At the same time, it raised doubts about the current dogma regarding the transferrin cycle, whose discovery constitutes the major advance in the field during the 1980s. A central aspect of iron metabolism, the transferrin cycle begins with the transferrin receptor, a protein found on the surface of many cell types, particularly immature red blood cells. Iron then leaves these vesicles through the transporter Nramp2 and enters mitochondria, which use it to make heme for hemoglobin and generate energy. Advanced Medical Graphics Hoping to better understand disorders of iron metabolism, Nancy Andrews and her colleagues have created several strains of mutated mice that allow them to trace iron s path through the body. Dietary iron enters intestinal cells through the Nramp2 transporter, recently renamed DMT1.
Mitochondria then insert iron into heme, which is later turned into hemoglobin.
The bone marrow somehow signals the intestine to adjust the amount of iron absorbed from food. Of the body s total iron content about 4 grams only 2 milligrams is absorbed from food every day, the remaining 3.998 grams are all reused iron that is recycled through the macrophages in ways not yet understood at a molecular level. In the current study, Andrews and colleagues at Brigham and Women's Hospital tested whether this cycle was the major mechanism to get iron into all cells of the body, by creating mutant mice lacking the transferrin receptor. The results confirmed their hunch that the transferrin cycle instead served the more specialized role of concentrating iron mostly in red blood cells, which need especially large amounts of the metal. Not surprisingly, embryos lacking both copies of the gene died in utero of severe anemia.