Premicellar taurocholate avidly binds ferrous (Fe++) iron: a potential physiologic role for bile salts in iron...

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.