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Physical Foundations
and
Genetic Foundation
2310310 Foundations of Biochemistry
Piamsook Pongsawasdi
Kanoktip Packdibamrung
August 2016
Living Organisms Exist in a Dynamic Steady State
 They are never at equilibrium with their surroundings
 Molecules and ions within living organism are different in
kinds and concentration from those in the surroundings
 Constant characteristic composition at maturity but
population changes
 Continuous synthesis and breaking down of small
molecules, macromolecules, and supramolecular
complexes, therefore maintaining a constant
concentration – Dynamic Steady State
 Involve constant flux of mass and energy through
the system
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Living Organisms Need Energy
 A living organism is an open system
 Exchanges both matter and energy with its surroundings
 Extract, channel and consume energy
 Organisms derive energy in two ways
 Take up chemical fuels (e.g. glucose) from the environment and
extract energy by oxidizing them
 Absorb energy from sunlight
 1st Law of Thermodynamics: Energy Conservation
In any physical or chemical change, the total amount of energy in the
universe remains constant, although the form of the energy may change
 Cells are consummate transducer of energy, capable of inter-
converting chemical, electromagnetic, and osmotic energy with great
efficiency
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Energy Conversion
(a) Energy extracted from surroundings
(b) Energy conversion to produce work
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Energy Conversion
(c) Return energy
to surroundings
(d) Release
end-products
(e) Macromolecule
formation
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Entropy – Randomness & Disorder
Oxidation of Glucose
C6H12O6 + 6O2
6CO2 + 6H2O
 Increase in number of molecules, solid changes into
liquid and gas
more freedom of movement,
more molecular disorder, entropy increases
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The Flow of Electrons Provides Energy
 All energy transduction in cells can be traced to a flow of
electrons from one molecule to another, in a downhill flow
from higher to lower electrochemical potential
 Photosynthetic cells absorb the sun's radiant energy and
use it to drive electrons from water to carbon dioxide, forming
energy-rich products such as starch and sucrose
6CO2 + 6H2O
Light
energy
C6H12O6 + 6O2
Light-driven
reduction of CO2
 Non-photosynthetic organisms obtain energy by oxidizing
the energy-rich products of photosynthesis, passing electrons
to atmospheric oxygen to form water, carbon dioxide, and
other end products, which are recycled in the environment.
C6H12O6 + 6O2
6CO2 + 6H2O
Energy-yielding
oxidation of glucose
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Creating & Maintaining Order Requires Energy
 Energy is required for formation of covalent bond
between monomeric subunits and for ordering subunits
into correct sequence of macromolecules
 According to 2nd law of Thermodynamics:
the total entropy of the universe is continually increasing
 To synthesize macromolecules, free energy must be
supplied to the cells
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Energy Changes during Chemical Reaction

When a chemical reaction occurs at constant temperature
(T in Kelvin) :
G = H – TS
Free energy change
Enthalpy change
Entropy change
numbers and kinds of chemical bonds
and non-covalent interaction broken and formed
H is –ve for a reaction that releases energy
S is +ve for a reaction that increases the system’s randomness
G is –ve for a spontaneous reaction (exergonic)
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Coupled Biological Reactions
 A process occurs spontaneously if G is –ve
(free energy released – exergonic )
 For energy requiring reactions (endergonic), cells couple them
with other exergonic reactions to make sum of G –ve
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Keq and Go
 Both measure reaction tendency to proceed
spontaneously
 If high equilibrium constant Keq,, the reaction proceeds
until almost reactants converted to products
 Free energy G – a measure of the distance of
a system from its equilibrium position
 Standard free energy change, Go, a constant
characteristic for each reaction
 From Gibbs:
G = Go + RT ln Keq
At equilibrium, G = 0, then Go = – RT ln Keq
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Enzymes – Biological Catalysts
 Enhance the rate of specific reactions without being
consumed in the process
 Change of reactants (substrates) to products
 Distortion of substrate’s existing bonds create a transition
state (TS) of higher free energy
 Energy difference between reactant in its ground state
and in its TS = G‡ (activation energy)
 Binding of E to TS is exergonic; energy released by
binding reduces G‡ and increases the reaction rate
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Release of Ordered Water Favors Formation of
an Enzyme-Substrate Complex
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Pathways
 Enzyme-catalyzed reactions are organized into many sequences
of consecutive reactions (pathways)
 Catabolism: degradative pathways - change organic nutrients
into simple end products and release chemical energy to drive
the synthesis of ATP
 Anabolism: synthetic pathways – change small precursors to
larger and more complex molecules
 Metabolism: overall network of enzyme-catalyzed pathways,
interconnected and interdependent, regulated to achieve
balance and economy (save energy)
 Pathways acting on the main constituents of cells (proteins, fats,
sugars and nucleic acids) are identical in all living organisms
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Central Roles of
ATP and NAD(P)H
 ATP links energy releasing
(exergonic) and energy
consuming (endergonic)
cellular processes
 Cofactor - NAD(P)+ - collects
electrons from oxidative
reactions
NAD(P)H which
donates electrons in reduction
reactions in biosynthesis
* Nicotinamide adenine dinucleotide phosphate
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Summary – Physical Foundations (1)
 Living cells are open systems, exchanging matter and
energy with their surroundings, extracting and channeling
energy to maintain themselves in a dynamic state, distant
from equilibrium
 Energy is obtained from sunlight or fuels by converting the
energy from electron flow into the chemical bonds of ATP
 The tendency for a chemical reaction to proceed toward
equilibrium can be expressed as the free energy change,
G, which = H – TS
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Summary – Physical Foundations (2)
 When G of a reaction is –ve, the reaction is exergonic
and tends to go toward completion; when it is +ve,
the reaction is endergonic and tends to go in the reverse
direction. When 2 reactions are summed, the overall G is
the sum of G of 2 separate reactions.
 The reactions converting ATP to Pi + ADP or to AMP + PPi
are highly exergonic.
 Many endergonic cellular reactions are driven by coupling
them, through a common intermediate to these highly
exergonic reactions.
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Summary – Physical Foundations (3)
 The standard free-energy change, Go, is related to the
equilibrium constant: Go = – RT ln Keq
 Most cellular reactions proceed at useful rates via enzyme
catalysis. Enzymes act by stabilizing the transition state,
reducing the activation energy, G‡ and increasing the
reaction rate.
 Metabolism - interconnected reaction sequences that
interconvert cellular metabolites. Each sequence is
regulated to provide what the cell needs at a given time
and to expend energy only when necessary.
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Genetic Foundations
 Living cells and organisms can reproduce themselves
for countless generations
 Continuity of inherited traits implies constancy in the
structure of molecules containing genetic information
 DNA - sequence of deoxyribonuclotide subunits encodes
the instructions for forming all other cellular components
 Effective storage, expression and reproduction of genetic
messages define individual biological species
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Complementarity in Double-stranded DNA
 DNA – linear polymer of covalently
joined deoxyribonucleotides
 Deoxyadenylate (A)
 Deoxyguanylate (G)
 Deoxycytidylate (C)
 Deoxythymidylate (T)
 Two complementary strands held
together by hydrogen bond between
A – T, G – C
 Twist about each other to form DNA
double helix
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Fidelity of DNA Replication
 Two DNA strands separate
 Each serves as a template
for synthesis of a new
complementary strand
 Generating two identical
double helical molecules,
one for each daughter cell
 If one strand is damaged,
the other strand acts as a
template for repair of the
damage
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Concept of
Central dogma
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From 1- to 3-Dimensions
 Expression of linear sequence of deoxyribonucleotide subunits
in DNA
mRNA
sequence of amino acids)
protein (corresponding linear
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From 1-D to 3-D
 Protein folds into particular 3-D shape,
stabilized primarily by non-covalent interaction
 Precise 3-D structure “native conformation”
is important for its function
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Summary – Genetic Foundations
 Genetic information is encoded in the linear sequence of
4 types of deoxyribonucleotides in DNA
 The double-helical DNA molecule contains an internal
template for its own replication and repair
 The linear sequence of amino acids in a protein, which is
encoded in the DNA of the gene for that protein, produces
a protein’s unique 3-D structure – a process also
dependent on environmental conditions
 Individual macromolecules with specific affinity for other
macromolecules self-assemble into supramolecular
complexes
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