Preface

Biochemistry is more than merely the chemistry of hydrogen, carbon, nitrogen, oxygen, sulfur and phosphorus. A significant number of additional elements of the periodic table are essential for life. In fact, life would not have evolved without them. Yet, after so many years of research, considerable uncertainty persists as to the complete list of elements that are essential to humans.

Non-essential elements are not innocent by-standers. Some interact with living systems and with essential elements, some have beneficial or pharmacological effects and yet others are toxic. Though we rarely monitor their concentrations, many of them are present in living systems, some of them at higher concentrations than essential elements, and our knowledge of how they affect biological function remains limited. Due to new industrial applications and manufacturing processes, we continue to introduce new chemical species and rare elements into the environment. This poses a considerable risk to unprotected biological systems, the stability of ecosystems and, of course, our health. Nanomaterials are one but not the only example. Thus, the study of the non-essential elements, traditionally an area of toxicology, gains importance similar to that of the essential elements, traditionally an area of nutrition.

Homeostatic control maintains the essential elements at their required concentrations. This control involves a large number of processes. It avoids negative effects associated with either deficiency or overload. We need to understand the chemistry underlying metal ion overloads and deficiencies in order to define pathophysiological mechanisms. This area is receiving increased attention because perturbation of homeostatic control of some elements is associated with causation, symptoms or progression of genetic, infectious and degenerative diseases, including neurodegeneration, cancer and diabetes. Detoxification of some non-essential elements also involves biological control and specific chemical and biological mechanisms. Such processes can be mistaken for homeostatic control. For yet other non-essential elements with chemical characteristics similar to essential elements, detoxification mechanisms may not be in place and these elements can have pleiotropic actions.

This book focuses on the binding, storage and transport of metal ions in biological systems. All these functions require specific chemistries, coordination dynamics and selectivity in transient binding of metal ions.

Metals are involved in the biochemistry of gases including those involving nitrogen (N₂, NH₃, NO), carbon (CH₄, CO, CO₂), hydrogen (H₂), oxygen (O₂) and sulfur (SO, SO₂). This includes the fixation of these elements in biological matter and geo-biochemical cycles. Metal ions support fundamental biological functions in catalysis, structure and regulation, including the establishment of electrochemical potentials across membranes for energy generation and communication. This inorganic aspect of biochemistry is as important as its organic aspects. About 50% of all proteins contain a metal cofactor. The protein machinery that controls metal ions in cells is extensive, and how those ions are bound, stored and transported is critical to all their diverse functions. Cells are loaded with metal ions and even some considered as trace elements occur at remarkably high concentrations. But there are also pools of non-protein bound metal ions that are reactive and can be catalytically or biologically active.

This book does not address all the functions of metal ions in biology but rather how they are handled and controlled. We took the periodic table as a basis for the book and the line between metals and non-metals, which led to the exclusion of certain metalloids. Some metals are not discussed (Li, Be, Sn, lanthanides) due to a lack of molecular information. We plan to include them in future editions. We also largely excluded specific processes that biology employs to scavenge metal ions outside the cell, e.g. siderophores for iron and similar compounds for other metal ions, plus cellular processes that involve complex cofactors for metal ions, e.g. haem. Each chapter addresses the biochemistry of one particular element, with the exception of the chapter on metallothioneins, which discusses their involvement in the metabolism of several metals. Regarding biology, we focus in a textbook-like way on general aspects of the inorganic biochemistry of either prokarya or eukarya. Some authors have chosen to discuss plants. The usage of essential elements differs in organisms and while some are essential in some organisms they are not in others. Such aspects of biological variety are rarely considered and neither are protection mechanisms that also vary between organisms.

The knowledge presented here is necessary for defining nutritional requirements, thresholds for toxicity and disease-causing mechanisms. It is also the key to the mechanisms of action of metallodrugs and to the interactions of metal ions with biomolecules when used in the imaging of cells and tissues. The contributing authors are working in different scientific disciplines. We believe that, in addition to the inherently inter- and multidisciplinary nature of the subject matter, the different views of the authors provide the reader with broader perspectives. We also hope that the book will raise the interest of scientists from many disciplines. We noticed that investigations have become so narrowly focused that “independent” fields develop unique terminologies for each metal ion. This book attempts to surmount this issue by taking a metallomics approach. We asked the authors to discuss the same broad questions but they came up with different and sometimes conflicting answers. We attempted an approach that transcends investigations of the interaction between metals and biomolecules in vitro as we were asking the authors to address how metal ions are controlled in the cell and whether or not the phenomena observed are physiologically relevant and meaningful.

We acknowledge advice from David Giedroc, Robert Haussinger, Barry Rosen and Dennis Winge.