SIDEROSIS: CHELATION THERAPY AND MECHANISM

  • Pollack, Simeon, (PI)

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date12/1/781/31/91

ASJC

  • Medicine(all)