CH1 PDF
CH1 PDF
CH1 PDF
Introduction to Biochemistry
Next time you’re at the gym, think about the fact that all the cells in your body
are working together to achieve your goals. Your muscles would rapidly fail without
your liver sending out the sugar they need to contract. You could only last for a
few minutes without your heart pumping oxygen-containing blood throughout your
body. And without your brain sending signals to mastermind it all, you wouldn’t even
make it out of the locker room.
One of the goals of this course is to understand how all the body’s organs work
together during exercise. This is pretty complicated, as you can imagine, so before
we can understand this cooperation between organs, we have to first discuss the
building blocks of the organs, cells. We can reduce cells even further down to their
components, the basic biological building blocks called lipids, carbohydrates,
proteins, and nucleic acids. That’s what biochemistry is all about, trying to
understand the whole from its parts.
Chemistry Review
If you were to take biochemistry, you would first have to take a semester of
introductory biology and four semesters of chemistry. However, our goal in this
course is to learn just enough about biochemistry to understand what’s going on at
the cellular level when we exercise. Let’s first highlight some of the most
important concepts from all those chemistry courses that you (probably) haven’t
taken so that you can follow the rest of this chapter.
Figure 1.
different variety of atom is called an element, and chemists arrange these in the
periodic table of the elements (Figure 1). Not all the elements are represented
equally, either on Earth itself or inside cells. All life forms are based on the
element carbon (C), and they also contain relatively large amounts of hydrogen (H),
nitrogen (N), oxygen (O), calcium (Ca), phosphorus (P), and sulfur (S).
Atoms are made up of even smaller particles: positively charged protons,
negatively charged electrons, and neutral neutrons. The arrangement of these
subatomic particles puts the protons and neutrons together in a massive nucleus
with the much smaller electrons buzzing around in a cloud. Atoms have equal
numbers of protons and electrons, which means that the charges cancel and they
are electrically neutral.
Atoms can link together in different ways to form molecules, with the “glue”
that holds them together called chemical bonds. Chemical bonds are often shared
pairs of electrons. The arrangement of atoms in a molecule is called the structure,
and chemists have developed some shorthand ways of representing structures.
As an example, let’s look at the molecule ethanol, which contains two atoms of
carbon, six atoms of hydrogen, and one atom of oxygen. We can write a chemical
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formula for ethanol as C2H6O, where the subscripts reveal how many of each type
of atom is in a molecule. Usually, chemists would draw this molecule using a simple
depiction with symbols for the atoms and lines for bonds (Figure 2C). This type of
drawing can be further simplified by leaving out the explicit bonds between carbon
and hydrogen, since there are so many carbon-hydrogen bonds in biological
molecules (Figure 2D).
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Figure 2.5. Salt is made up of oppositely charged particles (ions) that attract each
other. When salt is put into water, the ions separate and interact with water, becoming
dissolved. This happens because each oxygen atom carries a slight negative charge and
each hydrogen atom carries a slight positive charge- meaning that water is a polar
molecule because of oxygen’s greater ability to hold onto the shared pair of electrons.
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or falls by more than about a half-pH unit, serious illness or death may occur. Excessive
acidity of the blood results in a condition called metabolic acidosis, which can occur during
kidney failure, uncontrolled diabetes, poisoning, and shock. The opposite of acidosis is
alkalosis, which results from excess base (alkali) in the body fluids.
Regulation of acid-base balance occurs in the lungs and kidneys by using a buffer
system that serves to minimize the effects of added acid or base. Blood buffering is
critical, particularly during periods of intense physical activity when lactic acid is
produced.
The Cell
Organisms are composed of one or more cells, the basic units of life. One of the
basic principals of biology is that cells only arise from other cells. That is why our
bodies contain reserves of stem cells, flexible precursor cells that can irreversibly
change into many different types of specialized cells. For example, all the
different blood cell types (red cells and the various types of white cells) are
replaced regularly, arising from a single type of stem cell in the bone marrow.
Scientists are actively investigating the potential of stem cells to grow into new
tissues to replace those damaged by injury or diseases like Alzheimer’s.
There are about 200 different kinds of cells in the human body, and each adult
human contains about 1013 cells all working together. Different types of cells
display a wide variety of shapes and sizes. Let’s focus on the key features found in
a “generic” animal cell (Figure 3). The cell is enclosed by the plasma membrane,
which forms the boundary that separates the cell from its environment. Only cells
of higher organisms, the eukaryotes, contain interior compartments called
organelles that are also enclosed by a membrane.
Key parts of a eukaryotic cell include the following:
• the nucleus, where the genetic material containing the information necessary
for the synthesis of all cellular molecules is found.
• the mitochondria, where fuels are oxidized for energy. On average each cell
contains hundreds of mitochondria.
• the cytosol, the watery solution of proteins, nutrients, and other molecules
in which the organelles are suspended.
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Lipids
Overview of Lipids Lipids are defined by their
solubility. They are not
Waxes, fats such as lard, and oils belong to the
soluble in water.
general class of biological molecules called lipids.
Although biological lipids are structurally quite diverse, none of them dissolve well
in water because they hydrophobic. Lipids play a number of key roles in the cell,
representing stored chemical energy, comprising the basic structural units of
membranes, and carrying signals between cells.
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Figure 4
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water and energy. We will examine how triglycerides are oxidized to release energy
when we consider energy production during metabolism.
Figure 6
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Figure 7
(Figure 8). This structure is very different from the phospholipids shown above
and provides rigidity to the membrane. Up to 25% of the lipids of some membranes
can be cholesterol. The single polar group of cholesterol is the –OH, which lines up
with the polar head groups of the phospholipids in a membrane. The rest of the
molecule inserts itself into the hydrophobic interior of the membrane. Other
steroids also play important biological roles, particularly in signaling. Familiar
examples include the sex hormones, estradiol and testosterone, which we will talk
about more later in the course.
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Monosaccharides
The building blocks of carbohydrates are the monosaccharides. Common
monosaccharides include glucose, blood sugar, and fructose, fruit sugar.
Monosaccharides can react with other monosaccharides to form disaccharides
(containing 2 monosaccharide units; Figure 9), oligosaccharides (3-19 units), and
polysaccharides (>20 units).
Polysaccharides
Polysaccharides that contain repeating units of glucose (glucose polymers) are
important energy storage and structural molecules in both plants and animals
(Table 1). Two important
glucose polymers are cellulose
and starch, which chemically
differ only in how the glucose
subunits are linked together
(Figure 10). Cellulose has the
bonds pointing up, and starch
has the bond pointing down.
Although this may seem like a
minor difference, the two are Figure 9. Joining the two monosaccharides
dramatically distinct. Cellulose, glucose and fructose leads to the
the principal component of disaccharide sucrose , common table sugar.
wood, is water-insoluble and indigestible (to animals). About a third of all plant
matter is cellulose: it provides the scaffolding that holds up most plants, giving
rigidity to their cells. On the other hand, starch, which is made by plants to store
energy for future use, is an easily digestible compound widely enjoyed in potatoes,
pasta, and bread. Humans make a similar molecule for energy storage called
glycogen. Cellulose and starch illustrate the principle that structure affects
function in biological systems.
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Figure 10. Starch and cellulose are both polymers of glucose. They differ only in
whether the connecting oxygen atom points down as in starch or up as in cellulose.
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Polypeptides
When many amino acids link together, a polypeptide is formed. Proteins consist
of one or more polypeptide chains. After a polypeptide chain is synthesized in the
cell, it folds into a unique three-dimensional shape (Figure 14). Folding is guided by
such forces as “like dissolves like” with hydrophobic amino acids typically
interacting with other hydrophobic amino acids in the interior and polar amino acids
interacting with water on the exterior.
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Enzymes
Thousands of chemical reactions must occur in Enzymes act as catalysts,
a typical cell in order to maintain life. Many of increasing the rate of a
reaction of a substrate without
these reactions would occur much too slowly
being consumed themselves.
without the aid of protein catalysts called
enzymes, which can lead to rate enhancements of up to 1017. Note that a rate
enhancement of 1017 means that a reaction that takes one second in the presence
of an enzyme would take over 3 billion years without the enzyme.
An enzyme is specific for a particular target molecule, called the substrate,
much as a key fits only a certain lock. Again, the three-dimensional structure of
the protein is crucial for its function. Through a variety of chemical strategies,
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Fig 16
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Antibodies
The action of the immune system is mediated by another class of proteins called
antibodies. Antibodies are composed of four polypeptide chains, two “heavy” chains
and two “light” chains, which interact to form a Υ-shaped structure (Figure 17).
Antibodies bind to specific molecules called antigens, which are often part of
disease-causing microorganisms. Specificity arises from the amino acids at the tips
of the Υ, which differ between antibodies and are therefore called the “variable”
regions. Rather than inducing their antigens to undergo chemical reactions like
enzymes, antibody binding triggers a massive immune response that results in
annihilation of the invader.
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Antibody responses are vital to help us fight infectious disease but can have
disastrous consequences, as in the case of the rejection of blood of the wrong
type. Specific carbohydrates on the surface of red cells determine blood type.
These carbohydrates also act as antigens for specific antibodies found in people
with other blood types. For example, people with type A blood have the A antigen
on the surface of their red cells and antibodies in their bloodstream against the
type B antigen. If type B blood is injected into a person with type A blood, these
antibodies will perceive the type B blood cells as invaders and target them for
destruction by the immune system. Additionally, antibody binding to the B-antigens
triggers clumping of the foreign cells into an insoluble mass, a process called
agglutination (Figure 18). Serious consequences may result for the patient,
including shock, kidney failure, and death.
Before blood types were discovered in 1900, doctors experimented with blood
transfusions in patients dying from severe blood loss, often transferring blood
directly from a healthy donor. Sometimes these treatments saved lives and other
times they hastened death when the blood was of the wrong type. Discovery of
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ABO blood types was a key step in the ability to use transfusions routinely in
medical procedures.
The agglutination reaction is now used to determine blood type. Specific
antibodies are added to a sample of blood. The antibody that clumps the cells
together to form a solid that falls out of solution (a precipitate) reveals the blood
type. Before receiving a transfusion today, a patient’s blood is routinely typed to
avoid problems with blood incompatibility.
Structural Proteins
Proteins also play a variety of structural roles. Muscle, hair, skin, and connective
tissue are largely comprised of proteins with three-dimensional structures well
suited for their functions. Amazingly, the same protein, keratin, comprises not only
hair and skin but also wool, nails, claws, quills, horns, and hoofs. The degree of
hardness of the resulting material is dependent on the number of covalent linkages
involving the amino acid cysteine. Two cysteines form an S-S covalent bond (a
disulfide linkage) that links keratin strands together to form multi-stranded
fibers. In the toughest keratin filaments, such as those comprising rhinoceros
horn, almost one in five amino acids is a cysteine involved in a disulfide linkage.
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Figure 19. Left: The presence of a single hydrophobic amino acid on the surface of
hemoglobin (top) results in individual molecules clumping together (middle), eventually
forming long, insoluble fibers (bottom). Right: The result is “sickling” of red cells to an
elongated shape that can lead to painful “log jams” in blood vessels.
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Nucleic Acids
Overview of Nucleic Acids
The instructions to assemble each protein in DNA is the genetic material.
the cell can be found in the genetic material, We inherit 23 chromosomes
comprised of the nucleic acids, DNA and RNA. from each parent.
Deoxyribonucleic acid (DNA) is the carrier of
genetic information, while ribonucleic acid (RNA) plays a role in using the
information contained within the DNA to make new molecules in the cell. Some
viruses use RNA as their genetic material instead of DNA.
DNA and RNA are both polymers of nucleotide subunits (Figure 20) linked by
phosphate groups to form long chains. Inside the nucleus, DNA interacts with
proteins for tight packaging so that the 3-meter long chains can fit inside such a
small space (Figure 21). With few exceptions, each cell in the human body contains
3 billion nucleotide units assembled into nuclear DNA. Mitochondria also contain
their own DNA, which is present as a circular molecule of about 17,000 nucleotide
units.
Fig 20
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Fig 21
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Figure 22. In the process of transcription, the sequence of one of the DNA strands
(the gene) is “read” by the cellular machinery to create a new messenger RNA (mRNA)
molecule. The mRNA is “complementary” to the DNA in the same way that the two DNA
strands are complementary to each other. For example, if the coding strand has a G,
then the mRNA has a C. Because RNA uses U instead of T, an A in the DNA becomes a
U in the mRNA. In the process of translation, the sequence of the mRNA is interpreted
by the ribosome in three base units as a specific amino acid. The ribosome links each
successive amino acid to the growing chain.
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