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Search For Iron Transport Mechanism Leads To "Hephaestus," God Of Metal Working,Who Insight Into Iron-Deficiency Anemia

Hephaestus, the Greek god of metal-working, wove a net of iron, and ensnared the illicit lovers Ares and Aphrodite making love. Now, centuries later, a newly discovered protein that bears his name is playing an equally revelatory role, exposing an intimate relationship between copper and iron metabolism, and offering researchers an important insight into a cause of iron-deficiency anemia.

The discovery of the Hephaestin gene -- and the protein it encodes -- was made by a team led by researchers at UC San Francisco, in a laboratory high on the hill of San Francisco's Mt. Parnassus.

It is reported in the February issue of Nature Genetics.

The researchers discovered the Hephaestus gene in mice with iron deficiency anemia, and determined that the protein facilitates transport of iron from the intestines into the body's circulatory system. When the gene is mutated, as it is in the mice, iron cannot be transported to the blood, and iron-deficiency anemia occurs.

A like gene exists in humans, thereby offering insight into a condition that affects as much as 25 percent of the world's population.

More broadly, the discovery of Hephaestus offers insight into the overall pathway of iron transport, which follows an intricate three-step path in the body, moving from the intestines through to the circulatory system. A greater understanding of the pathway could shed light on the numerous clinical problems that can develop as a result of iron overload, as well as iron deficiency. Also, the discovery could solve a conundrum that has long puzzled researchers: why supplements of copper, as well as iron, are required to reverse iron-deficiency anemia.

The hephaestin gene, the researchers discovered, produces a copper-bound protein with enzymatic activity that is able to change the valence of iron from its armored state in what is called "iron 2" to its bioavailable state of "iron 3" thereby making available to the body a metal that the ancient Greeks so
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Contact: Jennifer O'Brien
jobrien@itsa.ucsf.edu
415-476-2557
University of California - San Francisco
1-Feb-1999


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