Print and Media Review

Abstract

The field of iron metabolism is probably one the fastest moving areas in science. In the past few years, new genes, proteins, and diseases have been recognized, and genetic studies now foresee the discovery of other important iron-related genes. No doubt that such an intense scientific activity and the growing number of novel information justifies a review of the latest developments in the field. However, the rapidly changing scene of iron metabolism makes it difficult to structure a comprehensive description and interpretation of available scientific data. The actual function of most of the new proteins in vivo, their coordinated regulation in the context of body iron trafficking, and the way lack-of-function mutations may lead to hereditary diseases in humans, are still uncertain and a matter of intense debate. Dr. Testa has undertaken a courageous editorial challenge and has compiled a series of highly authoritative chapters on genetics, biochemistry, physiology, and cell biology of iron proteins. Traditionally, until the 1970s, our understanding of the control of iron homeostasis in mammals and its deregulation in iron-loading disorders was based on the role of a few proteins, such as ferritins, serum transferrin, and the cellular receptor for transferrin, the transferrin receptor 1. Additional insights provided by a further 20 years of investigation led to the discovery of the iron-regulatory proteins, IRP-1 and IRP-2, at the same time sensors for cytoplasmic iron and controllers of ferritin and transferrin receptor expression. The IRP system still holds as best characterized example of posttranscriptional regulation of gene expression. In recent years, an unexpectedly fast progress in iron research has further changed the scene. New genes have been discovered including the hemochromatosis (HFE) gene, the metal transporters divalent-metal transporter 1 and ferro-portin1/IREG1/MTP1 and their molecular reductase/oxidase partners (e.g., duodenal cytochrome b and hephestin), a second transferrin receptor (transferrin receptor 2), the iron-hormone hepcidin. This has greatly complicated the simple picture of iron homeostasis depicted in the early literature. Most of these developments in iron metabolism have been covered in this review and the reader can certainly feel this new excitement throughout the book, particularly when reading the chapters on general aspects of iron metabolism and absorption. The book is particularly strong when holding a mirror up to biochemistry and biology of "classical" iron proteins, such as transferrins, lactoferrin, transferrin receptors, iron-regulatory proteins, and ferritins. Specific sections are devoted to these proteins where specialists may find up-to-date information, clear figures and illustrations, and valuable bibliographic resources. The author has put special care into describing results of most available reports on specific aspects of iron protein biology and expression. Obviously, due to the rapid progress of the field, the latest findings on new iron-proteins, could not be included in this book. Two chapters on specific physiological aspects of iron metabolism such as iron absorption and iron in cell proliferation have been also included. A nonspecialized reader may find difficult to integrate the extensive basic description provided for each iron protein within the general context of iron trafficking or the pathogen-esis of human iron disorders. Although the declared focus of the book is genetics, biochemistry, and biology of iron proteins , some expectation had been generated by the author when it comes to description of physiological aspects of iron metabolism or pathogenic effects of deregulated iron homeostasis. There is some difficulty in drawing a comprehensive picture and in integrating the traditional concepts of iron metabolism with the new acquisitions. Sometimes it is difficult to follow the logic because concepts are repeated in different chapters but with slightly different emphasis or interpretation, as in the case of pathophysiology of hemochromatosis and the function of the HFE protein. There has been an attempt toward a more comprehensive and choral description of iron metabolism and its derangements, but this has been confined to the introductory chapter. Here, the author appears more prone to include all available published information than to use his competence and knowledge to interpret and integrate it. Despite these minor disappointments, the book is a well-written and tight collection of compelling and informative chapters on biochemistry and cell biology of iron proteins, each one clearly contributing to the development of the overall argument. Bottom Line: A state-of-the-art review of research in iron metabolism.