Bioenergetics
Dr. Nafeesa Qudsia Hanif
Organisms can be classified
according to their source of
energy (sunlight or oxidizable
chemical compounds) and
their source of carbon for the
synthesis of cellular material.
Metabolism Is the Sum of Cellular
Reactions
• Metabolism - the entire network of chemical
reactions carried out by living cells
• Metabolites - small molecule intermediates in
the degradation and synthesis of polymers
• Catabolic reactions - degrade molecules to
create smaller molecules and energy
• Anabolic reactions - synthesize molecules for
cell maintenance, growth and reproduction
Major Pathways in Cells
• Metabolic fuels
Three major nutrients consumed by mammals:
(1) Carbohydrates - provide energy
(2) Proteins - provide amino acids for protein
synthesis and some energy
(3) Fats - triacylglycerols provide energy and
also lipids for membrane synthesis
Overview of
catabolic pathways
Nucleophiles:
functional groups
rich in electrons and
capable of donating
them
Electrophiles:
electron-deficient
functional groups
that seek electrons
The relative
electronegativities:
F>O>N>C=S>P=H
Cleavage of a C-C or C-H bond
Carbon-carbon bond formation reactions
Oxidation-reduction reactions
13.1 Bioenergetics and
Thermodynamics
Biological Energy transformations
obey the Laws of Thermodynamics
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For any physical or chemical change, the total amount of
energy in the universe remains constant; but it cannot be
created or destroyed.
The universe always tends toward increasing disorder: in all
natural processes, the entropy of the universe increases.
Living cells and organisms are open system, exchanging both
material and energy with their surroundings;
living systems are never at equilibrium with their surrounding,
and the constant transactions between system and
surrounding explain how organisms can create order within
themselves while operating within the second law of the
thermodynamics.
13.1 Bioenergetics and Thermodynamics
A. Free-Energy Change
• Free-energy change (DG) is a measure of the
chemical energy available from a reaction
DG = Gproducts - Greactants
• DH = change in enthalpy
• DS = change in entropy
Relationship between energy and
entropy
• Both entropy and enthalpy contribute to DG
DG = DH - TDS
(T = degrees Kelvin)
-DG = a spontaneous reaction in the
direction written
+DG = the reaction is not spontaneous
DG = 0 the reaction is at equilibrium
Standard Free-Energy Change
(DGo)
• Reaction free-energy depends upon conditions
• Standard state (DGo) - defined reference conditions
Standard Temperature = 298K (25oC)
Standard Pressure = 1 atmosphere
Standard Solute Concentration = 1.0M
• Standard transformed constant = DGo’
Standard H+ concentration = 10-7 (pH = 7.0)
H2O concentration = 55.5 M
Mg2+ concentration = 1 mM
Equilibrium Constants and
Standard Free-Energy Change
• For the reaction: aA + bB
cC + dD
DGreaction = DGo’reaction + RT ln([C]c[D]d/[A]a[B]b)
• At equilibrium: Keq = [C][D]/[A][B] and
DGreaction = 0, so that:
DGo’reaction = -RT ln Keq
The standard free-energy change is
directly related to the equilibrium
constant
Energy coupling in mechanical and
chemical processes. (a) The downward
motion of an object releases potential
energy that can do mechanical work. The
potential energy made available by
spontaneous downward motion, an
exergonic process (pink), can be coupled
to the endergonic upward movement of
another object (blue). (b) In reaction 1, the
formation of glucose 6-phosphate from
glucose and inorganic phosphate (Pi)
yields a product of higher energy than the
two reactants. For this endergonic reaction,
△G is positive. In reaction 2, the
exergonic breakdown of adenosine
triphosphate (ATP) can drive an
endergonic reaction when the two
reactions are coupled. The exergonic
reaction has a large, negative free-energy
change (△G2), and the endergonic
reaction has a smaller, positive freeenergy change (△G1). The third reaction
accomplishes the sum of reactions 1 and 2,
and the free-energy change, △G3, is the
arithmetic sum of _G1 and △G2. Because
△G3 is negative, the overall reaction is
exergonic and proceeds spontaneously.
Standard free-energy changes
are additive
Equilibrium constants are
multiplicative
13.2 Phosphoryl Group
Transfers and ATP
• Single-step vs multistep pathways
• A multistep enzyme
pathway releases
energy in smaller
amounts that can be
used by the cell
The Free Energy of ATP
• Energy from oxidation of metabolic fuels is
largely recovered in the form of ATP
Hydrolysis of ATP
electrostatic repulsing
solvation
• Hydrolysis, by causing
charge separation
(relieves electrostatic
repulsing)
• Pi is stabilized by
formation of a
resonance hybrid
(same degree of double
bound)
• ADP2- immediately
ionizes, releasing a
proton into a medium of
very low (H+).
• Greater degree of
solvation of the
products Pi and ADP
relative to ATP.
Hydrolysis of ATP
Phosphorylation potential
Mg2+ and ATP
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Forming of Mg2+ complexes partially shields the negative charges
and influences the conformation of the phosphate groups in
nucleotides such as ATP and ADP.
Hydrolysis of phosphoenolpyruvate
(PEP)
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Catalyzed by pyruvate kinase, this reaction is followed by
spontaneous tautomerization of the product, pyruvate,
tautomerization is not possible in PEP, and thus the products
of hydrolysis are stabilized relative to reactants. Resonance
stabilization of Pi also occurs.
Hydrolysis of 1, 3-bisphosphoglycerate
• The direct product of hydrolysis is 3-phosphoglyceric acid, which has an
un -dissociated carboxylic acid group, but dissociation occurs
immediately. This ionization and the resonance structures, it makes
possible stabilize the product relative to the reactants.
• Resonance stabilization of Pi further contributes to the negative freeenergy change.
Hydrolysis of
phosphocreatine
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Breakage of the P-N bond in phosphocreatine
produces creatine, which is stabilized by formation of
a resonance hybrid.
Phosphagens: Energy-rich storage
molecules in animal muscle
• Phosphocreatine (PC) and phosphoarginine (PA)
are phosphoamides
• Have higher group-transfer potentials than ATP
• Produced in muscle during times of ample ATP
• Used to replenish ATP when needed via creatine
kinase reaction
Thioesters---Hydrolysis of
acetyl-coenzyme A
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Acetyl-CoA is a
thioester with a large,
negative, standard free
energy of hydrolysis.
Thioesters contain a
sulfur atom in the
position occupied by an
oxygen atom in oxygen
esters.
Free energy of hydrolysis for
thioesters and oxygen esters
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The products of both type of hydrolysis reaction have about
the same free-energy content (G). Orbital overlap between
the O and C atoms allows resonance stabilization in oxygen
esters.
transfers, Not by simple hydrolysis --in two steps
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A phosphoryl group is first
transferred from ATP to
glutamate
The phosphoryl group is
displaced by NH3 and
released as Pi
ATP can carry energy from
high-energy phosphate
compounds produced by
catabolism to compounds
such as glucose, converting
them into more reactive
species.
ATP thus serves as the
universal energy currency
in all living cells
Phosphoryl-Group Transfer
• Phosphoryl-group-transfer potential - the ability
of a compound to transfer its phosphoryl group
• Energy-rich or high-energy compounds have
group transfer potentials equal to or greater than
that of ATP
• Low-energy compounds have group transfer
potentials less than that of ATP
High-energy compounds have a DG’o of
hydrolysis more negative than -25
kJ/mol
- 25 kJ/mol
Nucleophilic displacement reaction of ATP (SN2
nucleophilic displacements: PP67)– ATP donates 1).
phosphoryl, 2). pyrophosphoryl, and 3). adenylyl
groups
ATP as energy currency in many biochemistry
reactions
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Inorganic pyrophosphatase hydrolyed the PPi to two Pi,
releasing 19 KJ/mol.
Activation of a fatty acid --- either for energy-yielding oxidation
or for use in the synthesis of more complex lipids: is attached
to the carrier coenzyme A.
Assembly of informational macromolecules – RNA .
ATP energizes active transport and muscle contraction.
Transphosphorylations between Nucleotides occur in all cell
type (NTP—NDP: Nucleoside diphosphate kinase or Adenylate
kinase or Creatine kinase,
Inorganic polyphosphate is a potential phosphoryl group donor
(polyphosphate kinase —energy reservoir)
Nucleoside diphosphate kinase
Adenylate kinase
Creatine kinase
Ping-Pong Mechanism of Nucleoside diphosphate
The enzyme binds its first substrate (ATP), and a phosphoryl
group is transferred to the side chain of a His residue. ADP
departs, and another nucleoside diphosphate replace it, and
this is converted to the corresponding triphosphate by transfer
of the phosphoryl group from the phosphohistidine residue.
Fire flashes: glowing reports of
ATP
• From chemical energy into light
energy.
• An pyrophosphate cleavage of ATP
to form luciferyl adenylate. In the
presence of O2 and luciferase, the
luciferin undergoes a multiple step
oxidative decarboxylation to
oxyluciferin and accompanied by
remission of light.
13.3 Biological OxidationReduction Reactions
Oxidation-reduction reactions
Conjugated redox pair: Fe2+ (electron donor), and Fe3+ (electron acceptor)
Biological oxidations
often involved
dehydrogenation
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The flow of electrons can do biological work.
O2 has a higher affinity of electrons—
exergonic reaction— electromotive force
(emf) provide energy to energy transducers
(enzymes and other proteins) that do
biological work.
When C share an electron pair with another
atom. The sharing is unequal in favor of the
more electronegative atom (H < C < S < N
< O).
Electrons transfer in 4 ways: as e; as
hydrogen atoms (H); as a hydride ion (H-);
and combination with oxygen.
Reducing equivalent --- a single electron
equivalent participating in an oxidationreduction reaction--- biological oxidations as
two reducing equivalents passing from
substrate to oxygen.
Reduced Coenzymes Conserve Energy
from Biological Oxidations
• Amino acids, monosaccharides and lipids are
oxidized in the catabolic pathways
• Oxidizing agent - accepts electrons, is reduced
• Reducing agent - loses electrons, is oxidized
• Oxidation of one molecule must be coupled with
the reduction of another molecule
Ared + Box
Aox + Bred
Free-Energy Change Is Related
to Reduction Potential
• The reduction potential of a reducing agent is a
measure of its thermodynamic reactivity
• The electromotive force is the measured
potential difference between two half-cells
• Standard reduction potential is for hydrogen:
Eo = H+ + e-
½ H2
Measurement of the standard reduction potential (E’o) of a redox pair
The ultimate reference half-cell is the
hydrogen electrode, at pH 0. The
electromotive force (emf) of this
electrode is designated 0.00 V. At pH
7 in the test cell, E for the hydrogen
electrode is 0.414 V.
Electrons tend to flow through the
external circuit from the half-cell of
lower standard reduction potential to
the half-cell of higher standard
reduction potential. By convention,
the half-cell with the stronger
tendency to acquire electrons is
assigned a positive value of E.
Actual reduction potentials (E)
• Under biological conditions, reactants are not
present at standard concentrations of 1 M
• Actual reduction potential (E) is dependent
upon the concentrations of reactants and
products
E = Eo + (RT/nF) ln ([electron acceptor]/ [electron donor] )
Standard reduction potentials and free
energy
• Relationship between standard free-energy
change and the standard reduction potential:
DGo’ = -nFDEo’
n = # electrons transferred
F = Faraday constant (96.48 kJ V-1)
DEo’ = Eo’electron acceptor - Eo’electron donor
NADH and NADPH act with dehydrogenases
as
electron carriers
H: - +soluble
H+
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From vitamin niacin (source of
the nicotinamide)
Accepts a hydride ion and
transformed into the reduced
form.
NADH absorb at 340 nm.
NAD generally functions in
oxidations--- part of a catabolic
reaction, NADPH is the usual
coenzyme in reduction– part of
anabolic reaction
Rossmann fold: most
dehydrogenase that use NAD
or NADP bind the cofactor in
the conserved protein domain
Three Ds:
Dermatitis
Diarrhea
Dementia
death
Structure of oxidized and
reduced FAD and FMN
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Flavin Nucleotides are tightly
bound in flavoproteins. Accepts 1
or 2 electrons
Oxidized flavoproteins have an
absorption maximum near 570 nm;
reduced forms shifts to about 450
nm.
Do not transfer electron by
diffusing from one enzyme to
another. Provide a means by
which the flavoprotein can
temporarily hold electron wile it
catalyzes electron transfer from a
reduce substrate to an electron
acceptor.
Variability in the standard
reduction potential of the bound
flavin nucleotide.
Complex -may bound Fe or Mo
Catabolism produces compounds
for energy utilization
• Three types of compounds are produced that
mediate the release of energy
(1) Acetyl CoA
(2) Nucleoside triphosphates (e.g. ATP)
(3) Reduced coenzymes (NADH, FADH2, QH2)
Compartmentation
and
Interorgan Metabolism
• Compartmentation of metabolic processes permits:
- separate pools of metabolites within a cell
- simultaneous operation of opposing metabolic
paths
- high local concentrations of metabolites
- coordinated regulation of enzymes
• Example: fatty acid synthesis enzymes (cytosol),
fatty acid breakdown enzymes (mitochondria)
Compartmentation of
metabolic processes