BCS 301/401/402 Research
Dr. Bailey

The Mechanism of Chelator-Mediated
Iron-Release From Transferrin.



The transferrins are a class of iron-binding proteins (MW approx. 80kDa) whose function is to transport iron in the body. They may also act as iron-buffers and as antimicrobial agents.

Transferrin normally keeps the amount of free iron in the blood low, however it can become saturated. This condition is particularly acute with certain blood disorders, such as the thallasemias, which require frequent whole blood transfusions. Because there is no physiological mechanism for the removal of excess iron in the body, a toxic buildup results, eventually resulting in organ failure and death.

Attempts to remove excess iron from the body have centered on iron-chelating agents (small molecules which can envelop iron atoms). Irreversibly removing iron from transferrin will allow the protein's natural buffering action to remove excess iron from other areas of the body. The chelated iron may be successfully excreted. Unfortunately, the chelator presently being used clinically, Desferrioxamine B, is both kinetically slow and orally inactive. An understanding of the mechanism by which chelators remove iron from transferrin is vital to the development and testing of new more effective clinical chelators.

One of the unique features of the transferrins is that in order for iron to bind a suitable synergistic anion must also be present. Loss of this anion has been implicated as an important step in iron release. We are examining the effect of a covalently bound synergistic anion (an affinity label) on chelator-mediated iron-release from transferrin in an attempt to further discern the mechanism of this process. Our results confirm the presence of two pathways for iron-release: one that is hyperbolic in nature and second that is first-order in nature. The affinity-label appears to shut off the latter pathway.

Portions of this work have been published. See: Bailey, et al., BIOCHEMISTRY, 36, 10105-10108 (1997).

See the article about some of the students who have been involved in this research in the Wells College Express.

What you might learn:

Protein handling; affinity-labeling techniques; spectroscopic data acquisition; kinetic analysis.

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