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Energy use in biology has to obey laws of physics!

BIOL1020/BIOL7020 Thermodynamics is a branch of physics that deals with energy and the work it can do. It has
Prof Kate Stacey important laws that cover what is possible in chemical reactions and biological systems.
School of Chemistry and Molecular Biosciences
The first law of thermodynamics:
Energy can be transferred and transformed, but it cannot be created or destroyed

Week 3: Cellular energy The second law of thermodynamics:

The state of entropy (disorder) of the universe, will always increase over time.

Note that the online material used a definition of of the second law of thermodynamics from the glossary of you textbook,
Please Note: The material in this lecture overlaps with the online information. It is being presented here a bit
and it is confusing, as it makes it sound like entropy has to increase in every reaction. This is not the case, and hence I want
differently to try and reinforce information. But, the information on glycolysis, the citric acid (Krebs) cycle, and
to go over this here.
the electron transport chain is very much the same on these slides as what is in the online lecture. So I am not
going to go through that in any detail in this lecture, but since you get no “handouts” from the online lectures, the
slides are all included here so that you have a copy of the images that are used in the online presentations. You
can use these slides to annotate when you are watching the online presentation.

Readings: Campbell’s Biology 12th Ed: Ch8 (8.1-8.4), Ch9 (9.1-9.4), Ch10 (10.0-10.1)

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What is entropy? Some examples of how entropy can increase:

• Entropy can be interpreted as randomness or lack of order. Things naturally tend to become disordered. Think • Ice melting
of the decay of buildings that are not looked after. It takes energy input to maintain order. • A liquid turning into a gas
• Even though the total entropy of the universe is always increasing, we can decrease entropy in local systems, • A reaction breaking down a macromolecule into smaller molecules, e.g. starch to glucose
by putting in energy. Otherwise, complex molecules and living systems could not exist.
• Wood burning i.e. cellulose to generate CO 2 and H 2O and heat
• Nevertheless, entropy is a consideration in every chemical reaction. Increasing entropy makes reactions more
likely to be energetically favourable.

Some examples of entropy decreasing:

• Protein synthesis from amino acids
• Photosynthesis to make sugars from CO 2
• Synthesis of DNA from thousands of nucleotides
• Compressing a gas

Note that to decrease entropy, there needs to be an energy input.

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The total energy of reactions is defined by “Gibbs free energy” In living organisms energy conversions are linked to chemical
reactions called metabolism
• Gibbs free energy is the amount of energy in a system that can be used to do work while
pressure and temperature are constant

• For a chemical reaction, the most important parameter is the CHANGE in the Gibbs free • Metabolic reactions can
energy (DG) that occurs during the reaction. – Break down molecules/ release energy (catabolic reactions,
DG = Gfinal state – Ginitial state
negative DG ) or
• Free energy depends on both entropy and enthalpy
– Synthesize molecules/ consume energy (anabolic reactions,
• Enthalpy is the stored energy that can be released as heat.
overall positive DG)
• Reactions are definitely energetically favourable (i.e. DG < 0) if:
– Entropy increases, and
– Enthalpy decreases – i.e. heat is released as products have lower enthalpy than reactants.
Metabolism = catabolic + anabolic reactions

• If both of these conditions are not met, reactions can still happen, but they may need an
energy input.

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Exergonic reactions have a negative change in Gibbs free energy Endergonic reactions have a positive change in Gibbs free energy

Energy level
of the
reactants i.e.
nucleotides Although the reaction already
requires energy input to
proceed there is still an
activation energy barrier!

DG – the DG = G final state – G initial state

change in
free energy
DG = G final state – G initial state

Most reactions that synthesise cellular materials (e.g. DNA, lipids, proteins, amino
Energy level of the products acids) are endergonic reactions.
Figures 8.6 (polynucleotides/ new DNA) Figure 8.6

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Properties of the two basic types of cellular metabolic reactions If complex molecules store lots of
energy, how can they be stable. Why
Exergonic reactions Endergonic reactions aren’t spontaneous reactions all
instantaneous??
• Negative DG • Positive DG
• Releases energy during reaction • Require energy input Why don’t we spontaneously
• Reactant energy level: HIGH • Reactant energy level: LOW combust???
• Product energy level: LOW • Product energy level: HIGH
(And no, we don’t, if you were wondering)
• Used in catabolism/ energy generation • Typical for anabolism/ macromolecule
• “Spontaneous” = energetically synthesis
favourable • Non-spontaneous
• Have activation energy barrier • Have activation energy barrier

Note that when chemists refer to a reaction as spontaneous, they just mean that the reaction will
release energy, not that it going to happen really rapidly……

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Activation energy (EA) Enzymes lower the activation energy to catalyse reactions
Spontaneous reactions still have an Enzymes are proteins
activation energy “hump” (E A ) that
needs to be got over, for the reaction to Enzymes catalyse (speed up)
happen. reactions by reducing the
activation energy needed.
Heat is a common means of supplying They do not affect the DG.
energy to overcome E A and enable the
reactants to enter a higher energy They have an active site,
transition state, that destabilises their usually a pocket, where the
bonds. reactants (‘substrates’) bind

The burning of wood is obviously Amino acids in the enzyme

exergonic, but does not start until active site bind the
friction or a a heat source is applied to substrate/s and help to
get over the E A
destablise particular bonds in
The E A will determine the rate of the order to promote the reaction.
reaction.

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Enzyme Action Cells require a lot of ‘endergonic’ reactions to grow

Enzymes can go through many rounds of – where does the energy come from?
catalysis

This shows two substrate molecules

reacting together yielding two different • A particular endergonic reaction is coupled with an exergonic reaction that
products. provides the energy.
Enzymes may also cleave one substrate
molecules into two, join two molecules • A reaction where this occurs is called a ‘coupled reaction’
together, or just modify one substrate.

Enzymes are very specific for particular • The exergonic half of the coupled reactions usually involve hydrolysis of ATP or
reactions. related compounds.
A single enzyme might catalyse 1000
reactions per second.

Most enzyme names end in “ase”:

Protease, amylase, DNase etc

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Energy is released from ATP by hydrolysis of bonds between phosphate groups Example of a coupled reaction: Synthesis of glutamine from glutamic acid
Basic reaction properties:

Glutamic acid can be ‘energetically activated’ by reacting with ATP

ATP + H2O → ADP + Pi

ΔG = -7.3 kcal/mol: ~ -30.8 kJ/mol

• Phosphoanhydride bonds are unstable because of electrostatic repulsion between the oxygen
atoms on the phospho-groups.
• ADP has less electrostatic repulsion and therefore has a lower potential energy
• NB, ATP is also one of the 4 nucleotides used in RNA synthesis!!
Figure 8.10

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Every day cells use a huge number of ATP molecules To make ATP, the energy stored in glucose is released in small steps
Overall This is just the same overall
glucose C6H12O 6 + 6 O 2 → 6 CO 2 + 6 H 2O reaction as if you burn glucose!
Example: Separation of DNA strands by metabolism
the enzyme helicase is a form of ∆G = -686 kcal/mol (-2870 kJ/mol)
mechanical work

This is a reaction with a positive DG, and

hydrolysis of 1 ATP is required for the
separation of each base pair along the
DNA strand!

Figure 16.13
An E. coli chromosome has approx
4.639 mil base pairs… just to separate
the DNA strands during replication • Breakdown of glucose in multiple steps gives controlled release of energy that is trapped in ATP
4.639 mil ATP molecules are required!! • At each step electrons are moved between the reactants and products to enable breaking of
chemical bonds (REDOX reactions)

Figure 9.5

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What does “redox” - oxidation and reduction mean? NAD(H) –an electron carrier for the cell
• In many cases oxidation of organic molecules involves increasing oxygen atoms NAD+ NADH
(forming C-O bonds) and reduction involves increasing hydrogen atoms (increasing C-H
bonds).

• However, this is not a universal definition, and in chemistry generally it refers to the gain
or loss of electrons. e.g. iron is oxidized in going from Fe2+ to Fe3+
ribose
• Understanding this definition relates to changes of oxygen and hydrogen content in
organic molecules relies on understanding that oxygen is electronegative, and pulls
electrons away from carbon, whereas the C-H bond has a fairly even sharing of adenine
adenine

electrons. ribose

• Definition: Oxidation is loss of electrons and reduction is gain of electrons

• Useful Mnemonic: With respect to electrons: • NAD = Nicotinamide adenine dinucleotide – related to ATP structure
OILRIG • Oxidised NAD + is reduced to NADH by the gain of 2 electrons and one proton (H + )

Oxidation is loss • NADH can be used within other redox reactions within the cell
Reduction is gain • NADH is used in the last phase of cellular respiration, powering the electron transport chain

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Cellular respiration has three major stages: Cellular respiration

Produce mostly NADH Produces
& only little ATP lots of ATP Stage I: glycolysis
Stage I: glycolysis Stage II: pyruvate Stage III: • One 6-carbon glucose molecule is
oxidation & citric oxidative
phosphorylation broken down to two 3-carbon pyruvate
acid cycle
molecules.
• Produces two NADH and two ATP (net)
FACT: Cellular respiration using • Uses 10 individual enzymatic steps
these pathways uses 24 individual
enzymatic steps!

No – you don’t need to know all

the enzymatic steps J

Figure 9.6

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Cellular respiration – stage IIA pyruvate oxidation: Cellular respiration stage IIB: citric acid cycle (Krebs cycle)

Stage IIB: citric acid cycle

Stage IIA: pyruvate Oxidation
• Produces 2 CO 2 from 1 Acetyl CoA
• Pyruvate is transported into the
mitochondrion • Produces 1 FADH 2, 3 NADH and 1 ATP (via
GTP) by substrate phosphorylation per
• Produces Acetyl-CoA and carbon
acetyl-CoA
dioxide
• CoA = coenzyme A, it becomes linked to
• Uses 8 individual enzymatic steps
the acetate molecule during the reaction

• Catalyzed by an enzyme complex End result:

called pyruvate dehydrogenase Acetyl CoA is fully converted into high energy
carriers (1 FADH 2 and 3 NADH) plus one ATP
• Produces 1 NADH per pyruvate and
no ATP

Figure 9.10 Figure 9.11 + 9.12

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Cellular respiration – The respiratory or electron transport chain – a great bacterial invention J
stage III: oxidative phosphorylation Four membrane protein complexes (I-IV) that pass electrons along, in a chain

Input: NADH and FADH 2, oxygen; Output: a proton gradient and water

Mechanism: high energy electrons from NADH are passed between

• Produces 26-28 ATP per glucose molecule
complexes of increasing affinity for electrons. Energy is released and used
• Input: NADH & FADH2 to pump protons out of the mitochondrial matrix into the intermembrane
• Consists of two phases, space

• Electron transport chain (creates a proton gradient)

• Chemiosmosis (forms ATP)
Final electron acceptor:
oxygen…
this is why you need
oxygen to stay alive!

Figure 9.13
Figure 9.15
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Chemiosmosis – ATP generation by the H+ gradient The reactions of cellular respiration take place in
different cellular compartments
intermembranous space
Mechanism: There is now a gradient of H+ Glycolysis pyruvate oxidation & TCA cycle Oxidative
ions between the intermembranous space CYTOSOL MITOCHONDRIAL MATRIX phosphorylation
MITOCHONDRIAL
H+
and the mitochondrial matrix – the MEMBRANES
H+ H+
H+ H+ H+ H
+ “chemiosmotic gradient”.
H+

The membrane is impermeable to protons

(H+), so they must flow back through a
specific carrier: ATP synthase

As the protons flow back, ATP synthase uses

mitochondrial matrix the potential energy released to make 1 ATP
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for every 4 protons

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Now we know how respiration works – Chemically, photosynthesis is the

what about photosynthesis? reverse of respiration

Photosynthesis: becomes reduced

6 CO2 + 6 H 2O + energy → C6H12O 6 + 6 O 2

becomes oxidized

Respiration:
becomes oxidized

C6H12O 6 + 6 O 2 → 6 CO 2 + 6 H 2O + energy

becomes reduced
Figures 10.4, 9.2

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Respiration in mitochondria (plant & animals), photosynthesis in chloroplasts Photosynthesis and respiration share many common elements
mitochondrion chloroplast Oxidative phosphorylation Light reactions
• in plant and animal cells • only in plant and algal cells (respiration) (photosynthesis)
• Site of cellular respiration • Site of photosynthesis
• Double membrane • Double membrane and thylakoids • Consumes NADH/FADH2 • Produce NADPH
• Contains DNA • Contains DNA • Produces oxygen from water
• Reduces oxygen to water
• Bacterial origin • Bacterial origin
• Creates a proton gradient • Creates a proton gradient
• Also involved in breakdown of food • Contain chlorophyll
molecules other than glucose • Makes ATP via ATP synthase • Makes ATP via ATP synthase
• Uses an electron transport chain • Uses an electron transport chain
• Relies on membrane protein complexes • Relies on membrane protein complexes

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Key concepts

1. Energy conversions are measured using Gibbs free energy changes

2. Gibbs free energy depends on enthalpy and entropy

3. Metabolic reactions can be endergonic (energy requiring) or exergonic (energy releasing).

4. Usually ATP provides the energy for endergonic reactions this and is the cell’s ‘energy shuttle’

5. Endergonic reactions in cells can be coupled to exergonic reactions (usually ATP hydrolysis) to
allow them to proceed

6. Energy is generated by breakdown of glucose through glycolysis and the citric acid cycle

7. The electron transport chain provides a chemiosmotic gradient of H+ that drives ATP synthesis

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