ABSTRACT
Introduction 421
Dietary Iron Absorption 422
Iron-Dependent Regulation of Intestinal Iron Absorption 423
Iron Regulatory Proteins 424
Iron Responsive Elements 424
Regulation of DMT1 426
Regulation of IREG1 426
Regulation of Dcytb and Hephaestin 427
Hypoxia 427
The Role of Hepcidin in Regulating Body Iron Metabolism 428
Hemochromatosis 430
Iron: A Pro-oxidant 432
Conclusions 433
References 433
INTRODUCTION
Iron is an essential trace metal in our diet and plays a key role in a plethora of
biochemical processes in the body including the binding and release of oxygen
in hemoglobin and electron transfer in mitochondrial oxidative phosphorylation
by the cytochromes. These processes can be compromised if dietary iron supply
is reduced with obvious consequences for human health. However, despite being
an essential nutrient, iron is a powerful pro-oxidant, and in excess can lead to
oxidative damage to cells and tissues through the formation of free radicals
(1). Consequently, body iron levels must be regulated within strictly defined
limits to avoid pathologies associated with iron deficiency and overload. The
major iron-related diseases are iron deficiency anemia, which affects up to 2
billion people and is regarded as the most prevalent nutritional deficiency dis-
order worldwide, and hereditary hemochromatosis, a genetic disease that predis-
poses 1 person in every 200 of northern European decent to body iron loading. To
maintain homeostatic control over iron nutriture, a number of regulatory mech-
anisms have evolved to match dietary iron absorption to the body’s physiological
requirements. This chapter will review the current knowledge regarding the
major iron-sensitive signals involved in the homeostatic regulation of body
iron metabolism.
