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Biochemistry
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Major references
1) Biochemistry
Garrett & Grisham, 2nd or 3rd Edition (provided)
2) Principles of Biochemistry, Lehninger, Nelson & Cox, 3rd edition
3) Biochemistry, Stryer, 5th edition
LIN Shengcai;
E-mail: [email protected]
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Content
• Basic concepts of biochemistry
• Biochemistry as a chemical science
• Distinction between inanimate matter from
living organisms
• Biological molecules or biomolecules
– Macromolecules and building blocks
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Biochemistry as an interdisciplinary science
Biological forces
Dynamic cells
Water: the medium of life
What Is Biochemistry?
• Biochemistry seeks to describe the structure, organization, and
functions of living matter in molecular terms.
Roots (history) of Biochemistry
z
The present day biochemistry is the interweaving product of
historical traditions of biochemistry, cell biology, and genetics.
z
Friedrich Wohler’s successful synthesis of urea from ammonium
cyanate (1828)
z
Hans Buchner and Eduard Buchner’s discovery of in vitro
fermentation in 1897, quite by accident. They were interested in
manufacturing cell-free yeast extract for possible therapeutic use.
These extracts had to be preserved without anticeptics at the time,
and so they decided to try sucrose, a commonly used preservative
in kitchen chemistry. They obtained a startling result: sucrose was
rapidly fermented into alcohol by the yeast juice.
• The significance of this finding is that they demonstrated for the first
time fermentation could occur outside the cell. This was in contrast
to the accepted view of their day, as asserted by Louis Pasteur, that
fermentation was inextricably tied to living cells. The chance
discovery opened up modern biochemistry. Metabolism became
chemistry.
• Crystallization of urease by JB Sumner in 1925
• Cell Biology: Robert Hook’s observation of cells (1600’s);
• Walter Flemming’s discovery of chromosomes (1875), identified as
genetic material (1902)
• Genetics: Gregor Mendel’s suggestion of gene as the unit of
heredity (1800’s); Hershy and Chase’s demonstration of DNA as
the genetic material (1950’s); Watson/Crick’s double helix (1953)
Questions asked by biochemists
• What are
matter?
the chemical structures of the components of living
• How do the interactions of these components give rise to organized
supramolecular structures, cells, multicellular tissues, and
organisms?
• How does living matter extract energy from its surroundings in order
to remain alive?
• How does an organism store and transmit the information it needs
to grow and to reproduce itself accurately?
• What chemical changes accompany the reproduction, aging, and
death of cells and organisms?
• How are chemical reactions controlled inside living cells?
The search for the answers is the study of the chemistry of life.
Biochemistry as a multidisciplinary science
Biochemistry draws its major themes from
The major themes
The major themes:
1. Organic chemistry, which describes the properties of biomolecules;
2. Biophysics, which applies the techniques of physics to study the
structures of biomolecules;
3. Medical research, which increasingly seeks to understand disease
states in molecular terms;
4. Nutrition, which has illuminated metabolism by describing the
dietary requirements for maintenance of health;
5. Microbiology, which has shown that single-celled organisms and
viruses are ideally suited for studying many metabolic pathways
and regulatory mechanisms;
6. Physiology, which investigates life processes at the
tissue and
organism levels;
7. Cell biology, which describes the biochemical division
of labor and life processes within a cell;
8. Genetics, which describes mechanisms that give a
particular cell or organism its biochemical identity.
What distinguishes living organisms from inanimate
matter?
• Living organisms are composed of lifeless molecules, which
conform to all the physical and chemical laws that describe the
behavior of inanimate matter. Yet living organisms possess
extraordinary attributes not exhibited by any random collection of
molecules. Biological chemistry is to study the properties of
biomolecules that distinguish them from other collections of matter,
and then identify the principles that characterize all living
organisms.
What distinguishes living organisms from
inanimate objects?
1. Degree of complexity: thousands of different molecules make up
the intricate internal structures in a cell.
2. Living organisms extract, transform, and use energy from their
environment. The energy enables them to build and maintain their
intricate structure or to do work. In contrast, inanimate matter
does not absorb energy to do work; rather, it tends to decay towards
a more disordered state, and reaches equilibrium with its
surroundings.
3. Living organisms are not at equilibrium with their surroundings.
They use energy to concentrate ions from their surroundings, for
example.
--The absorption of ions is an active process and consumes
energy.
4. A living organism is an open system
5. A closed system: If the system exchanges neither matter nor
energy with its surroundings, it is said to be closed.
6. An open system: it exchanges both energy and material with its
surroundings. Living organisms use either of two strategies to
derive energy from their surroundings:
(1) they take up chemical fuels from the environment and extract
energy by oxidizing them; or
(2) they absorb energy from sunlight.
7. The capacity for precise self-replication and self-assembly—the
quintessence of the living state.
--Billions of daughter cells can carry a faithful copy of the genetic
material of their parental cell. This replication is not quite like what
Schrodinger believed in his “What Is Life”.
Essence of life: “Life is for life”
• Each component of a living organism has a specific function. This is
true not only of macroscopic structures, such as leaves and stems
or hearts and lungs, but also of microscopic intracellular structures
such as the nucleus or chloroplast and of individual chemical
compounds. The interplay among the chemical components of a
living organism is dynamic; changes in one component cause
coordinating or compensating changes in another, with the whole
ensemble displaying a character beyond that of its individual
constituents. The collection of molecules carries out a program, the
end result of which is reproduction of the program and
self-perpetuation of that collection of molecules; in short,
life.--Lehninger
Bioenergetics
A living organism must work to stay alive and reproduce themselves,
which consumes energy. This comes to “bioenergetics”.
Bioenergetics is about energy transformation and exchange. The
central issue is the means by which energy from fuel metabolism is
coupled to energy-requiring reactions.
The major energy source adenosine triphosphate ATP
Activation energy
The activation energy of a chemical reaction is the energy
required to convert the reactant to transition state, which
gives rise to product(s). In other words, it is the energy
required to overcome the activation barrier.
ΔG is the free energy change between the reactants and
products.
Free energy changes
The molecular logic of life
The molecular logic is the bio-molecular language that describes
living processes in molecular terms. That is to say: we have to
understand amino acids first in order to understand proteins and
then protein complexes, protein structural motifs to understand
protein functions, nucleotides to DNA and its replication;
carbohydrates to polysaccharides, etc.
Diversity in biomolecules
Biological Molecules (I): DNA
Deoxyribonucleotides (DNA)
Chromatin
Histones vs Nonhistone
Histones are small, very basic proteins rich in lysine and arginine.
The histones are the basic building blocks of chromatin structure.
The nucleoids of prokaryotic cells also have proteins associated
with DNA, but these proteins are quite different from the histones
and do not seem to form a comparable chromatin structure.
Nonhistone chromosomal proteins - The histones are accompanied
by a much more diverse group of DNA-binding proteins called
nonhistone chromosomal proteins.
Chromosomes
Eukaryotic chromosome
Biological Molecules(II): Polysaccharides
Polysaccharide name
Glycogen
Cellulose
Chitin
Amylopectin
(starch)
Amylose (starch)
Monomeric Unit
D-Glucose
D-Glucose
N-Acetyl-D-glucosamine
D-Glucose (branched)
D-Glucose (linear)
Glucose
• Glucose is a six carbon sugar which can provide a rapid source of
ATP energy via glycolysis. Glucose is stored in polymer form by
plants (starch) and animals (glycogen). Plants also have cellulose,
which is not used to store glucose, but rather provides structural
integrity to the cells. Glucose has an anomeric carbon, which can
exist in the α and β configurations.Glucose can exist in both the D
and L forms (though the D form predominates biologically).
Structure of Glucose
Polysaccharides
• Polysaccharides containing a single sugar, such as glucose, are
referred to as glucans. Others, which contain only mannose, are
called mannans. Still others, containing only xylose, are called
xylans.
• Another group of polysaccharides of importance are
heteropolysaccharides, derivatives of carbohydrates.
• Example of polymers: Cellulose
Biological Molecules (III): Proteins
Amino Acids
• Amino acids are organic acids containing an amine group. They are
the basic units of a protein. The most common amino acids are the
L-α-amino acids.
20 kinds of amino acids in our body
Two additional amino acids have been
identified
Peptide bonds
Beta-sheet
Example of polypeptide : IgG
Biological molecules (IV): Lipids
Cholesterol
Lipid-soluble vitamins
Chemical properties of biomolecules
z Chirality
z Bondings
z Forces
Chirality
Biological forces for biomolecular interactions
• In addition to covalent bonds, which hold atoms together to
form molecules, there are weak forces, intramolecular or
intermolecular.
1. hydrogen bonds
2. van der waals forces
3. ionic interactions
4. hydrophobic interactions
Covalent bond (e.g. peptide bond)
Hydrogen bonding: a weak electrostatic attraction between
electronegative atom and hydrogen covalently linked to an
electronegative atom
Dipole-dipole interaction
van der Waals forces are the result of induced electrical interactions
between closely approaching atoms. The positively charged nuclei are
attracted to negatively charged electrons of nearby atoms.
Weak, and do not have a fixed geometry compared to dipole-dipole
interaction.
H2O: the medium of life
Biological functions of water
• Because of its unique chemical and physical characteristics, water
plays several key roles in metabolic processes. It serves as a
solvent for many chemical compounds, a medium in which many
chemical reactions occur, even as a reactant or product in many
reactions.
• As water is diffusible through the semipermeable membrane, it is
critical for adjusting osmotic differences. Therefore, water can help
prevent cells (organisms) from burst (osmotic lysis). Temperature
adjustment, waste removal, lubrication for joints, etc..
Water, H2O
• Water is the most abundant substance in living systems, making up
70% or more of the weight of most organisms;
• Water has a higher boiling point and heat energy of vaporization
than most other common solvents.
• Water participates in many biological reactions (e.g. hydrolysis).
• The dipolar nature of water provides hydrogen bonding.
• Water as a solvent:
– uncharged but polar biomolecules such as sugar dissolve
readily in water because of the stabilizing effect of hydrogen
bonds between the hydroxyl or carbonyl oxygen and the polar
water molecules.
–
Water interacts electrostatically with charged solutes, such as
Na+Cl-