CELL

R E S P I R AT I O N
Siew Ee Ling, PhD
Senior Lecturer,
ASASIpintar Program,
Pusat Genius@Pintar Negara UKM
L E T ’ S T E S T YO UR S K I L L S !

at www.kahoot.it
 https://youtu.be/owXgZgULb4U

This hoary marmot (Marmota caligata) obtains energy for its cells by feeding on plants. In the process of cellular respiration,
mitochondria in the cells of animals, plants, and other organisms break down organic molecules, generating ATP and waste
products: carbon dioxide, water, and heat. Note that energy flows one way, but chemicals are recycled.
How is the chemical energy stored in food used to
generate ATP, the molecule that drives most cellular work?

• Plant and animal cells break down organic

molecules by cellular respiration in the
mitochondria
• The chemical energy in food is
transformed into chemical energy in ATP
• Some energy is released to the
environment as heat
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W H AT I S C E L L U L A R R E S P I R AT I O N ? ?
 Redox reactions
• Catabolic pathways produce
energy by oxidizing organic fuel
• Redox (reduction and oxidation)
– Transfer electrons from one
reactant to another by
oxidation and reduction
• In oxidation
– A substance loses electrons, or
is oxidized
• In reduction
– A substance gains electrons, or
is reduced
 Redox reactions
becomes oxidized
(loses electron)

Na + Cl Na+ + Cl–
becomes reduced
(gains electron)
Reactants Products

becomes oxidized

CH4 + 2O2 CO2 + Energy + 2 H2O

H becomes reduced

H H H
C
H
O O O C O O

Methane Oxygen Carbon dioxide Water

(oxidizing
(reducing
agent) agent)
“Lost” “Gained”
Figure 10.3 shared electrons shared electrons
 Redox reactions: Cellular
respiration

• During cellular respiration

– Organic fuel (glucose) is oxidized and oxygen is reduced

becomes oxidized

C6H12O6 + 6O2 6CO2+ 6H2O+ Energy

becomes reduced
∆G = -686 Kcal/mole
 Animation: Redox Reactions

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 Respiration
• 2 types Glucose

– Anaerobic (glycolysis → CYTOSOL

alcoholic
Pyruvate
fermentation/lactic acid
O2 present
fermentation) No O2 present
Fermentation Cellular respiration

– Aerobic (glycolysis →
Krebs/citric acid cycle →
MITOCHONDRION
Electron transport chain Ethanol Acetyl CoA
→ oxidative or
phosphorylation ) lactate
Citric
acid
cycle

Figure 9.18
 Cellular respiration is stepwise
• Electrons from organic compounds
– Are usually first transferred to NAD+, a coenzyme
2 e– + 2 H+
2 e– + H+
NAD+ NADH H+
H
O Dehydrogenase
H HO
2[H]
+ (from Reduction of NAD +
+ H+
C NH2 C NH2
N+ food) Oxidation of NADH N
Nicotinamide Nicotinamide
O CH2 (oxidized form) (reduced form)
O
O P O–
O H H
O P O– HO
HO
OH NH2
CH2
O N N Nicotinamide Adenine Dinucleotide (NAD+) Structure:
H
N N H 2 nucleotides
O 2 ribose
H
2 Phosphate group
H
HO OH nicotinamide (with 1 H)
Figure 10.4
 Energy shuttle of the cell: ATP
• Adenosine triphosphate
• Immediate E donor
• From respiration
• Small & H2O soluble
• Provides energy for:
– Anabolic reaction
– Active transport
– Cell division
– Movement
& a lot more.
 ATP hydrolysis powers cellular work
• Energy is released from ATP
– When the terminal phosphate bond is broken
– ∆G = -7.3 kcal/mol (-30.5 kJ/mol)
 NAD+: An electron carrier
• Nicotinamide adenine dinucleotide (NAD+)
• Derived from niacin
• Electron acceptor
• Cycles easily between NAD+(oxidized form)
and NADH (reduced form)
 NAD+: An electron carrier
• NADH → NAD+
– Loss of H atom
– NADH reductase (the 1st e- carrier in ETC)
– Inner mitochondria
– ≈ 3 ATP form per NADH (calculate this later in ETC!)
• H+ from NADH can be passed to dehydrogenase in cytoplasm such as
lactate dehydrogenase
NAD+→ NADH
NAD+ → NADH
FADH2
• Flavin adenine
dinucleotide
• Coenzyme
• Derivative of riboflavin
(vitamin B)
• FADH2 is a reduced form
of FAD+
• Structure
– flavin
– ribitol
– adenine
– 2P
– 2H
FAD → FADH2
Oxidized form

Reduced form
 FADH2 → FAD+
• FADH2 pass 2 H to coenzyme Q to become FAD+
• Coenzyme Q
• 2nd e- receptor in ETC in the inner membrane of mitochondria
• 2 ATP formed per FADH2 molecule (calculate this later in the ETC!)
• FADH2 is a prosthetic group bonded to succinate dehydrogenase
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 • The process that generates almost 90% of the ATP
is called oxidative phosphorylation because it is
powered by redox reactions
• Some ATP is also formed in glycolysis and the citric
acid cycle by substrate-level phosphorylation
• Substrate-level phosphorylation occurs when an
enzyme transfers a phosphate group directly from a
substrate to ADP

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 Cellular respiration:
stages & location
• Glycolysis, link reaction, Krebs cycle/citric acid cycle, Electron
transport chain/oxidative phosphorylation
• Glycolysis – cytoplasm
• Link reaction – matrix of mitochondria
• Krebs cycle – matrix of mitochondria
• Electron transport chain & Oxidative phosphorylation – inner
membrane of mitochondria
– Outer mitochondrial membrane→proton concentration builds up
 Glycolysis
Glucose glycolisis 2 Pyruvate + 2 ATP + 2 NADH

• 10 steps process
• Breakdown 1 molecule of glucose → 2x 3-C
molecules of pyruvate/pyruvic acid
• Releases 4 ATP
• Activation for glycolysis uses 2 ATP
• Net gain 2 ATP
• Where? → in cytoplasm
• No oxygen is used
• ATP produced by substrate level phosphorylation
– Phosphofructokinase (PFK) – allosteric enzyme
 Glycolysis Glycolysis Citric
acid
cycle
Oxidative
phosphorylation

ATP ATP ATP

• Consists of two major Energy investment phase

Glucose
phases
– Energy investment 2 ATP + 2 P 2 ATP used

phase Energy payoff phase

– Energy payoff phase 4 ADP + 4 P 4 ATP formed

2 NAD+ + 4 e- + 4 H + 2 NADH + 2 H+

2 Pyruvate + 2 H2O

Net
Glucose 2 Pyruvate + 2 H2O
4 ATP formed – 2 ATP used 2 ATP + 2 H+

2 NAD+ + 4 e– + 4 H + 2 NADH

Figure 10.8
Glycolysis
Energy investment
phase

Energy payoff phase

Energy investment phase

Energy payoff phase

 Energy-investment

Initial phase
• Phosphorylation of glucose to fructose bisphosphate
– 2 ATP needed
– Raise energy level of glucose
– Create high energy carbon-phosphate bond to gain more energy
 Energy-investment

Splitting Of fructose bisphosphate

• Fructose bisphosphate is split into 2 three-carbon sugars (triose
phosphates):
– phosphoglyceraldehyde/glyceraldehyde-3-phosphate (G3P)
– dihydroxy-acetone phosphate
• Both triose sugars are inter-convertible
 Energy-payoff

Formation of Pyruvate
• 2 triose phosphates undergo dehydrogenation – release 2 H
• 2 H accepted by 2 NAD+ to form 2 NADH
• 2 NADH is transported into mitochondria
• 4 ATP is produced
 ∑ Net
Glycolysis products

Glucose 2 Pyruvate +
2 H2O

4 ATP formed – 2 ATP used 2 ATP

2 NAD+ + 4e– + 4 H+ 2 NADH

 Pyruvate from glycolysis undergoes oxidative

Link
decarboxylation to form acetyl-Coenzyme A (acetyl co-A)

CO2 removed & dehydrogenation occur

reaction: Coenzyme A & NAD+ are needed to form acetyl co-A &

Pyruvate
NADH

NAD+ is reduced to NADH

oxidation Products: 2 NADH (from 2 pyruvates) + CO2 + Acetyl co-A

 Link reaction:
Pyruvate oxidation to acetyl co-A
CYTOSOL MITOCHONDRION

NAD+ NADH + H+
O–
S CoA
2
C O
C O

C O
CH3
1 3
CH3
Acetyl CoA
Pyruvate CO2 Coenzyme A

Transport protein

Figure 10.10
Hans Krebs who identified the citric acid
cycle - also known as the Krebs cycle - was
born on this day in 1900.
A German biochemist.
Received Noble Prize in Physiology or
Medicine in 1953 for this contribution. The
cycle is a series of reactions that convert
nutrients into other molecules with a large
amount of chemical energy.
 Krebs/citric acid cycle: overview
Pyruvate Glycolysis Citric
acid
Oxidative
cycle phosphorylation
(from glycolysis,
2 molecules per glucose)
ATP ATP ATP

CO2

CoA
NADH
+ 3 H+
Link reaction Acetyl CoA
CoA

CoA
Krebs cycle

Citric
acid 2 CO2
cycle
FADH2 3 NAD+

FAD 3 NADH
+ 3 H+
ADP + P i
ATP
Figure 10.11
The Citric Acid Cycle
The citric acid cycle, also called the Krebs cycle, oxidizes organic fuel
derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH2 per turn

Another 2 CO2 are produced as a waste product

Because 2 pyruvate are produced per glucose, the cycle runs twice per
glucose molecule consumed

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Formation of NADH, FADH2, GTP & ATP
• Formed in the processes of glycolysis, link reaction,
Krebs cycle
• 3 NADH per cycle
- 3 rxn when H + is removed during
dehydrogenation by dehydrogenases.
- NAD+ as coenzyme that accepts H+
• 1 FADH2 per cycle
- Succinate is dehydrogenated to fumarate by
succinate dehydrogenase
- Prosthetic group to succinate dehydrogenase
- Cofactor (organic cofactor; coenzyme) that accepts
2 H atoms
 Formation of NADH, FADH2, GTP & ATP
• GTP
– Guanine triphosphate ≈ ATP
– Substrate level phosphorylation from GDP & Pi to form GTP
– Is used to generate ATP
• 1 ATP per cycle
– Formed from GTP with transferase
– P group is transferred on ADP to form ATP
– Substrate level phosphorylation
 Take it home!
• Let’s sing: Glycolysis
https://youtu.be/4_wbKAxsKXQ
Figure 10.UN11

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 During oxidative phosphorylation,
chemiosmosis couples electron transport to
ATP synthesis

• Molecules of NADH and FADH2 produced during

glycolysis and the citric acid cycle account for most
of the energy extracted from glucose
• NADH and FADH2 donate electrons to the electron
transport chain, which powers ATP synthesis via
oxidative phosphorylation

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Figure 10.14

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 Electron transport chain (ETC)
• If electron transfer is not H2 + 1/2 O2
stepwise
– A large release of energy
occurs Explosive

Free energy, G
release of

– As in the reaction of hydrogen heat and light

energy

and oxygen to form water

Figure 9.5 A H2O

(a) Uncontrolled reaction

 Electron Transport Chain (ETC)
• Passes electrons 2H + 1/ O2
2
(from food via
NADH)
in a series of Controlled
release of
2 H+ + 2 e–
steps instead of in energy for
synthesis of
ATP
ATP
one explosive

Free energy, G
ATP

reaction ATP

• Uses the energy

from the electron 2
e–
1/
2
2 H+ O2
transfer to form
ATP H2O

Figure 9.5 B (b) Cellular respiration

Electron Transport Chain (ETC)
• Collection of proteins embedded in the cristae
membrane of mitochondria
• Carries out a series of redox reactions
• a.k.a cytochrome or respiratory chain
• Makes no ATP but sets the stages for ATP production
for chemiosmosis
• Source of e-: NADH & FADH2 from glycolysis & Krebs
• Thousand copies of ETC in a mitochondria
• As the proteins shuttle e-, they pump protons from
matrix → intermembrane space
 The Pathway of Electron Transport

Molecules of the electron

The membrane is folded In prokaryotes, the
transport chain are
into cristae to increase electron transport chain
embedded in the inner
surface area for electron is embedded in the
mitochondrial membrane
transport chains plasma membrane
in eukaryotic cells

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 • Most of the molecules in the electron transport
chain are proteins, which exist in multiprotein
complexes
• NADH and FADH2 donate electrons to different
electron acceptors early in the chain
• Electrons are passed through a number of carrier
molecules including several cytochromes
(proteins with heme groups containing an iron
atom)
• Electron carriers alternate between reduced and
oxidized states as they accept and donate
electrons

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 • Electrons drop in free energy as they are
transferred down the chain, finally passing to O2 to
form H2O
• The electron transport chain breaks the large free-
energy drop from glucose to O2 into smaller steps,
releasing energy in manageable amounts
• No ATP is produced directly by the chain

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 Chemiosmosis:
the energy coupling mechanism
• Coupling of electron transport to ATP synthesis
– Electron passed to ubiquinone → protein- cytochrome complex
bc1 complex → cytochrome c → cytochrome oxidase complex
• NADH & FADH2
– Carry e- from glycolisis & Krebs cycle
– Donate e- to the ETC, which powers ATP synthesis via oxidative
phosphorylation
– NADH oxidized to NAD+
– FADH2 passes e- to ubiquinone of ETC; reduced to FAD
• Cytochrome oxidase needs oxygen & H+ from inner
membrane → H2O
– O2 + 4 H+ +4 e- → 2H2O
• NADH delivers e- at a higher energy level than FADH2
– NADH→ 3 ATP ; FADH2 → 2 ATP
 Chemiosmosis:
the energy coupling mechanism
• ATP synthase
– Is the enzyme that Figure 10.14
INTERMEMBRANE SPACE A rotor within the
actually makes H+ H+
H+
membrane spins
clockwise when
H+ flows past
ATP H+ H+
it down the H+
gradient.
H+

– Powered by H+
H+
A stator anchored
in the membrane

gradient holds the knob

stationary.

A rod (for “stalk”)

extending into
the knob also
spins, activating
catalytic sites in
H+ the knob.
Three catalytic
sites in the
ADP stationary knob
+ join inorganic
Pi ATP
Phosphate to ADP
to make ATP.
MITOCHONDRIAL MATRIX
 An Accounting of ATP Production by Cellular
Respiration

• During cellular respiration, most energy flows in this

sequence:
glucose → NADH → electron transport chain →
proton-motive force → ATP
• About 34% of the energy in a glucose molecule is
transferred to ATP, making about 32 ATP
• The rest of the energy is lost as heat

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Figure 10.15

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 Animation: ATP Yield from Cellular Respiration

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 Respiration
• 2 types Glucose

– Anaerobic (glycolysis → CYTOSOL

alcoholic
Pyruvate
fermentation/lactic acid
O2 present
fermentation) No O2 present
Fermentation Cellular respiration

– Aerobic (glycolysis →
Krebs/citric acid cycle →
MITOCHONDRION
Electron transport chain Ethanol Acetyl CoA
→ oxidative or
phosphorylation ) lactate
Citric
acid
cycle

Figure 9.18
 Anaerobic Respiration
• Absent of oxygen
• Process: glycolysis, fermentation
• 2 types:
– Alcohol fermentation
– Lactic acid fermentation
• Fermentation can generate ATP as long as NAD+ is available to accept e-
 Alcohol Fermentation
• 2 types of anaerobes:
– Facultative anaerobes: tolerate the presence of O2
– Obligate anaerobes: cannot live in presence of O2
• Yeast is a facultative anaerobe that produces alcohol
• Glycolysis
• Glucose→ pyruvate
• Pyruvate, a final e- acceptor oxidizes NADH → NAD+
• NAD+/NADH is reused
• Krebs cycle does not occur because no oxidative phosphorylation
• Products: 2 Ethanol, 2 ATP, 2 CO2
 Ethanol produced by
• Pyruvate accumulate
• Stimulate production of pyruvate decarboxylase
• Convert into ethanal & CO2
• Ethanol dehydrogenase converts ethanal (acetaldyehyde) into
ethanol
• Ethanol is poisonous to cells
• Yeast can tolerate 10 % alcohol
• 2 ATP molecules produced
Figure 10.16a

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 Lactic Acid Fermentation
• Where? → In muscles
• Glycolysis occurs to produced pyruvate
• Accumulation of pyruvate changes into lactate/lactic acid
• Products: 2 ATP, 2 Lactate produced
• In humans: Cause muscle cramp – denature proteins & stops
the muscles from contracting
• Cori cycle in liver (excess Lactate → glucose)
• Repay oxygen debt
Figure 10.16b

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 Take home messages!
• Catabolic pathways produce energy by oxidizing organic fuels
• Glycolysis produce chemical energy by oxidizing glucose to
pyruvate
• After pyruvate is oxidized, Krebs/citric acid cycle completes the
energy-producing oxidation of organic molecules
• During oxidative phosphorylation, chemiosmosis couples
electron transport to ATP synthesis
• Fermentation enable cells to produce ATP without oxygen
Why do we need energy?
 Activity
• Define chemiosmosis and
explain how a gradient of
proton is established across
the inner mitochondrial
membrane?
T H A N K YO U