Key Concepts

• Energy is captured and stored into reduced bonds (C=O

C-C and C-H)
• This is ultimately transferred to ATP following their
oxidation
• The phosphate bond of ATP is an ancient energy store,
that now acts as a short term energy source for
biological work
• Thermodynamic laws govern life!
• The free energy (ΔGo') released on ATP hydrolysis is
used for biological work (e.g. muscle contraction, ion
transfer)
• ΔGo‘ can be calculated from thermodynamic laws
• The more negative the ΔGo‘ the greater the likelihood a
reaction occurs
• The hydrolysis of ATP to ADP and inorganic phosphate
releases most of the ΔG in ATP
Energy flow

Anabolic
process

Catabolic
process
What is a common theme here?
3
Different food sources
release different amounts
of energy when
combusted (kJ/g)

least
• Carbohydrate
• Protein
• Alcohol
• Fat
most
4
Caloric content of dietary
components
The energy within food
(energy/gram)
Food kcal/g kJ/g
Carbohydrate 4 16.7
Protein 4 16.7
Alcohol 7 Add own
29.3
table
Fat 9 37.7

From: Basic Medical Biology, Williams and Wilkins

But combustion differs from metabolism

• Carbohydrate most

• Protein
• Fat
• Alcohol
least

?
Fuel consumption of the average 70 kg
male after an overnight fast (in
kilograms and as a percentage of total
calories)

From: Basic Medical Biology, Williams and Wilkins

Why is combustion different to
metabolism, and then why use fat?

• Enzymes work on C-H and -O-H bonds

• Molecules must be rearranged
• Fat has slightly less energy per bond, but
stores well
• Also fat can not be metabolised without O2

8
Overview of fuels and
energy extraction

Macronutrient fuel sources

that supply substrates for
regenerating ATP

From: Exercise Physiology 5th edition.

McArdle, Katch and Katch
Three Stages of Catabolism
Acetyl-CoA is a hub molecule

1) Hydrolysis of complex
molecules to their
building blocks

2) Conversion of building
blocks to Acetyl CoA
3) Oxidation of acetyl CoA
– occurs by oxidative
phosphorylation

We will come back to this

11
The ATP – ADP cycle

ATP + H2O
CO2

O2
Energy from catabolism
(exergonic, energy-releasing
processes)
Energy for cellular work
ADP + P i (endergonic, energy-consuming
processes)
 Membrane protein

P P
i

Solute Solute transported

(a) Transport work: ATP phosphorylates
transport proteins ADP
ATP +
Pi
Vesicle Cytoskeletal track

ATP

Protein moved
Motor protein
(b) Mechanical work: ATP binds non-covalently
to motor proteins, then is hydrolyzed
This figure illustrates (a) the structure of ATP and (b) the hydrolysis of ATP to
yield ADP and inorganic phosphate. In the cell, most hydroxyl groups of
phosphates are ionised (-O-).
ATP?
• ATP is not really “universal”, cells use GTP, UTP and also
creatine phosphate (CrP*).
• But ATP is the most abundant, frequently used and likely
ancestral.
• Phosphoanhydride bond of ATP relatively stable in water at
physiological pH
• Overall release of energy on hydrolysis is exothermic
reaction (outwards flow of energy).
• Other bonds can yield more energy, but less water stable!
• While ATP can be hydrolyzed twice to ADP and AMP, most of
the “power” is in the 3rd P!
* CrP We will discuss this later
How does ATP work?
Resonance
Or charge delocalisation

Phosphate
-
- - -

17
 ATP is special!

• The energy released from the terminal

phosphate (Pi) of anhydride bond
hydrolysis, is high.

• The free energy of formation (∆fG0) of

ATP is greater than the sum of the
“products of formation” of ADP + Pi !!
What is ∆G0?
• Laws of thermodynamics and life
• 1) Energy can not be created or
destroyed, it changes form
• 2) The Universe is becoming
increasingly disordered

ΔH- TΔS= ΔG
1st law
heat work

ΔH = q + w
The change in ENTHALPY = heat + work done

ΔH- TΔS= ΔG
What is it?
2nd Law of Thermodynamics
The Universe tends towards disorder (increased entropy)
The symbol for
ENTROPY is S

Entropy means turning in

It is a measure of disorder

ΔH- TΔS= ΔG
•ΔH- TΔS= ΔG
ΔG = Gibbs free energy!

• This predicts whether a reaction occurs

spontaneously
• It predicts the maximum possible change in
concentrations between reactants and products
• So how much you need for a reaction, and
could make
• The more negative (- ΔG) the more work can
be done!!!!!!
• But note it does not predict the rate at which
reactions will occur!!! Important for exam
The relationship of free energy to
stability, spontaneous change,
equilibrium and work
 ∆G < 0 ∆G = 0

Short life (anaerobic

metabolism works like
this in us)

(a) An isolated hydroelectric system

(b) An open hydroelectric

system ∆G < 0
life Using a free energy
gradient to power
metabolism

∆G < 0
∆G < 0
∆G < 0 A more
productive life
Although
somewhat
more
complicated

(c) A multistep open hydroelectric system

How does Δ Go’ relate to
ATP?
Phosphoester bond Phosphoanhydride
bonds

ATP  AMP + PPi Δ Go’ -32.2 kJ.mol-1

ATP  ADP + Pi Δ Go ’ kJ.mol-1 -30.5

so, only about 2 kJ.mol-1 comes from the 2nd P!
most of the power is in the third P!
Biochemistry 4th Edition Voet and Voet 2011 Wiley
 ATP ADP + Pi
Note that the arrows indicate that this process is
theoretically reversible, but it goes more easily to the
right, i.e. towards ATP…..
Also

In heart muscle cells ~ATP = 8-10 mM,

ADP ~0.050-0.150 mM,  200 x more ATP
(some tissues the ratio is 1000/1 ATP/ADP)
 Reactants

G Amount of
energy
released
Free energy

(∆G < 0)
Energy
Products

Progress of the reaction

(a) Exergonic reaction: energy released

Products
G

Product inhibition
Amount of
energy
required
Free energy

(∆G > 0)
Energy
Reactants

Progress of the reaction

(b) Endergonic reaction: energy required

 NH2

NH3
+ ∆G = +3.4 kcal/mol
Glu Glu
Glutamic Ammonia Glutamine
acid
(a) Endergonic reaction

1 ATP phosphorylates P
glutamic acid, + ATP + ADP
Glu Glu
making the amino
acid less stable.
NH2

P
2 Ammonia displaces NH3
the phosphate group, + + Pi
Glu Glu
forming glutamine.

(b) Coupled with ATP hydrolysis, an exergonic reaction

(c) Overall free-energy change

Lecture Exercises:

1) How does the 2nd law of thermodynamics help to explain

how a membrane may partition charged ions (i.e. H+ or Na+) to
generate a membrane potential?

Have we increased or decreased the entropy? 32

2) Cellular respiration uses glucose and oxygen, which both
have high -ΔGo', and releases CO2 and H2O, which have lower
(less negative) ΔGo'.

Is respiration spontaneous? (tip spontaneous means

energetically favourable)

Is respiration exergonic or endergonic?

What happens to the energy released from the glucose?

33
3) Myosin, or a similar motor protein, was one of Evolution’s
greatest inventions because it permitted movement such as
contraction.

Describe how hydrolysis of ATP by myosin could contribute to

the different components of the following equation.

ΔH - TΔS= ΔG

34