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The dog behaves like man in his ability to utilize dietary hemoglobin iron and, therefore, is an excellent model in which to study the mechanisms of absorption. Heme is taken up intact into the epithelial cell of the small intestine but the iron appears in the plasma in a nonheme form. A substance is present in mucosal homogenates which is capable of releasing iron from a hemoglobin substrate in vitro. This has a molecular weight greater than 64,000, and appears to behave as an enzyme. There is no difference in the in vitro, effective concentration of the hemesplitting substance in the mucosa of iron-loaded and iron-deficient dogs to explain in vivo changes in iron absorption. However, the rate at which the heme-splitting substance works in vivo appears to be increased by the removal of the nonheme-iron-end product from the epithelial cell to the plasma. Reduction of the heme-iron content within the epithelial cell may then enhance uptake from the lumen. These studies suggest that the labile nonheme-iron content of the intestinal epithelial cell determines its ability to accept heme as well as ionized iron from the lumen.

Absorption of hemoglobin iron: the role of a heme-splitting substance in the intestinal mucosa