We do not know how iron is transported between transferrin, ferritin and heme. Though low molecular weight forms of iron have been suspected to be transport intermediaries, their isolation and characterization has been elusive. We have isolated, purified and characterized a nucleotide-iron complex from a low molecular weight fraction obtained from reticulocyte hemolysate. This fraction was among the earliest to bind 59Fe when reticulocytes were incubated with 59Fe serum, and among the first to lose its 59Fe following a pulse chase. The iron nucleotide complex contains adenine, or a closely related base; its ribose to P ratio is 1:1. In this proposal we outline the further study of this low molecular weight iron nucleotide complex, including its interaction with transferrin and ferritin, and the efficiency with which it donates iron for heme synthesis. The interactions of the low molecular weight iron nucleotide complex with cofactors is also suggested, and these interactions are also to be studied. The studies have the long term goal of identifying the components and pathways involved in intracellular iron transport. Diseases in which excess iron is responsible for tissue damage, including Thalassemia major and hemochromatosis, may yield to better management by virtue of the insights provided by this work. Also, a variety of important biologic processes are dependent on intracellular iron transport including DNA and collagen synthesis, and the many diseases in which these may be impaired or disordered may benefit by the insights provided by this work.
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