularly by premicellar bile salts, may play an important physiologic role in increasing iron solubility within the intestinal lumen, thus increasing iron absorption. The possible role of bile salts in increasing divalent cation solubility and absorption from the intestine is a new field of bile acid research.
人体生理学中的两种主要二价阳离子，即Ca++和Fe++，在肠内容物的pH值下溶解度很低，并且在近端小肠中这两种离子都存在活跃的“上坡”转运机制。我们最近证明了Ca++与前胶束和胶束胆盐都有显著结合，并推测高亲和力的前胶束结合涉及Ca++插入类固醇环末端羧基（COO-）与7-OH或12-OH基团之间。本研究旨在确定这种结合是否扩展到其他二价阳离子，特别是Fe++，它与Ca++一样，水合直径为6 Å。在25℃下，用含有0.5至150 mmol/L牛磺胆酸钠和0.018至1.8 mmol/L铁59标记的FeSO4、pH值为3.0至6.3且总离子强度为0.15 mol/L的溶液进行牛磺胆酸钠的平衡透析研究。在对照（生理盐水透析液）细胞中，5小时内透析液和透析外液中的[Fe++]实际上相等。形成鲜明对比的是，含有牛磺胆酸钠的透析液显示出的计数明显高于透析外液，表明Fe++与牛磺胆酸钠结合，与pH值和铁浓度无关。校正跨膜的牛磺胆酸钠诱导的吉布斯-唐南效应后，胶束溶液（5至150 mmol/L）中Fe++的表观牛磺胆酸钠亲和常数（K'f）在约3.1（mol/L）-1基本恒定，然后在低于临界胶束浓度时急剧增加，在[牛磺胆酸钠] = 0.5 mmol/L时大于100（mol/L）-1。低于临界胶束浓度时K'f的双曲线上升与我们之前报道的Ca++相似，表明Fe++与前胶束牛磺胆酸根阴离子有显著的高亲和力结合，与胶束阴离子有低亲和力结合。据推测，Fe++结合，特别是前胶束胆盐的结合，可能在增加肠腔内铁的溶解度从而增加铁吸收方面发挥重要生理作用。胆盐在增加二价阳离子溶解度和从肠道吸收方面的可能作用是胆汁酸研究的一个新领域。
