Tfr

[Fe-transferrin]

[utilization Sites]

FIGURE 10 Model for the absorption of iron by the small intestine. TFR, transferrin receptor.

in the form of bone, and calcium ions are essential as second messengers and metabolic regulators as well as for the excitation process of skeletal and cardiac muscle.

Calcium absorption is regulated by vitamin D and parathyroid hormone and is matched to the dietary intake, urinary excretion, and plasma levels of the ion. The regulation of calcium homeostasis and the mechanisms involved are covered in detail in Chapter 43.

Iron

Iron is necessary for the synthesis of hemoglobin, myoglobin, the cytochromes, catalase, and peroxidase. Thus, it plays an essential role in oxygen storage, transfer, and metabolism.

The total body content of iron in the normal adult is only about 4 g, of which approximately 65% is in the form of hemoglobin, 5% is in the form of myoglobin, and 1% is incorporated in enzymes; the remainder is stored in the forms of ferritin and hemosiderin, primarily in the liver. The dietary intake of iron in developed nations is approximately 20 mg/day, derived primarily from the ingestion of meat. Only a small fraction of this daily intake is absorbed, and this appears to be determined, in part, by the bodily needs for this mineral. Thus, the normal adult male absorbs approximately

1 mg/day, and this is sufficient to balance the losses of iron resulting from desquamation of epidermal and intestinal epithelial cells. Growing children and preme-nopausal adult women must absorb approximately

2 mg/day to meet their bodily needs. Iron deficiency resulting from inadequate dietary intake or impaired absorption is one of the most common causes of anemia in the world today.

Iron is absorbed primarily in the duodenum and upper jejunum. As the result of digestive processes, the iron in the luminal contents of these segments is in two forms. The first is iron bound to hemoglobin and myoglobin referred to as ''heme iron.'' The second is free, ionized iron in the ferric (Fe3+) or ferrous (Fe2+) forms.

The cellular mechanisms responsible for the absorption of these two forms are incompletely understood, but a reasonable model is presented in Fig. 10. Heme iron is relatively well absorbed, probably by binding to a putative heme receptor. Some heme may cross the membrane directly because of its lipophilic nature. Within the cell, heme is bound to heme oxygenase and free iron is released. The iron then associates with ferritin and is transported to the basolateral surface. The mechanism by which free iron, primarily in the ferrous (Fe2+) form, enters the cell across the apical membrane is conjectural, but undoubtedly involves binding to a specific protein or carrier. Almost all absorption of nonheme iron takes place in the duodenum.

Free or ionized iron is cytotoxic. Thus, most of the iron in the enterocyte is bound either to a storage protein called apoferritin to form ferritin or to a protein that is responsible for transporting iron through the cytoplasm from the entry step at the apical membrane to the exit step at the basolateral membrane. This protein is often referred to as intestinal transferrin. After exiting the cell, by a mechanism that is not well defined but probably involves recognition by a transferrin receptor, iron is found in the plasma bound to a ^-globulin called transferrin, which, as the name implies, is responsible for transporting or transferring iron from the small intestine to storage sites and from storage sites to sites of use such as the bone marrow. This protein is different from intestinal transferrin. Iron exists within the storage sites, mainly the liver, in the form of ferritin, which, as in the small intestine, appears to be in dynamic equilibrium with iron bound to transferrin.

The prevalent view regarding the regulation of iron absorption by the small intestine is the notion of ''mucosal block.'' According to this notion, iron uptake across the apical membrane is limited by the ability of intestinal transferrin to bind it. When apoferritin in the storage organs and transferrin in the plasma are fully saturated, exit of iron across the basolateral membrane is impeded, leading to saturation of apoferritin and intestinal transferrin in the enterocyte and, in turn, inhibition of further iron uptake across the apical membrane. Conversely, when body iron stores are reduced (e.g., after hemorrhage), apoferritins and trans-ferrins are unsaturated and iron uptake can proceed until these stores are replete.

Suggested Readings

Alpers DH. Digestion and absorption of carbohydrates and proteins.

In Johnson LR, ed. Physiology of the gastrointestinal tract, 3rd ed.

New York: Raven Press, 1994, pp 1723-1750.

Ganapathy V, Brandsch M, Leibach FH. Intestinal transport of amino acids and peptides. In Johnson LR, ed. Physiology of the gastrointestinal tract, 3rd ed. New York: Raven Press, 1994, pp 1773-1794.

Madara L, Trier JS. Functional morphology of the mucosa of the small intestine. In Johnson LR, ed. Physiology of the gastrointestinal tract, 3rd ed. New York: Raven Press, 1994, pp 1577-1622.

Rose RC. Intestinal absorption of water-soluble vitamins. In Johnson LR, ed. Physiology of the gastrointestinal tract, 2nd ed. New York: Raven Press, 1987, pp 1581-1596.

Tso P. Intestinal lipid absorption. In Johnson LR, ed. Physiology of the gastrointestinal tract, 3rd ed. New York: Raven Press, 1994, pp 1867-1908.

Wright EM, Hirayama BA, Loo BBF, et al. Intestinal sugar transport. In Johnson LR, ed. Physiology of the gastrointestinal tract, 3rd ed. New York: Raven Press, 1994, pp 1751-1772.

Wright RM, Turk E, Martin MG. Molecular basis for glucose-galactose malabsorption. Cell Biochem Biophys 2002;36:115-121.

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