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Biochemistry in the modern world S t ud y Go a l s After reading this chapter you will: •• understand what we mean by the term ‘biochemistry’ •• be aware of the central position that biochemistry occupies within the biological sciences •• appreciate that to understand biochemistry it is also necessary to understand the basic principles of chemistry •• know that four types of large molecule – proteins, nucleic acids, lipids and polysaccharides – are particularly important in biochemistry •• be aware that metabolism plays a vital role in all living organisms
•• recognize that metabolism includes catabolic processes, which break molecules down to generate energy, and anabolic ones, which build up larger molecules from small ones •• know that biological information is stored in DNA and made available to the cell via the process called gene expression •• realize that biochemistry is an experimental science and that understanding the methods used in research projects is a key part of becoming a biochemist
Imagine you mixed together a few kilograms of oxygen, carbon, hydrogen, nitrogen, calcium and phosphorus, with smaller amounts of some 53 other elements from aluminum to zirconium, using the recipe in Table 1.1. What would you have? A rather bizarre mix of solid, liquid and gaseous chemical elements, which is odd, because the average adult human is made up of the same elements in the same proportions. But outside of the world of cult movies, no amount of heating, electrifying or irradiating will turn the mixture into a living person. Biochemistry tells us why.
What is biochemistry? When I studied biochemistry at university it was quite common for a hyphen to be inserted in the word, so it was written as bio-chemistry. The longer term ‘biological chemistry’ is still used today. The implication is that biochemistry is simply a combination of the two subjects, chemistry applied to biology, or the ‘chemistry of life’. This is a reasonable way to define biochemistry in half a dozen words, but modern biochemistry is, in reality, much more than just the study of the chemicals present in living organisms. Let us explore exactly what we mean by ‘biochemistry’.
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2 | Ch a p ter 1 | Biochemistry in the modern world Table 1.1. The elemental composition of the average adult human
Amount in a 70 kg human
43 kg (61%)
16 kg (23%)
7 kg (10%)
1.8 kg (2.5%)
1.0 kg (1.4%)
780 g (1.1%)
140 g (0.20%)
140 g (0.20%)
100 g (0.14%)
95 g (0.14%)
19 g (0.03%)
Trace amounts (less than 100 mg each) of copper, aluminum, cadmium, cerium, iodine, tin, titanium, boron, nickel, selenium, chromium, manganese, arsenic, lithium, cesium, mercury, germanium, molybdenum, cobalt, antimony, silver, niobium, zirconium, lanthanum, gallium, tellurium, yttrium, bismuth, thallium, indium, gold, scandium, tantalum, vanadium, thorium, uranium, samarium, beryllium and tungsten Those elements shown in red are known to play a role in human biochemistry. Most of the other elements are absorbed from the environment but have no known function within the body. Data from Emsley J (1998) The Elements, 3rd edn. Clarendon Press, Oxford.
1.1.1 Biochemistry is a central part of biology Biochemistry is a part of biology, or of the life sciences as the subject is now commonly called. Within the life sciences, biochemistry occupies a central position. This is because biochemistry is concerned with the synthesis and structure of the molecules that make up living organisms, and with the way in which chemical reactions provide organisms with the energy they need to survive. Biochemistry therefore explains how the mixture of atoms described in Table 1.1 can be combined together to make a living, functioning human being. In doing so, biochemistry underpins our understanding of all aspects of biology, and biologists who do not look on themselves as biochemists still have to understand the subject, and often have to use biochemistry in their own studies. For some areas of the life sciences, it is very easy to see why a knowledge of biochemistry is important. Biologists who study the structures and properties of living cells, for example, cannot proceed very far in their research without considering the molecules contained in those cells. These molecules make up the structure of the cell and are responsible for each cell’s particular properties (Fig. 1.1). So there is a great deal of overlap between biochemistry and cell biology. The same is true for genetics, which focuses on the genetic information contained in genes. Genes are made of DNA, and understanding how genes work means studying the structure of DNA and the way in which DNA interacts with other molecules so that the information it contains can be used by the cell. These are exactly the same questions that biochemists are interested in, and a large part of genetics could be described as ‘the biochemistry of DNA’.
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1.1 | What is b io c hemis tr y? | 3 Figure 1.1 Representation of part of a cell of the bacterium Escherichia coli. The cell wall, which is made up mainly of carbohydrate and protein, is shown in green, as is the cell membrane and a flagellum, the latter extending from the cell wall. The flagellum is made of protein, and rotates like a propeller, enabling the bacterium to swim at speeds up to 100 µm per second. Within the cell, the long yellow strands are parts of the bacterium’s DNA molecule, which in places is wrapped around barrel-shaped proteins, also shown in yellow. The orange structures are enzymes that are making RNA copies of the genes in the DNA molecule. These copies, called messenger RNA, are shown in white. They move to the purple ribosomes (made of RNA and protein) where they direct the synthesis of new proteins. These proteins include enzymes, in blue, that catalyze the biochemical reactions occurring within the bacterium. Illustration by David S. Goodsell, the Scripps Research Institute, and reproduced here with permission.
Modern biochemistry also underpins areas of biology that we associate with organisms rather than cells. In ecology, for example, ecosystems are often described in terms of food webs, with energy being generated by photosynthesis and then transferred up a food chain through the herbivores to the top carnivores (Fig. 1.2). The generation of energy is a central topic in biochemistry, and this aspect of ecosystem ecology is, in reality, biochemistry applied to a community of different species rather than to individual organisms. Similarly, we do not immediately think of biochemistry when evolution is being discussed. But the evolutionary relationships between species are now studied not only by comparing the morphology of those species and the structures of their bones. Today, the relationships are more likely to be probed by comparing the structures of the molecules contained in the organisms (Fig. 1.3). Evolutionary biologists must therefore learn biochemical techniques in order to work out those molecular structures, and must understand biochemistry to make sure that the comparisons that they make are based on sound principles. Because biochemistry is so central to the life sciences, we must begin this book with a brief survey of the key principles of biology, to provide the context for our study of molecules and their biochemical reactions. We do this in Chapter 2, where we will look at the variety of life on the planet, examine the structures of cells, and consider how the vast diversity of life arose.
1.1.2 Chemistry is also important in biochemistry Although biochemistry is part of the life sciences, it depends very much on the principles and analytical methods of chemistry. Indeed, biochemistry began when chemists first
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4 | Ch a p ter 1 | Biochemistry in the modern world Figure 1.2 Movement of energy through the food web of the African savannah. Energy from the sun is captured by photosynthesis that takes place in the primary producers. Herbivores obtain their energy by eating primary producers, and herbivores are in turn eaten by carnivores. The energy from sunlight is therefore transferred, step by step, up the food chain.
Figure 1.3 Evolutionary relationships among the mammals. Trees like this used to be constructed from morphological information, but today are more likely to be deduced by comparing the structures of proteins or DNA molecules from the species being studied.
Box 1.1 The origins of biochemistry The German chemist Carl Neuberg is looked on as the father of biochemistry. Neuberg introduced the term ‘biochemistry’ in 1903, and promoted biochemistry as a distinct subject by setting up and editing the Biochemische Zeitschrift, the first journal devoted to biochemistry, now called FEBS Journal. However, the origins of biochemistry date back much further, to the mid-1700s when scientists first began to study chemicals and chemical processes in living organisms. This work gradually overturned the long-standing notion that living entities contain a ‘vital principle’ which cannot be described in chemical or physical terms. By 1900 it had been established that living organisms are subject to the same chemical and physical laws as inanimate matter, enabling all areas of biology, not just biochemistry, to develop into the rigorous scientific disciplines with which we are familiar today. The key steps in the development of biochemistry prior to 1900 were as follows: 1770s Carl Wilhelm Scheele isolated citric acid from lemons, malic acid from apples, and lactic acid from milk. These carbohydrates were among the first organic compounds to be identified. 1780s Antoine Lavoisier and Pierre Laplace showed that the amount of heat and carbon dioxide generated during respiration is identical to that generated during combustion. Lavoisier also proposed that, during photosynthesis, plants take up carbon dioxide and release oxygen. These experiments indicated that energy generation in living organisms is subject to the same chemical laws as energy generation in chemical reactions.
1811–1823 Michel Eugène Chevreul studied the chemistry of animal fats. His work was the first application of chemical and physical analysis to any type of biomolecule. 1820s William Prout distinguished different types of food as saccharinous, albuminous and oleaginous, which are roughly equivalent to carbohydrates, proteins and fats. 1827 Hans Fischer synthesized porphyrins and showed that these compounds bind oxygen in red blood cells. 1833 Anselm Payen and Jean-François Persoz isolated and studied the first enzyme, ‘diastase’, which we now call amylase and which converts starch to sugar. We will examine their work in more detail in Section 7.1. 1850s Claude Bernard showed that glycogen is synthesized from glucose in the liver. This was one of the first demonstrations that animals are able to synthesize biomolecules as well as break them down. 1877 Moritz Traube suggested that enzymes are a type of protein. 1880–1900 Emil Fischer identified the structures of many important biomolecules, including the 16 different isomers of glucose, and the purines that are components of DNA and RNA. Later, he showed how amino acids are linked together to form a polypeptide. 1895–1900 The first hormones were discovered. Adrenaline (also called epinephrine) was identified by Napoleon Cybulski, Jokichi Takamine and others.
became interested in studying the chemical reactions that occur in living organisms. These chemists discovered, back in the nineteenth century, that biochemistry presents its own unique challenges. Foremost among these is the complexity of the mixture of molecules that are present in a living cell. Chemists were, and still are, more used to studying reactions that occur in relatively simple solutions whose chemical makeup is precisely known. Cells, and extracts prepared from cells, contain many different types of compound, and understanding which parts of the mix are responsible for particular biochemical reactions is a real problem. Solving this problem required the development of new methods and scientific approaches that gave biochemistry a unique flavor. Chemistry, on the other hand, continued to be organized around the traditional split of inorganic, organic and physical. Biochemistry fits into neither of these categories, and so became a subject in its own right. Although biochemistry grew up as a separate subject, it is not possible to study biochemistry or to be a biochemist without understanding the basic principles of chemistry. For some young biochemists, especially those who are drawn to the subject because of an interest in biology, learning chemistry is a daunting prospect. The very first lecture that I attended at university was in a Physical Chemistry unit and was on the Schrödinger wave equation. The class began with the lecturer writing the equation (or one of them, there are several versions) on the blackboard. To say I was daunted would be an understatement; at the time I did not even understand what half the symbols meant. It would also be true to say that since completing that unit in Year 1 Physical Chemistry, I have never needed to refer to Schrödinger’s equation ever again.
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See p. xx for a list of all the Principles of Chemistry boxes.
In this book we will not follow my undergraduate experience and plunge straight into the deep end of chemistry. Instead we will deal only with those aspects of chemistry that are important in biochemistry, and we will deal with those topics as and when they become relevant. Most of these chemical topics will be presented in bite-sized units as a series of orange ‘Principles of Chemistry’ boxes that you will meet at the appropriate places as we progress through the book.
Box 1.2 Schrödinger and biology Although Erwin Schrödinger is most noted for his work on quantum theory, he was one of several physicists from the early part of the twentieth century who also took a keen interest in biology. One of these, Max Delbrück, changed disciplines mid-career, moving from theoretical physics to genetics and carrying out pioneering work with bacteriophages (viruses that infect bacteria) that led to the discovery that genes are made of DNA. Schrödinger remained a physicist, but in 1944 he wrote a short book called What is Life?, in which he speculated about inheritance and the structure of genes. Reading the book today, many of Schrödinger’s ideas appear far-fetched. He concludes that genes are crystalline structures, and in places he comes close to reviving the ‘vital principle’ of pre-twentieth century
biology, by suggesting that living organisms might utilize unknown laws of physics. Despite its errors, in one respect What is Life? was an important landmark in the development of twentieth century biochemistry. It had already been established that genes contain information that specifies the developmental plan of an organism and the biochemical reactions that it can carry out. Schrödinger argued that this information must be encoded within the structures of the organism’s genes. Again, his specific ideas about how this coding system worked were incorrect, but the notion that there must be some kind of genetic code that an organism uses to read the information in its genes was an important insight that set the agenda for research into genes over the next 20 years. In Section 16.1 we will explore how information is encoded in a gene and how this information is utilized.
Biochemistry involves the study of very large biomolecules
When the first biochemists began to examine the complex mixtures of molecules in living cells, they quickly realized that some of these molecules are very large indeed. The size of a molecule is expressed as its molecular mass, measured in Daltons (Da), with 1 Da equal to one-twelfth the mass of a carbon atom. Most of the compounds known in nature, and most of the artificial ones synthesized by chemists, have molecular masses substantially less than 1000. Water, for example, has a molecular mass of 18.02 Da, ethanol is 46.07 Da, and phenol is 94.11 Da. Even a complex organic compound such as quinine, which is used to treat malaria, has a molecular mass of only 324 Da. In contrast, there are many molecules in living cells whose molecular masses are measured in thousands of Daltons, called kiloDaltons (kDa). Relatively small examples of these macromolecules include thrombin, which is involved in blood clotting and whose molecular mass is approximately 37 400 Da or 37.4 kDa, and alpha-amylase, which is secreted in saliva and begins the breakdown of dietary starch into sugar, which has a mass of 55.4 kDa. Starch itself is variable in size, ranging from 190 kDa to 227 000 kDa depending on which type of plant it comes from.
Figure 1.4 A linear polymer. BIOCHEMISTRY | Chapter 01 | Figure 04
Most of these large biomolecules are polymers, compounds made up of long chains of identical or very similar chemical units called monomers (Fig. 1.4). In starch, the monomeric unit is a glucose molecule, and the polymer is built up by linking glucose monomers together in branched chains. The greater the number of glucose units, the larger the molecular mass of the starch molecule. One of the smaller starch molecules, with a molecular mass of just 190 kDa, would contain about 1050 glucose units, whereas the larger molecules will have over a million. Starch is an example of a polysaccharide, a polymer made of glucose or similar sugar molecules. Polysaccharides have two main roles in living cells. First, polysaccharides such as starch (in plants) and glycogen (in animals) act as stores of energy. This is
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Box 1.3 Atoms, isotopes and molecular masses An atom consists of a nucleus containing positively charged protons and neutral neutrons, surrounded by a cloud of negatively charged electrons. The chemical identity of the element is determined by the number of protons, which is called the atomic number. This number is the same for all atoms of that particular element. For example, every hydrogen atom has just a single proton and an atomic number of 1, and every carbon atom has six protons and an atomic number of 6. electron (–) proton (+) neutron nucleus
PR I N C I PLE S O F C HE M I S TRY different versions of an element are called isotopes. Carbon, for example, has three naturally occurring isotopes, each containing six protons but with six, seven or eight neutrons. The total number of protons and neutrons in a nucleus is called the mass number, so the three isotopes of carbon have mass numbers of 12, 13 and 14, and are called carbon-12, carbon-13 and carbon14, or 12C, 13C and 14C. These are the isotopes of carbon that are found in nature. Carbon-12 makes up 98.93% of all the carbon atoms in existence, and carbon-13 contributes most of the remaining 1.07%. Carbon-14 is present in only trace amounts, about one out of every trillion carbon atoms. There are also 12 isotopes from 8C to 22C that do not exist in measurable amounts in the environment but which can be created under laboratory conditions. The majority of elements, but not all, have naturally occurring isotopes, the largest numbers being nine isotopes for xenon and ten for tin. Carbon-12 is considered to have a molecular mass of exactly 12 Da. The values for other atoms are calculated according to their masses relative to carbon-12. The molecular mass of a compound is worked out simply by adding together the masses of its constituent atoms.
because the sugar units that they contain can be released from the polymers and broken down further in order to generate chemical energy. The second role of polysaccharides is structural. Cellulose, which gives plant cells their rigidity, is a type of polysaccharide (Fig. 1.5), as is chitin, which forms part of the exoskeleton of insects and of animals such as crabs and lobsters. As well as polysaccharides, there are three other classes of large biomolecule that are important in biochemistry. The first of these is proteins, which are unbranched polymers of amino acids. Proteins play an immense range of roles in living organisms and most enzymes, which catalyze biochemical reactions, are proteins. Alphaamylase, which catalyzes the chemical reaction responsible for the release of glucose units from starch, is an example of an enzyme. Another is thrombin, which catalyzes the reaction that converts fibrinogen (itself a protein) into insoluble polymers of fibrin, which bind together as part of the blood clotting process (Fig. 1.6). The third type of large biomolecule is nucleic acid, of which there are two types, deoxyribonucleic acid or DNA and ribonucleic acid or RNA. DNA is present in chromosomes and contains biological information. In other words, genes are made of DNA. RNA is involved in the way in which the information contained in DNA is read by the cell. Finally, there are the lipids, a diverse group of large biomolecules which, like polysaccharides, have structural roles and act as energy stores, but which also have a number of other functions including regulatory ones – several hormones are lipids. Understanding the structures and functions of these four types of biomolecule will be the objective of Chapters 3–6 dealing, in turn, with proteins, nucleic acids, lipids and carbohydrates, the last of these being the type of biochemical that includes polysaccharides.
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Figure 1.5 The structural role of cellulose in a plant cell wall. Cellulose molecules line up and attach to one another, producing microfibrils which in turn form a network that gives the plant cell wall its rigidity.
cellulose fibers in cell wall
cellulose molecules glucose monomer OH O
hydrogen bonds between cellulose molecules O
CH2OH O OH
CH2OH O OH
CH2OH OH O
CH2OH O OH
Figure 1.6 The roles of thrombin, fibrinogen and fibrin in the formation of a blood clot. (A) Thrombin catalyzes a biochemical reaction that modifies the structure of fibrinogen, converting it to fibrin. Fibrin molecules then attach to one another to form polymers. (B) The fibrin polymers form a network over a rupture in a blood vessel, entrapping blood cells. This structure forms the blood clot.
1.1.4 Biochemistry is also the study of metabolism Living organisms, and the cells they comprise, are dynamic structures. This means that they require energy to power their various activities, and must also be able to synthesize new biomolecules as and when these are needed. These are the processes that constitute ‘life’. The fundamental principle of biochemistry is that these ‘life processes’ are chemical reactions. There are a great many of them, and they are linked together in complicated pathways (Fig. 1.7), but by studying the reactions individually it is possible to build up an understanding of the molecular basis of life. This will be our goal in Part II. Any chemical reaction can occur spontaneously, but its rate might be very slow. When chemical reactions are carried out in a test tube, a catalyst is often added to Figure 1.7 The metabolic pathways of a typical animal cell. Each dot represents a different biochemical compound. The lines indicate the steps in the network, each of these steps resulting in conversion of one compound into another. Copyright 2014 from Essential Cell Biology, 4th edition by Alberts et al. Reproduced by permission of Garland Science/Taylor & Francis LLC.
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speed up the reaction. An example is the use of vanadium oxide in the industrial production of sulfuric acid, from sulfur dioxide and oxygen, by the Contact Process (Fig. 1.8). The reaction rate is increased because the two gaseous reactants (sulfur dioxide and oxygen) become absorbed on the surface of the catalyst, bringing the molecules close together and promoting their combination to form sulfur trioxide, which reacts with water to give sulfuric acid. Biological reactions also make use of catalysts, but these are not metals. They are called enzymes and the vast majority are protein molecules, though a few made of RNA are also known. We will discover how enzymes act as catalysts in Chapter 7. Figure 1.8 The role of a catalyst. In the Contact Process, sulfur dioxide and oxygen are passed through layers of vanadium oxide particles. The two gases become absorbed to the surface of the particles, promoting their combination to form sulfur trioxide. The vanadium oxide catalyzes the reaction, but is not itself used up during the process.
Metabolism is the word used to describe the chemical reactions that occur in living organisms. These reactions are traditionally divided into two broad groups: •• catabolism – this is the part of metabolism that is devoted to the breakdown of compounds in order to generate energy •• anabolism – this refers to those biochemical reactions that build up larger molecules from smaller ones. We will study the central energy-generating processes of the cell, called glycolysis, the TCA cycle and the electron transport chain, in Chapters 8 and 9. A special type of energy generation, from sunlight by photosynthesis, will be the focus of Chapter 10. In Chapters 11–13 we will examine the metabolic pathways that result in the synthesis and breakdown of carbohydrates, lipids, and nitrogen-containing biochemicals, the latter including the monomeric components of proteins and nucleic acids. During these chapters, we will also ask how the various metabolic reactions occurring in living cells are regulated. Biochemical reactions do not occur randomly. Individual reactions are carefully controlled so that those that work together in a metabolic pathway operate in a coordinated fashion, to ensure that the substrates for the pathway are converted efficiently into the final end product. The rate of product synthesis can be controlled, and possibly switched off entirely, or the pathway may be modified so that different substrates are used, depending on what is available. Some of the signals that exert control over metabolic pathways originate within the cell in which the pathway is occurring, and others come from outside the cell. The signals might be very specific, altering the rate of a single reaction in a lengthy pathway, or they might be more general, affecting several different pathways at the same time. We will look at these various events at the appropriate places in Chapters 8–13.
1.1.5 The storage and utilization of biological information is an important part of biochemistry One set of biochemical reactions, although strictly speaking a part of anabolism, are regarded as having such special features that they are usually considered separately
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from the metabolism of the cell. These reactions are the ones responsible for the synthesis of DNA, RNA and protein. Here biochemistry and genetics overlap, because the same reactions are responsible for the replication and utilization of the biological information that is contained in genes. This is the information that an organism needs in order to develop, reproduce and carry out all of its metabolic reactions. These are the central topics of modern genetics, and biochemistry is used to study them, as we will see in Part III of this book.
First we will examine how DNA molecules replicate, so that precise copies of every gene are made every time a cell divides or an organism reproduces. That will be the focus of Chapter 14. The next question we will address is how the biological information contained in the genes is made available to the cell. This process is called gene expression, and for all genes it begins with synthesis of an RNA molecule (Fig. 1.9). In Chapter 15 we will discover that, because DNA and RNA are very similar types of molecule, this step in gene expression, called transcription, is quite straightforward in chemical terms. We will also learn that the RNA molecules that are made by transcription fall into different groups based on their function. Among these groups is messenger RNA (mRNA), which directs synthesis of proteins by a process referred to as translation. Protein synthesis will be the subject of Chapter 16.
1.1.6 Biochemistry is an experimental science In Parts I–III we will learn the facts of biochemistry. In Part IV we will examine how those facts were discovered. Biochemistry is and always has been an experimental science, and one of the attractions of the subject for new students is the possibility of one day carrying out their own biochemical research projects. Throughout Parts I–III of this book we will refer to some of the key experiments that have built up our understanding of biochemistry. In Part IV we will look more specifically at the methods and research strategies that are used in the most active areas of modern biochemistry. The first of these topics is the analysis of large biomolecules, in particular proteins. This is an important area of research because of the role of proteins as enzymes. Working out the detailed structure of an enzyme is often the best way of understanding how that enzyme catalyzes its specific biochemical reaction, and how the enzyme activity, and hence the biochemical reaction, is regulated in response
Box 1.4 ‘Omes are collections of biomolecules The proteome – the collection of proteins in a cell or tissue – is just one of several sets of biomolecules that biochemists study. These collections are loosely referred to as ‘omes, specific examples being: •• the genome, which is the entire complement of DNA molecules in a cell, containing all the organism’s genes •• the transcriptome, which is the collection of RNA molecules in a cell or tissue; the name ‘transcriptome’ derives from the fact that RNA molecules are copies, or transcripts, of genes •• the lipidome is the total lipid content of a cell or tissue •• the glycome is the carbohydrate content.
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Finally, there is the metabolome, which has a more complex composition. The metabolome is the complete collection of metabolites present in a cell under a particular set of conditions. These metabolites are the substrates, products and intermediates of all of the catabolic and anabolic reactions that are occurring in the cell. The metabolome therefore reflects the cell’s biochemical activities. These activities are specified by the proteome, and are dependent to at least some extent on the compositions of the lipidome, glycome and transcriptome. The biochemistry of a cell can therefore be looked on as resulting from the interplay between its various ‘omes.
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to chemical signals from within and outside of the cell. Over the years, biochemists have developed sophisticated methods for studying protein structure, such as nuclear magnetic resonance (NMR) and X-ray crystallography. We will look at these techniques in Chapter 18. In Chapter 18 will we also examine the various methods used to characterize the proteome, the collection of proteins present in a cell or tissue. The composition of the proteome defines the biochemical capability of a cell and so proteomics, the methods used to identify the individual components of a proteome, is an important aspect of biochemical research. To complement our study of proteomics, we will end Chapter 18 with a brief look at the equivalent techniques used to catalog the lipid and carbohydrate contents of cells. The second set of biochemical research methods that we will examine are those used to study DNA and RNA molecules. Central to these is DNA sequencing, the technique used to determine the structures of genes and the organization of genes in DNA molecules. Sequencing is used to understand the nature of the genetic information possessed by an organism and the way in which it is expressed. A second important technique is DNA cloning, which is used to transfer genes from one species to another, and which enables important pharmaceutical proteins such as human insulin to be synthesized by genetically engineered microorganisms. These and other methods used to study DNA and RNA are described in Chapter 19.
Further reading Coley NG (2001) History of biochemistry. Encyclopedia of Life Sciences. Wiley Online Library DOI: 10.1038/npg.els.0003077. Dronamraju KR (1999) Erwin Schrödinger and the origins of molecular biology. Genetics 153, 1071–6. Hui D (2012) Food web: concept and applications. Nature Education Knowledge 3(12): 6. Hunter GK (2000) Vital Forces: the discovery of the molecular basis of life. Academic Press, London. An account of the history and development of biochemistry. Patti GJ, Yanes O and Sluzdak G (2012) Metabolomics: the apogee of the omics trilogy. Nature Reviews Molecular Cell Biology 13, 263–9. Springer MS, Stanhope MJ, Madsen O and de Jong WW (2004) Molecules consolidate the placental family tree. Trends in Ecology and Evolution 6, 430–8. Explains how comparisons of molecular structures are used to construct evolutionary trees.