Iron Metabolism

194 Pages·2012·5.4 MB·English

by  S. Arora

IRON METABOLISM

Edited by Sarika Arora
Iron Metabolism
Edited by Sarika Arora

Published by InTech
Janeza Trdine 9, 51000 Rijeka, Croatia

Copyright © 2012 InTech
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First published June, 2012
Printed in Croatia

A free online edition of this book is available at www.intechopen.com
Additional hard copies can be obtained from [email protected]

Iron Metabolism, Edited by Sarika Arora
p. cm.
ISBN 978-953-51-0605-0

Contents

Preface VII
Section 1 Systemic Iron Metabolism in Physiological States 1
Chapter 1 Iron Metabolism in Humans: An Overview 3
Sarika Arora and Raj Kumar Kapoor
Section 2 Cellular Iron Metabolism 23
Chapter 2 Cellular Iron Metabolism –
The IRP/IRE Regulatory Network 25
Ricky S. Joshi, Erica Morán and Mayka Sánchez
Section 3 Functional Role of Iron 59
Chapter 3 Relationship Between Iron and Erythropoiesis 61
Nadia Maria Sposi
Section 4 Iron Metabolism in Pathological States 87
Chapter 4 Iron Deficiency in Hemodialysis Patients –
Evaluation of a Combined Treatment
with Iron Sucrose and Erythropoietin-Alpha:
Predictors of Response, Efficacy and Safety 89
Martín Gutiérrez Martín, Maria Soledad Romero Colás,
and José Antonio Moreno Chulilla
Chapter 5 Role of Hepcidin in Dysregulation
of Iron Metabolism and Anemia of Chronic Diseases 129
Bhawna Singh, Sarika Arora, SK Gupta and Alpana Saxena
Section 5 Iron Metabolism in Pathogens 145
Chapter 6 Iron Metabolism in Pathogenic Trypanosomes 147
Bruno Manta, Luciana Fleitas and Marcelo Comini

Preface

Iron is the most abundant element on earth representing nearly 90% of the mass in the
earth’s core, yet only trace elements are present in living cells. Most of the iron in the
body is located within the porphyrin ring of heme, which is incorporated into proteins
such as hemoglobin, myoglobin, cytochromes, catalases and peroxidases. Although
iron appears in a variety of oxidation states, in particular as hexavalent ferrate, the
ferrous and ferric forms are of most importance. The transition from ferrous to ferric
iron and vice versa occurs readily, meaning that Fe(II) acts as a reducing agent and
Fe(III) as an oxidant. Iron is closely involved with the metabolism of oxygen in a
variety of biochemical processes. Iron, as either heme or in its “nonheme” form, plays
an important role in cell growth and metabolism because of its involvement in key
reactions of DNA synthesis and energy production.
However, low solubility of iron in body fluids and the ability to form toxic hydroxyl
radicals in presence of oxygen make iron uptake, use and storage a serious challenge.
Iron metabolism in complex organisms involves two levels of regulation. The lower
level is cellular and comprises the mechanisms of cellular uptake and storage as well
as the intracellular use of iron in enzymes. In this regard, two principles effectively
control iron uptake, the use of cell surface receptors for iron-containing proteins or
direct iron import by metal transporters. This aspect has been studied in detail during
the last three decades with a special focus on the mechanisms and regulation of
receptor-mediated cellular iron uptake and storage. In contrast, the knowledge about
the upper level of iron metabolism, the systemic level, was inadequate up to the end of
the last century. This involves various unsolved questions pertaining to the regulation
of intestinal iron uptake, various signalling pathways involved in the iron demand of
individual cells and how these signals are transmitted to the iron stores and the
intestine. The discovery of new metal transporters, receptors and peptides and as well
as the discovery of new cross-interactions between known proteins are now leading to
a breakthrough in the understanding of systemic iron metabolism. The objective of this
book is to review and summarize recent developments in our understanding of iron
transport and storage in living systems and how iron metabolism may be affected in
anemias associated with chronic diseases and hemodialysis patients. It begins with a
focus on normal systemic iron metabolism in humans focusing on the role of various
iron containing proteins and the mechanisms involved in iron absorption and
utilization. It then progresses to a detailed review on Cellular Iron metabolism with a
VIII Preface

special focus on the IRP/IRE regulatory network. One of the major roles of iron is in
erythropoiesis which has been appropriately covered in one of the chapters. Though
the emphasis is on human iron metabolism in physiological and pathological states,
further knowledge is derived from the chapter on iron metabolism in pathogenic
trypanosomes. These parasites have developed distinct strategies to scavenge
efficiently iron from the surrounding medium and support their metabolic needs,
which differ between trypanosomatid species and life stages.
This book provides knowledge about iron metabolism and related diseases in 6
coordinated Chapters which can also be read as stand-alone. The new and essential
path breaking insights into iron metabolism have been addressed in this book.
Together with the efforts of experienced and committed authors who spent their time
and fundamentally contributed to the success of this book, I hope that a number of
readers will enjoy the review Chapters and find a lot of information to develop new
ideas in this rapidly ongoing field of investigation.

Dr Sarika Arora
Department of Biochemistry
ESI Postgraduate Institute of Medical Sciences & Research
Basaidarapur, New Delhi
India
Section 1
Systemic Iron Metabolism
in Physiological States