Download Chapter 1: Biochemistry in the Modern World

Chapter 1
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.
1.1
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’.
01 Biochemistry Chap01 cpp.indd 1
28/04/2016 06:57
2 | Ch a p ter 1 | Biochemistry in the modern world Table 1.1. The elemental
composition of the average adult
human
Element
Amount in a 70 kg human
Oxygen
43 kg (61%)
Carbon
16 kg (23%)
Hydrogen
7 kg (10%)
Nitrogen
1.8 kg (2.5%)
Calcium
1.0 kg (1.4%)
Phosphorus
780 g (1.1%)
Potassium
140 g (0.20%)
Sulfur
140 g (0.20%)
Sodium
100 g (0.14%)
Chlorine
95 g (0.14%)
Magnesium
19 g (0.03%)
Iron
4.2 g
Fluorine
2.6 g
Zinc
2.3 g
Silicon
1.0 g
Rubidium
0.68 g
Strontium
0.32 g
Bromine
0.26 g
Lead
0.12 g
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’.
01 Biochemistry Chap01 cpp.indd 2
28/04/2016 06:57
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
01 Biochemistry Chap01 cpp.indd 3
28/04/2016 06:57
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.
lion
carnivores
herbivores
cheetah
giraffe
hyena
Thomson’s
gazelle
primary
producers
acacia
impala
zebra
wildebeest
grass
BIOCHEMISTRY | Chapter 01 | Figure 02
© scion publishing ltd | design by www.blink.biz
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.
kangaroo
sheep and goats
cattle
pigs
horses
dogs
cats
rabbits
rats
mice
New World monkeys
Old World monkeys
orang-utan
gorilla
chimpanzee
human
BIOCHEMISTRY | Chapter 01 | Figure 03
© scion publishing ltd | design by www.blink.biz
01 Biochemistry Chap01 cpp.indd 4
28/04/2016 06:57
1.1 | What is b io c hemis tr y? | 5
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.
1780sAntoine 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.
1811–1823Michel 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.
1827Hans Fischer synthesized porphyrins and showed
that these compounds bind oxygen in red blood
cells.
1833Anselm 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.
1877Moritz Traube suggested that enzymes are a
type of protein.
1880–1900Emil 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.
1895–1900The 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.
01 Biochemistry Chap01 cpp.indd 5
28/04/2016 06:57
6 | Ch a p ter 1 | Biochemistry in the modern world
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
1.1.3
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.
monomers
Figure
1.4 A linear
polymer.
BIOCHEMISTRY
| Chapter
01 | Figure 04
© scion publishing ltd | design by www.blink.biz
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
01 Biochemistry Chap01 cpp.indd 6
28/04/2016 06:57
1.1 | What is b io c hemis tr y? | 7
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
BIOCHEMISTRY | Chapter 01 | Box 1-3| Figure 01
Although the
number of protons is invariant, different atoms of
© scion publishing ltd | design by www.blink.biz
the same element can have different numbers of neutrons. These
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.
01 Biochemistry Chap01 cpp.indd 7
28/04/2016 06:57
8 | Ch a p ter 1 | Biochemistry in the modern world 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
plant
cells
cellulose
macrofibril
cellulose
microfibril
cell wall
cellulose
molecules
glucose
monomer
OH
O
OH
O
hydrogen bonds between
cellulose molecules
O
O
OH
OH
O
O
OH
O
OH
O
OH
O
OH
CH2OH
O
OH
OH
O
O
CH2OH
O
OH
CH2OH
OH
O
OH
O
OH
CH2OH
OH
O
OH
CH2OH
CH2OH
O
OH
CH2OH
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.
O
O
CH2OH
OH
OH
CH2OH
O
OH
CH2OH
BIOCHEMISTRY | Chapter 01 | Figure 05
© scion publishing ltd | design by www.blink.biz
A. conversion of fibrinogen to a fibrin polymer
fibrinogen
thrombin
fibrin monomer
fibrin dimer
fibrin polymer
B. a blood clot
fibrin
blood vessel wall
BIOCHEMISTRY | Chapter 01 | Figure 06
© scion publishing ltd | design by www.blink.biz
01 Biochemistry Chap01 cpp.indd 8
28/04/2016 06:57
1.1 | What is b io c hemis tr y? | 9
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.
BIOCHEMISTRY | Chapter 01 | Figure 07
© scion publishing ltd | design by www.blink.biz
01 Biochemistry Chap01 cpp.indd 9
28/04/2016 06:57
10 | Ch a p ter 1 | Biochemistry in the modern world 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.
sulfur
vanadium oxide catalyst
sulfur dioxide
+
oxygen
air
sulfur trioxide
furnace
converter
BIOCHEMISTRY | Chapter 01 | Figure 08
© scion publishing ltd | design by www.blink.biz
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.
1.1.5The 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
01 Biochemistry Chap01 cpp.indd 10
28/04/2016 06:57
1.1 | What is b io c hemis tr y? | 11
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.
DNA
transcription
RNA
translation
protein
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.
Not all of the genes in a cell are active all the time. Many are silent for long periods,
Figure 1.9 Gene
expression.
BIOCHEMISTRY
| Chapter
01 | Figure 09
©
scion
publishing
| designisby
www.blink.biz only being converted into RNA and protein on those particular occasions when their
The
DNA
copy ofltd
a gene
transcribed
into an RNA molecule. For proteinproducts are needed. All organisms are therefore able to regulate expression of their
coding genes, the RNA is then
genes, so that those whose RNA or protein products are not required at a particular
translated into the protein.
time are switched off. We will study the great variety of processes by which gene
expression can be controlled in Chapter 17.
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.
01 Biochemistry Chap01 cpp.indd 11
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.
28/04/2016 06:57
12 | Ch a p ter 1 | Biochemistry in the modern world 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.
01 Biochemistry Chap01 cpp.indd 12
28/04/2016 06:57