Regulation of Mammalian Iron Metabolism: Current State and Need for Further Knowledge

Abstract

Due to its character as an essential element for all forms of life, the biochemistry and physiology of iron has attracted very intensive interest for many decades. In more recent years, the ways that iron metabolism is regulated in mammalian and human organisms have been clarified, and many aspects of iron metabolism have been reviewed. In this article, some newer aspects concerning absorption and intracellular regulation of iron concentration are considered. These include a sorting of possible models for intestinal iron absorption, a description of ways for membrane passage of iron after release from transferrin during receptor-mediated endocytosis, a consideration of possible mechanisms for non-transferrin bound iron uptake and its regulation, and a review of recent knowledge on the properties of iron regulatory proteins and on regulation of iron metabolism by these proteins, changes of their own properties by non-iron-mediated influences, and regulatory events not mediated by these proteins. This somewhat heterogeneous collection of themes is a consequence of the intention to avoid repetition of the many aforementioned reviews already existing and to concentrate on newer findings generated within the last couple of years.

Human Cytoplasmic Aconitase (Iron Regulatory Protein 1) Is Converted into Its [3Fe-4S] Form by Hydrogen Peroxide in Vitro but Is Not Activated for Iron-responsive Element Binding

“…Bacteria Can Produce Active Human cAcn-The occurrence and function of iron regulatory proteins have so far only been described for metazoans (2,31), although the presence of mRNA sequences resembling IRE has been noticed in bacteria (46). No binding of proteins from E. coli to the human H-ferritin IRE has been evidenced under our experimental conditions.…”

“…Superoxide Inactivates cAcn-In addition to switch activities as a function of the intracellular iron concentration, IRP1 has been shown to respond to a variety of cellular conditions, many of them contributed by ROS and referred to as oxidative stress (2,(31)(32)(33). In contrast to many other Fe-S proteins (34), the aconitase activity of rhIRP1 was insensitive to exposure of the enzyme in air for more than 90 min.…”