Applications of magnetic resonance techniques in the medical sciences have recently proliferated. I propose to undertake, during Phase I, detailed spectroscopic studies of uteroferrin, one of a newly recognized class of proteins with binuclear iron centers, the purple acid phosphatases. Evans magnetic susceptibility measurements will be performed to reconcile and rationalize previous findings concerning a transient phosphate- induced intermediate state of uteroferrin in which the protein exhibits characteristics of both its oxidized, diamagnetic and reduced, paramagnetic forms. Spectroscopic studies will also be performed to obtain information about the ligand structure and charge distribution of uteroferrin's binuclear iron center. The goal is to progress toward a thorough understanding of the chemistry and biological significance of uteroferrin, while acquiring facility with the techniques of magnetic resonance spectroscopy. During Phase II, I will turn to studies of intracellular iron metabolism of relevance to iron associated derangements in the liver, as well as the erythropoietic and immune systems. The experimental system to be studied will be the Kupffer cell of the liver. The hypothesis to be tested is that iron toxicity contributes to the diminished Kupffer cell viability observed after unrestrained erythrophagocytosis by these cells.
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