Biological Inorganic Chemistry

An Introduction

Robert R. Crichton

• Publisher: Elsevier Science
• Year: 2007
• ISBN:
  9780080556222
• Topic: Scienze fisiche
• Subtopic: Chimica inorganica

The importance of metals in biology, the environment and medicine has become increasingly evident over the last twenty five years. The study of the multiple roles of metal ions in biological systems, the rapidly expanding interface between inorganic chemistry and biology constitutes the subject called Biological Inorganic Chemistry. The present text, written by a biochemist, with a long career experience in the field (particularly iron and copper) presents an introduction to this exciting and dynamic field. The book begins with introductory chapters, which together constitute an overview of the concepts, both chemical and biological, which are required to equip the reader for the detailed analysis which follows. Pathways of metal assimilation, storage and transport, as well as metal homeostasis are dealt with next. Thereafter, individual chapters discuss the roles of sodium and potassium, magnesium, calcium, zinc, iron, copper, nickel and cobalt, manganese, and finally molybdenum, vanadium, tungsten and chromium. The final three chapters provide a tantalising view of the roles of metals in brain function, biomineralization and a brief illustration of their importance in both medicine and the environment.Relaxed and agreeable writing style. The reader will not only fiind the book easy to read, the fascinating anecdotes and footnotes will give him pegs to hang important ideas on.Written by a biochemist. Will enable the reader to more readily grasp the biological and clinical relevance of the subject.Many colour illustrations. Enables easier visualization of molecular mechanismsWritten by a single author. Ensures homgeneity of style and effective cross referencing between chapters

1

An Overview of Metals in Biology

Publisher Summary

The human body is made up of 99.9% of just 11 elements, 4 of which hydrogen, oxygen, carbon and nitrogen account for 99% of the total. This chapter provides the indications of the multiple roles, for good as well as for ill, of a number of other metal ions, other than these four, that play an important role in living organisms. The study of the roles of metal ions in biological systems represents the exciting and rapidly growing interface between inorganic chemistry and the living world. The water-splitting centre of green plants, which produces oxygen, is based on the sophisticated biological use of manganese chemistry. Metals such as cadmium, manganese and lead in our environment represent a serious health hazard. Cadmium is present in substantial amounts in tobacco leaves, so that cigarette smokers on a packet a day can easily double their cadmium intake. Yet, while many metals are toxic, many key drugs are metal based—examples are cisplatin and related anticancer drugs, and lithium carbonate, used in the treatment of manic depression. Paramagnetic metal complexes are widely used as contrast agents for magnetic resonance imaging (MRI). Numerous trace metals are also required to ensure human health; and while metal deficiencies are well known, it is evident that excessive levels of metals in the body can also be toxic. It describes the advantages and disadvantages of different essential metal ions like, hydrogen, lithium, helium, aluminium, magnesium, sodium, fluorides, potassium, calcium, chlorides, silicon, etc.

INTRODUCTION

The importance of metals in biology, the environment and medicine has become increasingly evident over the last 25 years. The movement of electrons in the electron-transfer pathways of photosynthetic organisms and in the respiratory chain of mitochondria, coupled to proton pumping to enable the synthesis of ATP, is carried out by iron- and copper-containing proteins (cytochromes, iron–sulfur proteins and plastocyanins). The water-splitting centre of green plants (photosystem II), which produces oxygen, is based on the sophisticated biological use of manganese chemistry. Metals such as cadmium, manganese and lead in our environment represent a serious health hazard. Cadmium is present in substantial amounts in tobacco leaves, so that cigarette smokers on a packet a day can easily double their cadmium intake. Yet, while many metals are toxic, many key drugs are metal based—examples are cis-platin and related anticancer drugs, and lithium carbonate, used in the treatment of manic depression. Paramagnetic metal complexes are widely used as contrast agents for magnetic resonance imaging (MRI). Numerous trace metals are also required to ensure human health; and while metal deficiencies are well known (for example inadequate dietary iron causes anaemia), it is evident that excessive levels of metals in the body can also be toxic.

It has been clear from the outset that the study of metals in biological systems can only be approached by a multidisciplinary approach, involving many branches of the physical and biological sciences. The study of the roles of metal ions in biological systems represents the exciting and rapidly growing interface between inorganic chemistry and the living world. It has been defined by chemists as bioinorganic chemistry, and by biochemists as inorganic biochemistry. From 1990 to 1997 the European Science Foundation funded a programme on the Chemistry of Metals in Biological Systems¹. This resulted, in the course of what turned out to be monumentally important meeting held in the Tuscan town of San Miniato, in the launching of important initiatives around the international consensus name ‘Biological Inorganic Chemistry’. The outcome was the creation of the Society of Biological Inorganic Chemistry (SBIC) and the Journal of Biological Inorganic Chemistry (JBIC). These then joined the already existing International Congress of Biological Inorganic Chemistry (ICBIC) and European Congress of Biological Inorganic Chemistry (EUROBIC) to form a series of acronyms; all now use the stylized French word for a ballpoint pen ‘bic’ to designate the term biological inorganic chemistry. I use this definition in this book, but would like to indicate to the prospective reader that this text will deal to a much greater extent with the biochemical aspects of metals in living systems rather than with their inorganic chemistry.

WHY DO WE NEED ANYTHING OTHER THAN C, H, N AND O (TOGETHER WITH SOME P AND S)?

Organic is defined as ‘designating the branch of chemistry dealing with carbon compounds’, or ‘designating any chemical compound containing carbon’, although the interesting codicil is added, in the latter definition, that some of the simple compounds of carbon, such as carbon dioxide, are frequently classified as inorganic compounds. Of course, in the world of organic foodstuffs (grown with only animal or vegetable fertilizers) the word takes a broader connotation, signifying production from the detritus of living organisms. And, when we come to examine the biotope, we quickly perceive that carbon alone does not suffice for life. We also need oxygen, hydrogen, nitrogen, a non-negligible dose of phosphorus, as well as some sulfur.

But these elements alone do not enable life as we know it to exist, in its multiple and varied forms we need components of inorganic chemistry as well. If we were to ask for a definition of inorganic chemistry (previously defined in French as mineral chemistry), we would find ourselves confronted with a world that was not organic, nor of animal or vegetable origin—most inorganic compounds do not contain carbon, and are derived from mineral sources. Yet this inanimate chemistry, apparently with nothing to do with living systems, has a crucial role to play in our understanding of the biological world. So we can recognize that in the course of evolution, Nature has selected constituents not only from the organic world but also from the inorganic world to construct living organisms. Some of these inorganic elements, such as sodium and potassium, calcium and magnesium, are present in quite large concentrations, and tend to be known as ‘bulk elements’, on a scale with those cited in the first paragraph. Others, such as cobalt, copper, iron and zinc, are known as ‘trace elements’, with dietary requirements that are much lower than the bulk elements.

Indeed, the human body is made up of 99.9% of just 11 elements, 4 of which (hydrogen, oxygen, carbon and nitrogen) account for 99% of the total (62.8%, 25.4%, 9.4% and 1.4%, respectively). Why we require as many as 25 elements in total from the periodic table will become clearer as we advance in this chapter, but one thing shines out, namely that these elements have been selected on the basis of their suitability for the functions that they are called upon to play, in what is predominantly an aqueous environment².

Na⁺ and K⁺ (together with H⁺ and C1⁻), which bind weakly to organic ligands (Table 1.1), are ideally suited in generating ionic gradients across membranes and for the maintenance of osmotic balance. In contrast, Mg²⁺ and Ca²⁺ with intermediate-binding strengths to organic ligands, can play important structural roles, and in the particular case of Ca²⁺, serve as a charge carrier and a trigger for signal transmission. Zn²⁺ not only plays a structural role but can also fulfil a very important function as a Lewis acid. Redox metal ions, such as iron and copper, which bind tightly to organic ligands, participate in innumerable redox reactions, besides playing an important role in oxygen transport. We now discuss the essential metal ions and thereafter briefly review their roles.

Table 1.1

Correlations between ligand binding, mobility and function of some biologically relevant metal ions

Metal ion	Binding	Mobility	Function
Na^+, K^+	Weak	High	Charge carriers
Mg^2+, Ca^2+	Moderate	Semi-mobile	Triggers, transfers structural
Zn^2+	Moderate/strong	Intermediate	Lewis acid, structura...

Table of contents

• Cover image
• Title page
• Table of Contents
• Preface
• Chapter 1: An Overview of Metals in Biology
• Chapter 2: Basic Coordination Chemistry for Biologists
• Chapter 3: Biological Ligands for Metal Ions
• Chapter 4: Structural and Molecular Biology for Chemists
• Chapter 5: An Overview of Intermediary Metabolism and Bioenergetics
• Chapter 6: Methods to Study Metals in Biological Systems
• Chapter 7: Metal Assimilation Pathways
• Chapter 8: Transport, Storage and Homeostasis of Metal Ions
• Chapter 9: Sodium and Potassium—Channels and Pumps
• Chapter 10: Magnesium–Phosphate Metabolism and Photoreceptors
• Chapter 11: Calcium: Cellular Signalling
• Chapter 12: Zinc: Lewis Acid and Gene Regulator
• Chapter 13: Iron: Essential for Almost All Life
• Chapter 14: Copper: Coping with Dioxygen
• Chapter 15: Nickel and Cobalt: Evolutionary Relics
• Chapter 16: Manganese: Water Splitting, Oxygen Atom Donor
• Chapter 17: Molybdenum, Tungsten, Vanadium and Chromium
• Chapter 18: Metals in Brain and Their Role in Various Neurodegenerative Diseases
• Chapter 19: Biomineralization
• Chapter 20: Metals in Medicine and the Environment
• Index