Hemoglobin iron absorption kinetics in the iron-deficient dog

In the absorption of Hb iron (HbFe), heme is separated from globin in the intestinal lumen and enters mucosal cells where Fe is split off and transported to blood. Previous studies indicated that this final step is the limiting one in absorption of HbFe in normal and Fe loaded animals but not in Fe-deficient animals. The present studies were designed to determine the limiting step in absorption of HbFe in Fe-deficient dogs. Varying Amounts of 59Fe labeled Hb were injected into closed duodenal loops in anesthetized dogs. Each step in the absorptive process was measured: intralumenal separation of the heme from Hb; mucosal uptake of heme; intramucosal splitting of Fe from heme; transport of Fe to blood. This process was characterized using a five compartment kinetic model. The resulting seven rate constants were determined to best describe the observed absorption data. Results show: 1) with increasing dose of 59HbFe, mucosal uptake of heme, Fe split from heme in mucosa, and Fe transported to blood all increase linearly. 2) Mucosal 59Fe-heme accumulates over the 3-hour period while 59Fe does not, indicating rapid transport of 59Fe split from heme. These results suggest that the rate limiting step in absorption of HbFe in Fe-deficient dogs is the splitting of Fe from heme in the mucosa.