Andrew Drinnan

School of BioSciences

and@unimelb.edu.au
 Energy
• Chemical and energy transformations in cells
– Metabolism

• Sequence of chemical reactions

– metabolic pathways

• Energy is the capacity to do work

– potential energy is stored energy
– kinetic energy is expressed as movement

• Energy transformations are governed by the laws

of thermodynamics
-Complex systems requires energy
– Energy is conserved
 Harvesting Chemical Energy
•  Organisms convert chemical energy of fuel
molecules to useable energy in the form of
adenosine triphosphate (ATP)
–  ATP is used to drive cellular processes
•  Energy is released along metabolic (catabolic)
pathways
–  carbohydrates processed by glycolysis
–  lipids processed by β–oxidation
•  Products of pathways act as substrates for cellular
respiration
•  Glycolysis, Fermentation, Krebs Cycle, Electron
Transport Chain
Adenosine triphosphate ATP
Energy released from an exergonic reaction is used to
phosphorylate ADP, which is then dephosphorylated to
drive an endergonic reaction
 Enzymes
Enzymes are biological catalysts that lower
the activation energy in reactants (substrates)
 • Enzyme catalyzed reactions require less activation energy
Energy released Energy supplied • They proceed thousands of times faster

Uncatalyzed

Activation
energy Catalyzed
Activation
energy
Reactant Reactant

Product Product

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 Enzyme Catalytic Cycle

1 The substrate, sucrose, consists

of glucose and fructose bonded together. Glucose Fructose
2 The substrate binds to the
enzyme, forming an enzyme-
Bond substrate complex.
4 Products are
H 2O released, and
the enzyme is
free to bind
other
Active site 3 The binding of the substrates.
substrate and enzyme
places stress on the
Enzyme glucose-fructose bond,
and the bond breaks.

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Electron transport pathways
•  Enzymes for particular pathways are often physically
linked - substrate channelling
•  Electrons are transferred from donor to acceptor
–  molecule that loses electron is oxidised
–  molecule that gains electron is reduced
•  Transfer reactions are oxidation–reduction reactions
(redox)
Overview of Cellular Respiration
 Glycolysis: initial processing of glucose
•  Occurs in the cytosol
•  Glycolysis is a net producer of energy
3
1 2
6-carbon glucose
(Starting material)
2 ATP

P P P P

6-carbon sugar diphosphate 6-carbon sugar diphosphate

P P P P

3-carbon sugar 3-carbon sugar 3-carbon sugar 3-carbon sugar

phosphate phosphate phosphate phosphate
NADH NADH
2 ATP 2 ATP

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3-carbon 3-carbon
pyruvate pyruvate
 Mitochondria
•  Mitochondria evolved from engulfed
prokaryotes

•  Mitochondria are the site of cellular

respiration
–  release energy by oxidation of sugars and
lipids
–  released energy stored in ATP
–  cells with high level of metabolic activity have
large numbers of mitochondria
Mitochondria

double membrane
 Mitochondria
We couldn t live for 2 minutes
without them, yet even after a
billion years mitochondria behave
as if things might not work out
between us. They maintain their
own DNA, RNA and ribosomes.
They reproduce at a different time
from us. They look like bacteria
and divide like them too. They
even suffer a little when we dose
ourselves with antibacterials.
Mitochondria don t even speak
the same genetic language as us.
In short they keep their bags
packed. It is like having a
stranger in your house, but one
who s been there for a billion
years . - Bill Bryson, A short history of nearly
everything, 2003
Krebs cycle: completing the
oxidation of fuels
 Krebs Cycle
(also known as the citric acid cycle, TCA cycle)
pyruvate
1 NADH 2 3
CoA–
(Acetyl-CoA)

4-carbon molecule 4-carbon molecule

(Starting material) 6-carbon 6-carbon molecule (Starting material)
molecule NADH
NADH
CO2 FADH2

4-carbon 5-carbon
molecule molecule 4-carbon molecule

NADH
ATP
CO2

Krebs turns twice for each glucose molecule

(once for each of the 2 pyruvates)
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NADH is a temporary electron carrier
NAD+ +2H <=> NADH + H +

NAD+ and FAD are recycled

Glucose

Glycolysis
Electron Transport Chain
Pyruvate
oxidation
Intermembrane space

Krebs
cycle H+ H+ H+ Inner
mitochondrial
membrane
Electron transport
chain C

Q
e–
e– e–
FADH2

NADH + H+ 2H+ + ½O2

NAD+ H 2O
NADH Cytochrome
dehydrogenase bc1 complex oxidase complex

Mitochondrial matrix
Electron Transport Chain
 Chemiosmosis
Intermembrane space
H+ H+

H+ H+
H+ Inner
mitochondrial
membrane

ADP + Pi
NAD+

NADH H+
ATP
Proton pump ATP
synthase
Mitochondrial matrix
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Action of ATP synthase
– channel allows H+ to move freely down
electrochemical gradient
– movement is source of energy for ATP
synthesis

ATP synthase visualized using atomic force microscopy

www.biologie.uni-osnabrueck.de/biophysik/Junge/pictures/Synthase.MOV

Matrix

NADH > NAD+

Intermembrane space

mitochondrion
 Overview of ATP Synthesis
Slide number: 1
Intermembrane space
Pyruvate from
cytoplasm Inner H+
H+
mitochondrial
membrane Electron
transport
system
C
Q

NADH
H+
1. Electrons are harvested 2. Electrons provide
and carried to the transport energy to pump
Acetyl-CoA system. protons across the
membrane.
NADH
H 2O
Krebs 1
FADH2 3. Oxygen joins with O2
cycle 2 O2
protons to form water.
2H+
C02
32 ATP
4. Protons diffuse back H+
in, driving the synthesis
2 ATP of ATP.

Channel
protein
Mitochondrial matrix

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 Overview of ATP Synthesis
Slide number: 2
Intermembrane space
Pyruvate from
cytoplasm

Mitochondrial matrix

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 Overview of ATP Synthesis
Slide number: 3
Intermembrane space
Pyruvate from
cytoplasm

NADH

Acetyl-CoA

Mitochondrial matrix

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 Overview of ATP Synthesis
Slide number: 4
Intermembrane space
Pyruvate from
cytoplasm

NADH

Acetyl-CoA

NADH

Krebs
FADH2
cycle

CO2

2 ATP

Mitochondrial matrix

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 Overview of ATP Synthesis
Slide number: 5
Intermembrane space
Pyruvate from
cytoplasm Inner
mitochondrial
membrane

NADH

1. Electrons are harvested

and carried to the transport
Acetyl-CoA system.

NADH

Krebs
FADH2
cycle

CO2

2 ATP

Mitochondrial matrix

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
 Overview of ATP Synthesis
Slide number: 6
Intermembrane space
Pyruvate from
cytoplasm Inner
mitochondrial
membrane

NADH

1. Electrons are harvested

and carried to the transport
Acetyl-CoA system.

NADH

Krebs
FADH2
cycle

CO2

2 ATP

Mitochondrial matrix

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
 Overview of ATP Synthesis
Slide number: 7
Intermembrane space
Pyruvate from
cytoplasm Inner H+
H+
mitochondrial
membrane Electron
transport
system
C
Q

NADH
H+
1. Electrons are harvested 2. Electrons provide
and carried to the transport energy to pump
Acetyl-CoA system. protons across the
membrane.
NADH

Krebs
FADH2
cycle

CO2

2 ATP

Mitochondrial matrix

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
 Overview of ATP Synthesis
Slide number: 8
Intermembrane space
Pyruvate from
cytoplasm Inner H+
H+
mitochondrial
membrane Electron
transport
system
C
Q

NADH
H+
1. Electrons are harvested 2. Electrons provide
and carried to the transport energy to pump
Acetyl-CoA system. protons across the
membrane.
NADH
H 2O
Krebs 1
FADH2 3. Oxygen joins with O2
cycle 2 O2
protons to form water.

CO2

2 ATP

Mitochondrial matrix

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
 Overview of ATP Synthesis
Slide number: 9
Intermembrane space
Pyruvate from
cytoplasm Inner H+
H+
mitochondrial
membrane Electron
transport
system
C
Q

NADH
H+
1. Electrons are harvested 2. Electrons provide
and carried to the transport energy to pump
Acetyl-CoA system. protons across the
membrane.
NADH
H 2O
Krebs 1
FADH2 3. Oxygen joins with O2
cycle 2 O2
protons to form water.
2H+
CO2
32 ATP
4. Protons diffuse back H+
in, driving the synthesis
2 ATP of ATP.

Channel
protein
Mitochondrial matrix

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Theoretical ATP Yield
Glucose

2 ATP
ATP Glycolysis

2 NADH 4 ATP
Pyruvate

2 NADH 6 ATP
Acetyl-CoA

2 ATP

Krebs 6 NADH 18 ATP

cycle
2 FADH2 4 ATP

40% of energy
Total net ATP yield = 36 ATP
in glucose
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β-oxidation: initial processing of lipids

•  Lipids hydrolysed into free fatty acids and

glycerol
–  fatty acids are substrate for β-oxidation

•  β-oxidation takes place inside mitochondria

–  energy from C–C bond conserved in C–H bond in
acetyl CoA
–  acetyl CoA enters citric acid cycle

–  Produces FADH2 and NADH

 Fermentation
• ATP can be produced in absence of
oxygen (Glycolysis)
– additional reactions reduce the pyruvate
produced in glycolysis and recycle NADH
to NAD+
• End products
– lactate (animals, bacteria)
– ethanol (plants, yeast)
Fermentation

Recycles NADH

Eduard Buchner: 1907 Nobel Prize in Chemistry

Ethanol fermentation

In the absence of oxygen,

yeast convert pyruvate (from
glucose) to ethanol

CO2 is produced as a
byproduct

If you stir (oxygenate) your

home brew the yeast will
revert to the Krebs Cycle and
Electron Transport Chain,
producing water not alcohol
 Phosphagen system

Cellular ATP reserves are good

for about 3 seconds

Cellular creatine phosphate can

be quickly converted to ATP

Good for about 10 seconds

100m sprint run on the

phosphagen system
 Glycolysis
Glycolysis kicks in as
creatine phosphate is
exhausted.

Krebs and ETC too slow,

and blood supply can t
maintain sufficient cellular
oxygen levels

It is good for about 90

seconds (400m)

Gasping after strenuous

exercise is necessary to
repay the Oxygen debt
Substrate supply problem
Marathon runners have fitness
finely tuned to oxidative
respiration

They often hit the wall at the 2

hour (32 km) stage when
glycogen supplies are exhausted
and glycolysis is unable to
proceed
Do I have to know
all that?

Only the red bits!