Chapter 13
Homework Assignment
• I have decided to alter the homework assignment
for Chapter 13.
• These problems will NOT collected but if I were to
want some practice, I would look at these
problems:
2, 4, 6, 8, 9, 10, 14, 18, 19, 22
Chapter 13
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Chapter 13
Bioenergetics
1
Bioenergetics & Metabolism
• Metabolism is a highly coordinated cellular activity in
which many multienzyme systems (pathways) cooperate
to:
– Obtain chemical energy by capturing solar energy or degrading
energy-rich nutrients
– Convert nutrients into raw materials for the production of
macromolecules
– Polymerize monomeric precursors into macromolecules
– Synthesize and degrade biomolecules required for specialized
cellular functions
• Metabolism includes hundreds of varied pathways, but
we will be focusing on the central metabolic pathways
that are common to all forms of life
Chapter 13
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Bioenergetics & Metabolism
• In a metabolic pathway, each step brings
about a small chemical change, usually the
removal, transfer or addition of an atom or
functional group.
– These intermediates are metabolites
• Catabolism is the degradative phase in
which nutrients are converted into smaller
end products
– These pathways release energy as either
ATP or reduced electron carriers (NADH,
FADH2, NADPH)
• Anabolism is the biosynthetic phase where
small precursors are built into
macromolecules
– These pathways require energy, usually in
the form of ATP or the reduced electron
carriers
Chapter 13
Fig 3, page 483
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Bioenergetics & Metabolism
Categories of Pathway
Chapter 13
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Bioenergetics & Metabolism
Complexity is Vast,
but Fundamental Principles are Not
• Four simple types of weak interactions
• Five basic classes of chemical reactions
• Five common high-energy intermediates
• A few basic types of enzyme mechanism
• A few basic classes of reaction kinetics
• A few basic principles of thermodynamics
• Energy coupling drives unfavorable reactions
Chapter 13
Bioenergetics
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3
Bioenergetics & Thermodynamics
Primer of Thermodynamic Terms
∆G = [Energy]products – [Energy]reactants
Negative if reaction is spontaneous and energy is
released (exergonic)
∆H = [Heat content]products – [Heat content]reactants
Negative if heat is released (exothermic)
∆S = [Entropy]products – [Entropy]reactants
Positive if products are “simpler” (i.e. more disordered)
Chapter 13
Overall: ∆G = ∆H - T∆S
7
Bioenergetics & Thermodynamics
Recall from previously:
Free Energy Nomenclature
∆Go: used by the chemist for reactions under
“standard conditions” of pressure, temperature,
and solutes at 1M…
VERSUS
∆G’o: used by the biochemist for reactions
under “standard conditions” of pressure,
temperature, and pH 7 (because we can’t work
at 1M H+!)
Chapter 13
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4
Bioenergetics & Thermodynamics
Recall the 2nd REALLY IMPORTANT Equation
• There is a direct relationship between net free
energy change and the equilibrium constant
• Which is fixed for any given reaction, because
∆G’o refers to standard conditions (1 M conc’s,
pH 7, 25°C, 1 atmosphere pressure, etc.)
Reactants ⇄ Products
∆G'o = − RT ln
[Products]
= − RT ln K' eq
[Reactants ]
Chapter 13
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Bioenergetics & Thermodynamics
Free Energy and Equilibrium Constant are Alternative
Expressions for the Same Thing
• If the K’eq value is high,
what is favored?
• What would you expect the
corresponding ∆G’° to be?
• If the ∆G’° value is high,
what is favored?
• What would you expect the
corresponding K’eq to be?
Chapter 13
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Bioenergetics & Thermodynamics
But what if conditions aren’t standard?
• Then you have to modify the equation by
including the prevailing conditions at the actual
start of the reaction
K’Start
[P]
o
∆G Actual = ∆G' + RT ln
[S]
• Common sense should help you
• If at equilibrium, products predominate (- ∆G’°),
but at start you have even more products (large
K’Start), then the reaction will go backwards
because ∆GActual will be positive!
• A thermodynamic feedback inhibition!
Chapter 13
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Bioenergetics & Thermodynamics
∆G’s are Additive
• In the case of sequential reactions, each
reaction has its own K’eq and ∆G’°
• The ∆G’° values for the two reactions are
additive, yielding a ∆G’°total for the summed
reactions.
Chapter 13
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Bioenergetics & Thermodynamics
K’eq are Multiplicative
• Keq’s are multiplicative, and will yield the
equilibrium constant for the overall reaction
(starting from standard conditions)
• Here, too, Kstart can be compared to the
overall Keq, to see whether a particular set of
reaction conditions will proceed or not
K’eq (1)
K’eq (2)
Product
K’eq (1) x K’eq (2)
Chapter 13
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Bioenergetics & Thermodynamics
What Keeps a Reaction Going?
• The ∆G tells whether a reaction will go, from a
particular set of prevailing conditions
• But as products build up (and equilibrium is
approached), ∆G will approach zero
• The reaction will continue, only if one or more products
are removed:
– By another reaction with a high negative ∆G
– By moving them to another cellular compartment
– By secreting/excreting them out of the cell
– By converting them to another form (e.g. solute to gas)
Chapter 13
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Bioenergetics & Thermodynamics
High-energy Compounds Like ATP have Large, -∆G’s
• The hydrolysis of the terminal
phosphoanhydride bond in ATP
separates one of the three negatively
charged groups
What would this relieve?
• The energy released and the phosphate
group can be used in group transfers to
drive coupled endergonic reactions
• Under cellular conditions much more
energy may be available than the
standard ∆G’o would suggest
Chapter 13
• So, why doesn’t this reaction just
happen all of the time?
15
Bioenergetics & Thermodynamics
Thioesters Have Even More
What’s a thioester?
Chapter 13
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8
Bioenergetics & Thermodynamics
But the BIG Winner is….
Why do we get so much energy?
Chapter 13
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Bioenergetics & Thermodynamics
So, the Obvious Questions is….
• Why Do Phosphorylated Compounds & Thioesters
Have Large Free Energies of Hydrolysis?
• Because products are much more stable than
reactants, due to:
– Relief of bond strain that was due to electrostatic repulsion in
reactants
– Products are stabilized by ionization
– Products are stabilized by isomerization
– Products are stabilized by resonance
Find at least one example for each of
these and understand Figures 13-1 to 13-6
Chapter 13
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Bioenergetics & Thermodynamics
The Big Five: Four + One
Acetyl-(S)CoA
Considered high energy
if ∆G’° < - 25 kJ/mol
Chapter 13
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Bioenergetics & Thermodynamics
ATP is the Universal Energy Currency of Cells
• High energy phosphoryl compounds are
formed during catabolism
• As a means of activating other compounds
for further chemical transformations
• ATP is energetically rich, kinetically stable
– Intermediate group-transfer potential
– Great versatility in what groups it can transfer
• It converts lower energy compounds into
more reactive species
Chapter 13
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10
Bioenergetics & Thermodynamics
“Hydrolysis” of ATP is Really a Group Transfer
• It is commonly but mistakenly
said that “ATP hydrolysis”
drives a chemical reaction (a)
• In fact, a moiety of ATP is
usually transferred covalently
to enzyme or substrate,
transiently raising its free
energy content (b)
Chapter 13
21
Bioenergetics & Thermodynamics
What Moieties of ATP Can Be Transferred?
• Reactions of ATP are
generally SN2
nucleophilic
displacements
• Any of the 3 phosphorus
atoms may be the
electrophilic target for
nucleophilic attack by:
(1) An alcohol
(2) A carboxyl group
(3) A phosphoanyhdride
Chapter 13
- 19 kJ/mol
- 30.5 kJ/mol - 45.6 kJ/mol
The bridge oxygen comes
from the nucleophile
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11
Biological Redox Reactions
Metabolic Pathways and Energy
• Energy-containing nutrients are typically
in low oxidation states (Reduced forms).
Example: fats.
• Energy-depleted end products are
typically in high oxidation states (oxidized
forms). Example: CO2.
• NADH, FADH2 are strong reducing
agents used in converting low-energy
precursors to cell macromolecules.
• Redox chemistry is important in
metabolism.
Chapter 13
23
Biological Redox Reactions
Nutrients and energy
• The carbon oxidation energy in nutrients can be used to create a
compound with high phosphoryl transfer potential
• This energy also can be used to create an ion gradient
• Either of these result in the end in the formation of ATP.
Chapter 13
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12
Biological Redox Reactions
Nutrients are fuels we "burn"
• The carbon oxidation energy can be used to create a compound
with high phosphoryl transfer potential
• This energy is harnessed through reactions converting glucose to
oxidized forms.
• Note the role of oxygen …
Berg Fig. 16.11
Chapter 13
25
Biological Redox Reactions
ATP synthesis is driven by energy from nutrients
• The terminal electron acceptor is oxygen, which has a high
reduction potential (high affinity for protons).
• Thus energy is released when electrons are dumped into oxygen
(making water)
• This energy is used to pump protons from the mitochondrial matrix
into the intermembrane space
• Thus establishing a
pH gradient across
the membrane
which is used to
drive ATP synthesis
Chapter 13
Berg 18-2
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13
Biological Redox Reactions
Who Owns Carbon’s Electrons?
More Reduced
More Oxidized
Chapter 13
27
Biological Redox Reactions
How does this correspond to energy?
• The ultimate electron acceptor is O2.
Berg Fig. 14.9
• Thus the more reduced a carbon is to begin with, the more energy
that can be released upon oxidation.
• Recall the fuel molecules…
Chapter 13
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14
Biological Redox Reactions
Who Catalyzes these Reactions?
• A carbon atom can lose electrons (undergo oxidation),
even in the absence of oxygen
Alkane
Dehydrogenase
Alkene + H2
• In this case, the oxidation is coincident with the loss of
hydrogen
• The oxidation reaction is synonymous with a
dehydrogenation reaction
• The enzymes that catalyze these reactions are
dehydrogenases!
Chapter 13
29
Biological Redox Reactions
When Electrons are Transferred from One
Molecule to Another, How Do They Go?
• Directly as electrons:
Fe2+ + Cu2+ ⇄ Fe3+ + Cu+
• As hydrogen atoms:
AH2 ⇄ A + 2 e- + 2 H+
• As a hydride ion (:H-)
• By directly combining with oxygen:
R-CH3 + ½ O2 ⇄ R-CH2-OH
• All four types occur in cells
• The term Reducing Equivalent is used to designate a single
electron equivalent participating in a redox reaction, regardless
of its type
Chapter 13
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15
Biological Redox Reactions
LEO the lion goes GER
Lose Zn(s) → Zn2+ (aq) + 2 eElectrons
If the electron(s) is on the
product side of the reaction,
Oxidation
it is an oxidation reaction!
A substance which loses
electrons (oxidized) is
called a reducing agent.
Its oxidation number
increases.
Chapter 13
31
Biological Redox Reactions
LEO the lion goes GER
Gain Cu2+ (aq) + 2 e- → Cu(s)
Electrons
If the electron(s) is on the
reactant side of the
Reduction
A substance which gains
electrons (reduced) is
called the oxidizing
agent.
Its oxidation number
decreases.
Chapter 13
reaction, it is a reduction
reaction!
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16
Biological Redox Reactions
• The transfer of electrons between or among reactants is
called the oxidation or reduction of species depending
on which way the electrons are flowing.
• Oxidation and reduction must occur together. They
cannot exist alone.
• Therefore, a redox reaction can be broken into two halfreactions, one a reduction and the other an oxidation
Chapter 13
33
Biological Redox Reactions
What About the Energy of Moving Electrons Around?
• Measure the current to or
from a standard reference
redox pair, the hydrogen
electrode
e-
H+
---H2
Chapter 13
NAD+
--------NADH
E’o = - 0.32 V
• The half-cell with the
stronger tendency to
acquire electrons is
assigned a positive value
of E’o, and has a higher
reduction potential
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17
Who Likes
Electrons More?
Good Oxidizing
Agents
Propensity to gain electrons
Propensity to shed electrons
Good Reducing
Agents
Chapter 13
35
Biological Redox Reactions
Standard Reduction Potentials
• The standard cell potential of any galvanic cell is the sum of
the standard half-reaction potentials for the oxidation and
reduction half-cells.
∆E’° = E’°oxidation + E’°reduction
• Standard half-cell potentials are always quoted as a
reduction process (See Table 18.1).
• If your half-reaction is an oxidation, the numerical value is
the same as in the Table but the sign must be changed.
Chapter 13
E’°reduction = - E’°oxidation
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Biological Redox Reactions
Spontaneity of a Reaction
• The value of E˚cell is also related to the
thermodynamic quantity of ∆G˚.
∆G’˚ = –nF∆E’˚
n = # of moles of e- transferred
F = the Faraday constant (96,485 C/mol e-)
• For spontaneous reactions, ∆G’˚ is
negative and ∆E’° is positive
Chapter 13
37
Biological Redox Reactions
Calculating ∆E’° and ∆G’°
Acetaldehyde + NADH + H+ → Ethanol + NAD+
Acetaldehyde + 2H+ + 2e- → Ethanol
E’°red = - 0.197 V
NADH → NAD+ + H+ + 2e-
E’°oxd = + 0.320 V
∆G’˚ = –nF∆E’˚
∆E’° = 0.123 V
∆G’˚ = – (2)(96485 C/mol)(0.123 V)
∆G’˚ = – 2.37 x 104 C V / mol = - 23.7 kJ/mol
Chapter 13
This is under standard conditions!
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19
Biological Redox Reactions
If you know the standard reduction potentials, E’o
• And you know the concentrations of the species participating
in the reaction
• You can calculate the free energy change for the oxidationreduction reaction under non-standard conditions because:
E = E’o + (RT/nF) ln [electron acceptor]
[electron donor]
and
Thus the free energy is
∆G = - nF∆E favorable, if ∆E is positive!
Chapter 13
See examples in the text…
39
Biological Redox Reactions
Standard values for various chemical reactions
Know
these
two
Chapter 13
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20
Biological Redox Reactions
The Actual Energetics of Glycolysis
• Based on actual concentrations of reactants and products.
• Note that 7 are near equilibrium - only 3 of the steps are
energetically “irreversible”.
• How then can glucose be synthesized?
Chapter 13
41
Biological Redox Reactions
The Free Energy Release from the
Oxidation of Glucose is Gradual
• The total free energy change from glucose to
carbon dioxide and water is – 2840 kJ/mol, but
individual oxidation steps generate ~ 60 kJ/mol,
• This amount is just enough to make an ATP
molecule
• The electrons that are removed in these steps are
transferred to coenzymes that are specialized for
carrying electrons, such as:
NAD+ and FAD
Chapter 13
42
21
Biological Redox Reactions
How NAD+ (or NADP+) Carries Electrons
x
These Nicotinamide Adenine
Dinucleotide derivatives are
reduced by the stereospecific addition of a hydride
ion (2 electrons and a proton)
• As coenzymes, they are only loosely associated with their
proteins, serving as water-soluble electron carriers
Chapter 13
43
Biological Redox Reactions
How Riboflavin Derivatives Carry Electrons
• These flavin derivatives are reduced
by the sequential addition of 2
hydrogen atoms (2 electrons and 2
protons)
• As coenzymes, they are bound
tightly in a flavoprotein complex
Chapter 13
44
22
Biological Redox Reactions
The Importance of Three Vitamins
• Niacin (vitamin B3)
– Synthesized from tryptophan
– The electron-carrying moiety of NAD
and NADP
– Deficiency affects all the NAD(P)dependent dehydrogenases
– Resulting in the human disease
pellagra, causing dermatitis, diarrhea,
dementia and often death
– Alcohol reduces intestinal absorption of
niacin, and alcoholics often display
symptoms of pellagra
Chapter 13
45
Biological Redox Reactions
The Importance of Three Vitamins
• Riboflavin (Vitamin B2)
– Precursor to the flavin nucleotide
coenzymes
– The electron-carrying moiety of FAD and
FMN
– Deficiency affects function of
flavoproteins, to which these coenzymes
are tightly bound
– Resulting in cheilosis (inflammation of
corners of the mouth), glossitis (magenta
tongue), and seborrheic (“greasy”)
dermatitis
– “Ariboflavinosis” usually accompanies a
lack of other water-soluble vitamins
Chapter 13
46
23
Biological Redox Reactions
The Importance of Three Vitamins
• Thiamine (Vitamin B1)
– Essential for the coenzyme TPP
– Whose thiazolium ring can produce a carbanion active in
decarboxylation reactions, or in rearrangements involving
activated acetaldehyde groups
– Deficiency leads to a condition called “beriberi”
– Characterized by distal edema (tissue swelling), pain, paralysis,
and eventually death
Chapter 13
47
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