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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL021560-07
Application #
3336563
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1978-12-01
Project End
1991-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Weaver, J; Zhan, H; Pollack, S (1993) Erythrocyte haemolysate interacts with ATP-Fe to form a complex containing iron, ATP and 13 800 MW polypeptide. Br J Haematol 83:138-44
Pollack, S (1992) Receptor-mediated iron uptake and intracellular iron transport. Am J Hematol 39:113-8
Zhan, H; Gupta, R K; Weaver, J et al. (1990) Iron bound to low MW ligands: interactions with mitochondria and cytosolic proteins. Eur J Haematol 44:125-31
Weaver, J; Pollack, S (1990) Iron binding to apotransferrin. Acta Haematol 84:68-71
Weaver, J; Zhan, H; Pollack, S (1990) Mitochondria have Fe(III) receptors. Biochem J 265:415-9
Jelicks, L A; Weaver, J; Pollack, S et al. (1989) NMR studies of intracellular free calcium, free magnesium and sodium in the guinea pig reticulocyte and mature red cell. Biochim Biophys Acta 1012:261-6
Zhan, H; Pollack, S; Weaver, J (1989) Hemolysates reduce iron released from transferrin. Am J Hematol 31:203-7
Pollack, S (1989) P. falciparum iron metabolism. Prog Clin Biol Res 313:151-61
Weaver, J; Pollack, S; Zhan, H (1989) Low molecular weight iron from guinea pig reticulocytes isolated by Sephadex G-25 chromatography. Eur J Haematol 43:321-7
Pollack, S; Schnelle, V (1988) Inability to detect transferrin receptors on P. falciparum parasitized red cells. Br J Haematol 68:125-9

Showing the most recent 10 out of 14 publications