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Nutrition Biochemist Explores Iron Uptake in the Body
Marianne Wessling-Resnick, associate professor of nutrition, is preoccupied with iron. Specifically, she wants to understand the
mechanisms by which cells absorb iron.
"Iron is a toxic mineral," said Wessling-Resnick. "Yet it's essential to life. Most of the dietary iron a person ingests is absorbed into hemoglobin, which delivers oxygen to the body's cells."
The amount of iron absorbed by the body must be carefully regulated and held in balance. Too little iron produces anemia, a condition that affects approximately half of the world's population. Too much of it produces iron toxicity, which leads to cirrhosis of the liver, hepatic carcinoma, congestive heart failure, and other health problems.
The puzzle that Wessling-Resnick is trying to solve is what are the mechanisms that, for most people, maintain a healthy balance between the amount of iron absorbed and the body's iron requirements.
"In most people," said Wessling-Resnick, "About ten percent of the dietary iron is absorbed. We've found that the cells can regulate how much or how little iron they absorb. What we want to know is, what stimulates a cell to increase or decrease its iron absorption?"
The path to the answer, Wessling-Resnick believes, lies in understanding the iron-absorption mechanism. Previous research has shown that iron is bound by a serum protein called transferin and is then able to pass through the walls of cells, where it is released and put to use by the body. The component of this process that hasn't been understood is the process by which iron is able to pass through cell membranes.
Wessling-Resnick yearned to understand this process. She conceived of an experimental approach called functional expression cloning that would identify the proteins responsible for iron transport. This method used immature frog oocytes, which were injected with cRNA, copied from a DNA library, that would encode proteins that could support iron uptake. The oocytes were tested for ability to absorb iron and, if positive, the results would indicate that the critical factor was present.
A diagram of the SFT protein identified by Marianne Wessling-Resnick
Once iron-transporting oocytes were found, it was possible to
identify the specific protein responsible for transporting iron across
cell membranes. Wessling-Resnick has named this protein SFT, for
Stimulater of Fe Transport.
Identifying the SFT protein was a giant step forward in understanding the iron-absorption process, yet is just one step along the journey. It may, however, provide a foundation for devising new therapies for the large populations suffering from anemia.
"The large numbers of anemia cases stem from a variety of causes," said Wessling-Resnick. "In addition to iron-deficient diets, there are folate deficiencies and parasitic diseases, like malaria, which cause people to bleed. If we were somehow able to increase the activity of the SFT protein, we might be able to help a great number of people."
On the other side of the iron spectrum are those with overloads of iron. While iron toxicity can be caused by megadosing on iron supplements, it is more often the result of a genetic defect called hemochromatosis. This disease affects one in four hundred Americans. In hemochromatosis suffers, iron builds up in the soft tissues of the body, particularly the liver. Because it takes a large concentration of iron to cause symptoms, most people with this disease don't present with symptoms until they are in their 30s or older.
Marianne Wessling-Resnick, associate professor of nutrition
There are unfortunate side effects of late presentation of
hemochro-motosis symptoms. One is that the damage caused by iron toxicity is
irreparable. Further damage can be controlled by phlebotomy
(bleeding), but repair is impossible.
Another consequence is that, by the time a person knows that he or she carries this genetic defect, it may already have been passed on to his or her children. Some physicians have called for routine hemochromatosis screening, so that treatment of affected individuals could begin before damage was incurred.
An important relationship recently discovered by Wessling-Resnick's laboratory is that unusually high levels of SFT are found in the liver of patients with hemochromatosis. Whether SFT contributes to the etiology of the disease is unknown.
Wessling-Resnick will continue to progress towards
understanding iron-absorption mechanisms. When asked whether she might find the
answers to all of her iron-intake questions, she laughed: "There's a
lot here to learn. This will occupy me for a long, long time."
