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Bioenergetics and Metabolism
Lecture 24
Key Concepts
• Energy Conversion in Biological Systems
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Review of thermodynamic principles
Sunlight is the ultimate source of energy on planet Earth
Energy conversion by coupled oxidation and reduction reactions
The adenylate system is used for short term energy storage
• Overview of Metabolic Pathways
– Metabolic pathways consist of linked enzymatic reactions
– The six major groups of primary metabolic pathways in nature
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Energy Conversion in Biological Systems
Concentration of biomolecules and ions inside of a
cell must be very different than that of the
environment
Gradients
Compartmentalization
An organism at equilibrium with the
environment is no longer alive
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Energy conversion in biological systems is
used to perform work
• chemical work in the form of macromolecular
biosynthesis of organic molecules
• osmotic work to maintain a concentration of
intracellular salts and organic molecules that is
different than the extracellular milieu
• mechanical work in the form of flagellar rotation
or muscle contraction
Cycling of resources and “waste” between
environment and a living cell provides
materials for energy conversion
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Thermodynamic principles govern energy
conversion in metabolic processes
1. First Law of Thermodynamics
2. Second Law of Thermodynamics
3. Gibbs Free Energy
First Law of Thermodynamics
• Energy cannot be created or destroyed – it can
only be converted between forms
Antoine Laurent Lavoisier
and the guinea pig, 1783
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Using a "bomb" calorimeter to measure heat
transfer as a result of combustion in pure oxygen
Example: glucose
Temperature increase of the surrounding water is
a measurement of the amount of energy stored in
the glucose
C6H12O6 + 6 O2 → 6 CO2 + 6 H2O + heat
Where heat = q = ∆E = 3.75 ºC/kilogram of water
Calorie
• Calorie (kcal) was originally defined by the
amount of heat energy required to raise 1
kilogram of water from 14.5 ºC to 15.5 ºC.
• This can also be expressed in the international
unit of measurement the Joule (J) in which 1
Calorie = 1 kcal = 4.184 kJ
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Total energy
potential of 1
gram of glucose
is the same
regardless of the
metabolic path
taken
Second Law of Thermodynamics
• All natural processes in the Universe tend
towards disorder
• Entropy (S)
• Energy is required to restrain the natural
tendency toward disorder
• An increase in entropy is the natural process
that happens when a cell dies.
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Think cool thoughts
Gibbs Free Energy
∆G° (“delta G naught”)
Change in free energy (∆G) under standard
conditions
(what are these again?)
spontaneity of a reaction A ↔ B
∆G° = - RT • ln(Keq) (remember lecture 2?)
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Concepts to review
∆Gº = 0
∆Gº < 0
∆Gº > 0
Equilibrium
Exergonic
Endergonic
∆G°’
∆G°’ is important in Metabolism
• Use of shared intermediates
• The free energy released from ATP
hydrolysis is used drive unfavorable reactions
• The actual change in free energy (∆G) of a
reaction can be determined
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Use of shared intermediates
Product of reaction 1 is the substrate for reaction 2
The ∆Gº’ of a coupled reaction is the sum of the
∆Gº’ values for each individual reaction
A↔B
B↔C
A↔C
∆Gº’ = +4 kJ/mol
∆Gº’ = -10 kJ/mol
∆Gº’ = -6 kJ/mol
Free energy released from ATP hydrolysis is
used drive unfavorable reactions
ATP hydrolysis: ∆Gº’ = - 30.5 kJ/mol
The first step in glycolysis is catalyzed by the enzyme
hexokinase and utilizes ATP hydrolysis to drive the
unfavorable reaction of glucose phosphorylation in a
coupled reaction
Glucose + Pi ↔ glucose 6-phosphate + H2O
ATP + H2O ↔ ADP + Pi
Glucose + ATP ↔ glucose 6-phosphate + ADP
∆Gº’ = +13.8 kJ/mol
∆Gº’ = -30.5 kJ/mol
∆Gº’ = -16.7 kJ/mol
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The actual change in free energy (∆G) of the
reaction A ↔ B is the sum of the change in
standard free energy ∆G°’ and the term:
RT • ln[B]actual/[A]actual
∆G = ∆Gº’+ RT • ln [B]actual / [A]actual
mass action ratio = [B]actual/[A]actual
This is NOT Keq:
Keq = [B]equilibrium/[A]equilibrium
If the system is a equilibrium, it is DEAD!
Sunlight is the ultimate source of energy
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Energy conversion by coupled oxidation and
reduction reactions
• redox reactions
– involve the transfer of electrons from one compound
to another
– the oxidation of one compound results in the
reduction of another
Metabolic redox reactions
• Catalyzed by enzymes called dehydrogenases
and oxidases
• Involve coenzymes such as nicotinamide
adenine dinucleotide (NADH and NAD+) and
flavin adenine dinucleotide (FADH2 and FAD)
that serve as electron donors and acceptors
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Example: Oxidation of Glucose leads to
reduced forms of cofactors NADH or FADH2
The adenylate system is used for short term
energy storage
• ATP synthesis reaction captures redox energy in
the form of phosphoanhydride bond energy
Highest Energy!
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Catabolic processes produce ATP
Anabolic processes require ATP
Catabolic processes:
break down molecules
Anabolic processes:
build molecules
The Adenylate System
• Interconversion of low and high energy forms of
adenylate
• ATP, ADP, and AMP
• a 70 kg person requires ~100 moles of ATP
every day
• molecular weight of ATP is 507 g/mol, which
means we hydrolyze as much as 50 kg of ATP
every day
• How do we do it?
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Recycle adenylate forms by reforming ATP
from ADP + Pi
(adenylate kinase)
AMP + ATP ↔ 2 ADP
(phosphorylating systems)
oxidative phosphorylation and photophosphorylation
2 ADP + 2 Pi ↔ ATP + ATP
Net AMP + 2 Pi ↔ ATP
Energy Charge (EC)
ATP is the high energy form of the adenylate system
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Normal Range of EC for Cells
[ATP] is higher than [ADP] or [AMP]
Overview of Metabolism
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A metabolic pathway is a set of linked reactions
• metabolism of shared intermediates
• first reaction step and regulation often linked
Positive vs. Negative regulation
Feedback inhibition
Different types of metabolic pathways
Substrate concentration and
enzyme activity levels affect flux
through metabolic pathways
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Example: Glucose metabolism in the liver
before and after breakfast
Glucagon signaling in liver cells
activates both a catabolic
pathway (glycogen degradation)
and an anabolic pathway
(gluconeogenesis), while at the
same time inhibiting the
catabolism of glucose by the
glycolytic pathway.
Example: Glucose metabolism in the liver
before and after breakfast
Within an hour of eating a bowl of
cereal and drinking a cup of fruit
juice, your insulin levels increase
due to elevated blood glucose
causing activation of the insulin
signaling pathway and
stimulation of glucose uptake,
glycogen synthesis, and an
increase in glucose catabolism
by the glycolytic pathway.
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6 major groups of metabolic pathways in
nature
• Metabolic pathways are highly interdependent
and exquisitely controlled by substrate
availability and enzyme activity levels
• Key to understanding metabolic integration in
terms of nutrition, exercise, and disease (e.g.,
diabetes and obesity) is learning how metabolic
flux between pathways is regulated and
controlled
http://www.expasy.org/cgi-bin/show_thumbnails.pl
Should you memorize this chart?
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Interdependence of
six major groups of
pathways
Hierarchical Nature of Metabolism
Four classes of macromolecules
(proteins, nucleic acids,
carbohydrates, and lipids)
Six primary metabolite groups
(amino acids, nucleotides, fatty
acids, glucose, pyruvate, acetyl CoA)
Six small biomolecules (NH4+, CO2,
NADH, O2, ATP, H2O)
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We will start off the discussion of each
new pathway by answering the following
four questions about the pathway:
1. What does the pathway accomplish for the cell?
2. What is the overall net reaction of the pathway?
3. What are the key regulated enzymes in the pathway?
4. What are examples of this pathway in real life?
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