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Metal Ions in Life Sciences 13 Astrid Sigel Helmut Sigel Roland K.O. Sigel Editors Interrelations between Essential Metal Ions and Human Diseases Interrelations between Essential Metal Ions and Human Diseases Metal Ions in Life Sciences Volume 13 Series Editors: Astrid Sigel, Helmut Sigel, and Roland K.O. Sigel For further volumes: http://www.springer.com/series/8385 and http://www.mils-series.com Astrid Sigel • Helmut Sigel • Roland K.O. Sigel Editors Interrelations between Essential Metal Ions and Human Diseases Editors Astrid Sigel Helmut Sigel Department of Chemistry Department of Chemistry Inorganic Chemistry Inorganic Chemistry University of Basel University of Basel Spitalstrasse 51 Spitalstrasse 51 CH-4056 Basel CH-4056 Basel Switzerland Switzerland [email protected] [email protected] Roland K.O. Sigel Institute of Inorganic Chemistry University of Zürich Winterthurerstrasse 190 CH-8057 Zürich Switzerland [email protected] ISSN 1559-0836 ISSN 1868-0402 (electronic) ISBN 978-94-007-7499-5 ISBN 978-94-007-7500-8 (eBook) DOI 10.1007/978-94-007-7500-8 Springer Dordrecht Heidelberg New York London Library of Congress Control Number: 2014931237 © Springer Science+Business Media Dordrecht 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Historical Development and Perspectives of the Series Metal Ions in Life Sciences * It is an old wisdom that metals are indispensable for life. Indeed, several of them, like sodium, potassium, and calcium, are easily discovered in living matter. However, the role of metals and their impact on life remained largely hidden until inorganic chemistry and coordination chemistry experienced a pronounced revival in the 1950s. The experimental and theoretical tools created in this period and their appli- cation to biochemical problems led to the development of the fi eld or discipline now known as Bioinorganic Chemistry , Inorganic Biochemistry , or more recently also often addressed as Biological Inorganic Chemistry . By 1970 Bioinorganic Chemistry was established and further promoted by the book series Metal Ions in Biological Systems founded in 1973 (edited by H.S., who was soon joined by A.S.) and published by Marcel Dekker, Inc., New York, for more than 30 years. After this company ceased to be a family endeavor and its acquisition by another company, we decided, after having edited 44 volumes of the MIBS series (the last two together with R.K.O.S.) to launch a new and broader minded series to cover today’s needs in the Life Sciences . Therefore, the Sigels new series is entitled Metal Ions in Life Sciences. After publication of the fi rst four volumes (2006–2008) with John Wiley & Sons, Ltd., Chichester, UK, and the next fi ve volumes (2009–2011) with the Royal Society of Chemistry, Cambridge, UK, we are happy to join forces now in this still new endeavor with Springer Science & Business Media B.V., Dordrecht, The Netherlands; a most experienced Publisher in the Sciences . * Reproduced with some alterations by permission of John Wiley & Sons, Ltd., Chichester, UK (copyright 2006) from pages v and vi of Volume 1 of the series Metal Ions in Life Sciences (MILS-1). v vi Historical Development and Perspectives of the Series The development of Biological Inorganic Chemistry during the past 40 years was and still is driven by several factors; among these are (i) the attempts to reveal the interplay between metal ions and peptides, nucleotides, hormones or vitamins, etc., (ii) the efforts regarding the understanding of accumulation, transport, metabolism and toxicity of metal ions, (iii) the development and application of metal-based drugs, (iv) biomimetic syntheses with the aim to understand biological processes as well as to create effi cient catalysts, (v) the determination of high-resolution struc- tures of proteins, nucleic acids, and other biomolecules, (vi) the utilization of powerful spectroscopic tools allowing studies of structures and dynamics, and (vii), more recently, the widespread use of macromolecular engineering to create new biologically relevant structures at will. All this and more is and will be refl ected in the volumes of the series Metal Ions in Life Sciences . The importance of metal ions to the vital functions of living organisms, hence, to their health and well-being, is nowadays well accepted. However, in spite of all the progress made, we are still only at the brink of understanding these processes. Therefore, the series Metal Ions in Life Sciences will endeavor to link coordination chemistry and biochemistry in their widest sense. Despite the evident expectation that a great deal of future outstanding discoveries will be made in the interdisciplin- ary areas of science, there are still “language” barriers between the historically separate spheres of chemistry, biology, medicine, and physics. Thus, it is one of the aims of this series to catalyze mutual “understanding”. It is our hope that Metal Ions in Life Sciences proves a stimulus for new activities in the fascinating “fi eld” of Biological Inorganic Chemistry . If so, it will well serve its purpose and be a rewarding result for the efforts spent by the authors. Astrid Sigel and Helmut Sigel Department of Chemistry, Inorganic Chemistry, University of Basel, CH-4056 Basel, Switzerland Roland K.O. Sigel Institute of Inorganic Chemistry, University of Zürich, CH-8057 Zürich, Switzerland October 2005, October 2008, and August 2011 Preface to Volume 13 Interrelations Between Essential Metal Ions and Human Diseases Most of the 13 metals and 3 metalloids and their ions, which are covered in this volume, have been proven to be essential for humans. Indeed, it is an old wisdom that metal ions are indispensable for life. The main group metals, i.e., sodium, potassium, magnesium, and calcium, belong to the so-called bulk elements, and they occur in humans (70 kg) between about 20 g (Mg) and 1000 g (Ca) [H. Sigel, A. Sigel, H. G. Seiler, in Handbook on Metals in Clinical and Analytical Chemistr y, Eds H. G. Seiler, A. Sigel, H. Sigel, Dekker, New York, 1994, pp. 1–12]. The remaining 9 metals are transition elements, including zinc, and they all occur at trace levels, though iron and zinc dominate in humans with about 4 and 2.5 g, respectively. All the other metals, as well as the three metalloids (silicon, arsenic, selenium), occur only at ultra-trace levels, e.g., manganese and cobalt with about 12 and 1 mg, respectively. They comprise the essential elements manganese, cobalt, copper, molybdenum, and selenium; chromium, vanadium, nickel, silicon, and arse- nic have been proposed as being essential in the second half of the last century. However, it turned out that their essentiality is diffi cult to establish because, if at all, they are certainly needed only in ultra-trace amounts, and because of their preva- lence in the environment from natural and anthropomorphic sources, it has been diffi cult to prove whether or not there is a requirement for them, though the likeli- hood for vanadium and silicon as being essential appears to be high. The introductory Chapter 1 presents an overview of the topic, metal ions and infectious diseases, as seen from the clinic. The dilemma is that next to the bulk elements, also the trace elements are required by both, humans and bacterial patho- gens. Since these metal ions are both necessary for life, but toxic in excess, metal homeostasis is tightly controlled by both bacteria and humans. Thus, pathogens utilize a variety of strategies to sense, acquire, store, and export metal ions in/from the vertebrate host. vii viii Preface to Volume 13 The bulk elements sodium, potassium, magnesium, and calcium are dealt with in Chapters 2 to 4 . All these elements are essential for human health and the chapters summarize their basic physiological actions. For example, a proper cellular Mg 2+ homeostasis is in all instances compulsory; defi ciency or overload gives rise to dis- eases, and these are described. Interestingly, evolution has thoroughly exploited the chemical properties of Ca 2+ , i.e., its fast ligand-exchange rate and its reversible binding to sites with an irregular geometry, and selected it as a carrier of cellular signals.

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