5/13/2013

Cellular Respiration
Chapter 9

You should be able to:

1. Explain in general terms how redox reactions
are involved in energy exchanges
2. Name the three stages of cellular respiration;
for each, state the region of the eukaryotic
cell where it occurs, the products that result,
& the major intermediate steps
3. In general terms, explain the role of the
electron transport chain in cellular respiration

4. Explain where and how the respiratory

electron transport chain creates a proton
gradient
5. Distinguish between fermentation and
anaerobic respiration
6. Distinguish between obligate and facultative
anaerobes

5/13/2013

o Energy flows into an ecosystem as sunlight

and leaves as heat
o Photosynthesis (Chapter 10) generates O2
and organic molecules, which are used in
Cellular Respiration
o Cells use chemical energy stored in organic
molecules to regenerate ATP, which powers
work

Fig. 9-2

Light
energy
ECOSYSTEM

Photosynthesis
in chloroplasts
CO2 + H2O

Organic
+O
molecules 2

Cellular respiration
in mitochondria

ATP
ATP powers most cellular work
Heat
energy

Catabolic Pathways & Production of ATP

o The breakdown of organic molecules is
exergonic
o Aerobic respiration consumes organic
molecules & O2 and yields ATP

o Anaerobic respiration is similar to aerobic

respiration, but consumes compounds other
than O2
o Fermentation is a partial degradation of
sugars that occurs without O2

5/13/2013

o Cellular respiration includes both aerobic

and anaerobic respiration, but is most often
used to refer to aerobic respiration
o Although carbohydrates, fats, and proteins
are all consumed as fuel, it is helpful to
trace cellular respiration with the sugar
Glucose:
C6H12O6 + 6 O2 6 CO2 + 6 H2O + Energy (ATP + heat)

The Principle of Redox

o Chemical reactions that transfer electrons
between reactants are called oxidation-reduction
reactions, or redox reactions
o In oxidation, a substance loses electrons, or is
oxidized
o In reduction, a substance gains electrons, or is
reduced (the amount of positive (+) charge is
reduced)
LEO goes GER
Losing Electrons is Oxidation
Gaining Electrons is Reduction

OIL RIG
Oxidation Is Loss
Reduction Is Gain

Fig. 9-UN1

becomes oxidized
(loses electron)
becomes reduced
(gains electron)

becomes oxidized
becomes reduced

5/13/2013

o The electron donor (Na, Xe-) is called the

reducing agent (causes reduction,
undergoes oxidation, loses electrons)

o The electron receptor (Cl, Y) is called the

oxidizing agent (causes oxidation,
undergoes reduction, gains electrons)

Redox: Electron Position

o Some redox reactions do NOT transfer
electrons, but change the electron sharing
in covalent bonds
o Change position in relation to the nuclei
o An example is the reaction between
methane and O2

Fig. 9-3

Reactants

Products

becomes oxidized

becomes reduced

Methane
(reducing
agent)

Oxygen
(oxidizing
agent)

Carbon dioxide

Water

When electrons are closer to electronegative nuclei, they have

less free energy
So when electrons are transferred to a more electronegative atom
(say, from C to O) energy is released-Exergonic Reaction

5/13/2013

Oxidation of Organic Fuel Molecules

During Cellular Respiration
During cellular respiration, the fuel (ex. the C in
glucose) is oxidized, and O2 is reduced:
becomes oxidized
becomes reduced

Stepwise Energy Harvest via NAD+ & the

Electron Transport Chain
o In cellular respiration, glucose and other organic
molecules are broken down in a series of steps
o Electrons (with protons) from organic compounds are
usually first transferred to NAD+, a coenzyme

e e
-

NAD+

NADH

o As an electron acceptor, NAD+ is an oxidizing agent

during cellular respiration
o Each NADH (the reduced form of NAD+) represents stored
energy that is tapped to synthesize ATP

o NAD+ w/o extra e-, NADH w/ extra e-

Hi! I am NADH! I
am the reduced
form of NAD+ and
will carry my e-s to
the ETC!

Hi! I am NAD+
(I have 1 more
proton than
electron)

e e
-

NAD+

NADH

NAD+
1 H+ drifts
away

NADH
Dehydrogenase
Hi! I am glucose
and I am going to
donate 2 e-s and
1 H+ to NAD+

Glucose total loss in the

presence of dehydrogenase
= 2 hydrogen atoms

The Electron Taxi Cab:

NAD+ to NADH

5/13/2013

Fig. 9-4

2 e + 2 H +

2 e + H +

H+

NADH
Dehydrogenase
Reduction of NAD+

NAD+

2[H]

+ H+
Oxidation of NADH
Nicotinamide
(reduced form)

Nicotinamide
(oxidized form)

2 Electrons & Protons from Glucose

2 es & 1 H+ to NAD+
1 H+ drifts away
Dehydrogenase removes a pair of H
atoms (2 es and 2 protons) from
glucose, oxidizing it. The enzyme
delivers the 2 es along w/ 1 proton to
NAD+ and the other H+ is released as a
H+ ion

Dehydrogenase

o NADH passes the electrons to the electron

transport chain
o Unlike an uncontrolled reaction, the electron
transport chain passes electrons in a series of
steps instead of one explosive reaction

o O2 pulls electrons down the chain in an energyyielding tumble

o The energy is used to regenerate ATP

Fig. 9-5

H2 + 1/2 O2

2H
(from food via NADH)
Controlled
release of
2 H+ + 2 e
energy for
synthesis of
ATP

1/

2 O2

Explosive
release of
heat and light
energy

How we power
the space shuttle
(a) Uncontrolled reaction

1/

2 O2

Same reaction but

occurs in stages
(b) Cellular respiration

5/13/2013

Overall e- movement in cellular respiration

GlucoseNADHelectron transport chainO2

The Stages of Cellular Respiration: A

Preview
o Cellular respiration has three stages:
o 1. Glycolysis (breaks down 1 glucose into 2
molecules of pyruvate)
o 2. The Citric Acid Cycle (completes the
breakdown of glucose)
o 3. Oxidative phosphorylation (accounts for
most of the ATP synthesis)

Electrons carried
via NADH and
FADH2

Electrons
carried
via NADH

Citric
acid
cycle

Glycolysis
Pyruvate

Glucose

Oxidative
phosphorylation:
electron transport
and
chemiosmosis

Mitochondrion
Cytosol

ATP

ATP

ATP

Substrate-level
phosphorylation

Substrate-level
phosphorylation

Oxidative
phosphorylation

PLEASE NOTE WHERE EACH OCCURS

5/13/2013

o The process that generates most of the ATP

is called oxidative phosphorylation
because it is powered by redox reactions
o Oxidative phosphorylation accounts for
almost 90% of the ATP generated by
cellular respiration
o A smaller amount of ATP is formed in
glycolysis & the citric acid cycle by
substrate-level phosphorylation
oBioFlix: Cellular Respiration

Substrate-Level Phosphorylation
oSome ATP is made by direct transfer of a phosphate group from
an organic substrate with more energy than ATP has to ADP, by
an enzyme
Enzyme

Enzyme

ADP
P
Substrate

ATP

Product

oThe ATP is more stable than the original molecule, so this is

spontaneous
oVersus oxidative phosphorylation which adds an inorganic
phosphate to ADP

Glycolysis harvests chemical energy

by oxidizing Glucose Pyruvate
o Glycolysis (splitting of sugar) breaks down
Glucose into 2 molecules of Pyruvate
o Glycolysis occurs in the cytoplasm (cytosol) and
has two major phases:
1. Energy investment phase
ATP is used to phosphorylate Glucose (2x)
2. Energy payoff phase
Substrate-Level Phosphorylation (4x)
Glucose (6 C) 2 Pyruvate (3 C) + 2 ATP (net)+ 2 NADH

o Glycolysis occurs whether or not O2 is present

5/13/2013

Fig. 9-8

Energy investment phase

Glucose

2 ADP + 2 P

2 ATP

used

4 ATP

formed

Energy payoff phase

4 ADP + 4 P

2 NAD+ + 4 e + 4 H+

2 NADH + 2 H+
2 Pyruvate + 2 H2O

Net
2 Pyruvate + 2 H2O

Glucose
4 ATP formed 2 ATP used

2 ATP

2 NAD+ + 4 e + 4 H+

2 NADH + 2 H+

Figure 9.9a

Glycolysis: Energy Investment Phase

ATP
Glucose

Fructose 6-phosphate

Glucose 6-phosphate
ADP

Phosphoglucoisomerase

Hexokinase

Figure 9.9b

Glycolysis: Energy Investment Phase

Fructose 6-phosphate

ATP

Fructose 1,6-bisphosphate
ADP

Phosphofructokinase

Aldolase 4

Dihydroxyacetone
phosphate

Glyceraldehyde
3-phosphate

Isomerase 5

To
step 6

5/13/2013

Figure 9.9c

Glycolysis: Energy Payoff Phase

2 ATP
2 NADH
+ 2 H

2 NAD

2 ADP

2
Triose
phosphate
dehydrogenase

Phosphoglycerokinase

2 Pi
1,3-Bisphosphoglycerate

3-Phosphoglycerate

Figure 9.9d

Glycolysis: Energy Payoff Phase

2 ATP
2 H2O
2

Phosphoglyceromutase

3-Phosphoglycerate

2 ADP
2

Pyruvate
kinase

Enolase

2-Phosphoglycerate

Phosphoenolpyruvate (PEP)

10

Pyruvate

Preparation of Pyruvate for the

Citric Acid Cycle
o In the presence of O2, pyruvate enters the
mitochondrion
o Before the citric acid cycle can begin, pyruvate
must be converted to acetyl CoA, which links the
cycle to glycolysis (note loss of CO2)
CYTOSOL

MITOCHONDRION
NAD+

NADH

H+

2
1
Pyruvate

3
CO2

Coenzyme A

Acetyl CoA

1. Pyruvates COO- which

is fully oxidized is
removed and given off
as CO2
2. 2C fragment is oxidized
forming acetate and eare transferred to
NAD+
3. CoA attaced to acetate
forming acetyl CoA

Transport protein

10

5/13/2013

The Citric Acid Cycle completes the energyyielding oxidation of organic molecules
Pyruvate

o The citric acid cycle,

(Krebs cycle), takes place
within the mitochondrial
matrix

CO2

NAD+

CoA

NAD
H+
H+

Acetyl
CoA CoA
CoA

o Oxidizes organic fuel

derived from pyruvate

Citric
acid
cycle

2 CO2

FADH2

3
NAD+
3 NADH
+ 3 H+

FAD

o Generates: 1 ATP, 3
NADH, and 1 FADH2 per
turn (per Acetyl CoA)

ADP
+

Pi

ATP

o The citric acid cycle has 8 steps, each catalyzed

by a specific enzyme
o The acetyl group of acetyl CoA joins the cycle by
combining with oxaloacetate, forming citrate
o The next 7 steps decompose the citrate back to
oxaloacetate, making the process a cycle
o The NADH and FADH2 (from FAD) produced by
the cycle relay electrons extracted from food to the
electron transport chain

Figure 9.12-1

Acetyl CoA
CoA-SH

Oxaloacetate

Citrate

Citric
acid
cycle

11

5/13/2013

Figure 9.12-2

Acetyl CoA
CoA-SH

H2O

Oxaloacetate
2

Citrate
Isocitrate

Citric
acid
cycle

Figure 9.12-3

Acetyl CoA
CoA-SH

H2O

Oxaloacetate
2

Citrate
Isocitrate
NAD

Citric
acid
cycle

NADH

+ H
CO2

-Ketoglutarate

Figure 9.12-4

Acetyl CoA
CoA-SH

H2O

Oxaloacetate
2

Citrate
Isocitrate
NAD

Citric
acid
cycle

NADH

+ H
CO2

CoA-SH

-Ketoglutarate
4

NAD

CO2

NADH

Succinyl
CoA

+ H

12

5/13/2013

Figure 9.12-5

Acetyl CoA
CoA-SH

H2O

Oxaloacetate
2

Citrate
Isocitrate
NAD

Citric
acid
cycle

NADH

+ H
CO2

CoA-SH

-Ketoglutarate
4
CoA-SH

5
CO2

NAD

Succinate

NADH

Pi

+ H

Succinyl
CoA

GTP GDP
ADP

ATP

Figure 9.12-6

Acetyl CoA
CoA-SH

H2O

Oxaloacetate
2

Citrate
Isocitrate
NAD

Citric
acid
cycle

NADH

+ H
CO2

Fumarate

CoA-SH

-Ketoglutarate
4

CoA-SH

FADH2

CO2

NAD

FAD

Succinate

NADH

Pi

+ H

Succinyl
CoA

GTP GDP
ADP

ATP

Figure 9.12-7

Acetyl CoA
CoA-SH

H2O

Oxaloacetate
2

Malate

Citrate
Isocitrate
NAD

H2O

Citric
acid
cycle

NADH

+ H
CO2

Fumarate

CoA-SH

-Ketoglutarate
4

CoA-SH

FADH2

NAD

FAD

Succinate

CO2

NADH

Pi
GTP GDP

Succinyl
CoA

+ H

ADP

ATP

13

5/13/2013

Figure 9.12-8

Acetyl CoA
CoA-SH

NADH
+ H

H2O

NAD

Oxaloacetate
2

Malate

Citrate
Isocitrate
NAD

H2O

Citric
acid
cycle

NADH

+ H
CO2

Fumarate

CoA-SH

-Ketoglutarate
4

CoA-SH

FADH2

NAD

FAD

Succinate
GTP GDP

CO2

NADH

Pi

Succinyl
CoA

+ H

ADP

ATP

We are through with the Glucose

molecule

But.
Remember all those high-energy
electrons taken by NAD+ & FAD?

During Oxidative Phosphorylation,

Chemiosmosis couples electron
transport to ATP synthesis
o NADH and FADH2 account for most of the
energy extracted from food
o These two electron carriers donate electrons
to the electron transport chain, which
powers ATP synthesis via oxidative
phosphorylation

14

5/13/2013

The Pathway of Electron

Transport
o The electron transport chain is in the cristae
of the mitochondrion
o Most of the chains components are proteins,
which exist in multiprotein complexes
o The carriers alternate reduced and oxidized
states as they accept & donate electrons
o Electrons drop in free energy as they go
down the chain and are finally passed to O2,
forming H2O

o Electrons are transferred from

NADH or FADH2 (from
glycolysis and citric acid cycle)
to the electron transport chain
o Electrons are passed through a
number of proteins including
cytochromes (each with an iron
atom) to O2
o The electron transport chain
generates no ATP
oThe chains function is to break the large free-energy
drop from food to O2 into smaller steps that release
energy in manageable amounts

Chemiosmosis:
The Energy-Coupling Mechanism

INTERMEMBRANE SPACE

o Electron transfer in the electron

transport chain causes proteins to pump
H+ (protons) from the matrix
intermembrane space (uphill)
o H+ then moves back across the
membrane (downhill), passing through
channels in ATP synthase
o ATP synthase uses the exergonic flow
of H+ to drive phosphorylation of ATP
o This is an example of chemiosmosis,
the use of energy in a H+ gradient to
drive cellular work

H+

Stator

Rotor

Internal
rod
Catalytic
knob
ADP
+
P

ATP

MITOCHONDRIAL MATRIX

15

5/13/2013

o The energy stored in a H+ gradient across a

membrane couples the redox reactions of
the electron transport chain to ATP
synthesis
o The H+ gradient is referred to as a
proton-motive force, emphasizing its
capacity to do work

H+

H+
H+

H+
Protein complex
of electron
carriers

Cyt c

ATP
synthase

FADH2
NADH

2 H+ + 1/2O2

H2O

FAD

NAD+

ADP + P i

(carrying electrons
from food)

ATP
H+

1 Electron transport chain

2 Chemiosmosis

Oxidative phosphorylation

Notice flow of e- from NADH and FADH2 to H2O

1.Electron transport and pumping of the protons (H+) create H+ gradient across the
membrane
2.ATP synthesis powered by flow of H+ back across the membrane

Accounting of ATP Production by

Cellular Respiration
o During cellular respiration, most energy
flows in this sequence:
glucose NADH electron transport
chain proton-motive force ATP
o About 34% of the energy in a glucose
molecule is transferred to ATP during
cellular respiration, making about 32 ATP
o There are several reasons why the number
of ATP is not known exactly

16

5/13/2013

Figure 9.16

Electron shuttles
span membrane

2 NADH

Glycolysis
2 Pyruvate

Glucose

MITOCHONDRION
2 NADH
or
2 FADH2
2 NADH

Pyruvate oxidation
2 Acetyl CoA

6 NADH

Citric
acid
cycle

2 ATP

2 ATP

Maximum per glucose:

2 FADH2

Oxidative
phosphorylation:
electron transport
and
chemiosmosis

about 26 or 28 ATP

About
30 or 32 ATP

CYTOSOL

Fermentation & Anaerobic Respiration

enable ATP without oxygen
o Most cellular respiration requires O2 to
produce ATP

o Glycolysis can produce ATP with or without

O2 (in aerobic or anaerobic conditions)
o In the absence of O2, glycolysis couples with
fermentation or anaerobic respiration to
produce ATP

Anaerobic respiration uses an electron

transport chain with a different electron
acceptor (other than O2).
Example: Sulfate (SO42-)

Fermentation uses phosphorylation instead

of an electron transport chain to generate
ATP

17

5/13/2013

Types of Fermentation
There must be a place to drop off electrons
from NADH, or all the NAD+ will be rapidly
used up
o Fermentation = Glycolysis + reactions that
regenerate NAD+, which can be reused by
glycolysis
o 2 common types are alcohol fermentation
and lactic acid fermentation
Animation: Fermentation Overview

o Alcohol fermentation--Pyruvate is converted to

ethanol in two steps, with the first releasing CO2

o Alcohol fermentation by yeast is used in brewing,

winemaking, and baking

o Lactic acid fermentation--Pyruvate is reduced

directly, forming lactate, with no release of CO2

oLactic acid fermentation by some fungi and bacteria is used to

make cheese and yogurt.
oHuman muscle cells use lactic acid fermentation to generate ATP
when O2 is scarce.

18

5/13/2013

Fermentation and Aerobic

Respiration Compared
o All use glycolysis (net ATP = 2) to oxidize glucose
and harvest chemical energy of food
o In all three, NAD+ is the oxidizing agent that
accepts electrons during glycolysis
o The processes have different final electron
acceptors: an organic molecule (such as pyruvate
or acetaldehyde) in fermentation and O2 in cellular
respiration
o Cellular respiration produces 32 ATP per glucose
molecule; fermentation produces 2 ATP per
glucose molecule

o Obligate anaerobes carry out fermentation

or anaerobic respiration and cannot survive
in the presence of O2
o Yeast and many bacteria are facultative
anaerobes--they can survive using either
fermentation or cellular respiration

Glucose

CYTOSOL

In a
facultative
anaerobe,
pyruvate is
a fork in the
metabolic
road that
leads to two
alternative
catabolic
routes

Glycolysis
Pyruvate

No O2 present:
Fermentation

O2 present:
Aerobic cellular
respiration

MITOCHONDRION
Ethanol
or
lactate

Acetyl CoA
Citric
acid
cycle

19

5/13/2013

The Evolutionary Significance of

Glycolysis
o Glycolysis occurs in nearly all organisms
o Glycolysis probably evolved in ancient
prokaryotes before there was oxygen in the
atmosphere
o Very little O2 was available in the
atmosphere until about 2.7 billion years ago,
so early prokaryotes likely used only
glycolysis to generate ATP
o Glycolysis is a very ancient process

Glycolysis & the Citric Acid Cycle

connect to many other metabolic
pathways
o Gycolysis & the Citric Acid Cycle are major
intersections to various catabolic and anabolic
pathways
o Many other Macromolecules can feed into these
pathways
oYou dont eat only Glucose
o Many things the cell and/or body needs are
originally part of these pathways (or can be
made from a chemical which is part of these
pathways)
oBut are shuttled off before the next
bioenergetic step

The Versatility of Catabolism

o Catabolic pathways funnel electrons from
many kinds of organic molecules into cellular
respiration
o Carbs: Glycolysis accepts a wide range of
carbohydrates
o Proteins must be digested to amino acids;
amino groups can feed glycolysis or the citric
acid cycle

20

5/13/2013

o Fats are digested to glycerol (used in glycolysis)

and fatty acids (used in generating acetyl CoA)
o Fatty acids are broken down by beta oxidation
and yield acetyl CoA

o An oxidized gram of fat produces more than twice

as much ATP as an oxidized gram of carbohydrate
Carbohydrate = 4 calories/gram
Fat
= 9 calories/gram
Why it is so much harder to lose weight eating a high fat so
much stored energy

Fig. 9-20

Proteins

Carbohydrates

Amino
acids

Sugars

Fats

Glycerol

Fatty
acids

Glycolysis
Glucose

Glyceraldehyde-3- P

NH3

Pyruvate

Acetyl CoA

Citric
acid
cycle

Oxidative
phosphorylation

Biosynthesis (Anabolic
Pathways)
o The body uses small molecules to build
other substances
o These small molecules may come directly
from food, from glycolysis, or from the citric
acid cycle

21

5/13/2013

Regulation of Cellular Respiration via

Feedback Mechanisms
o Feedback inhibition is the most common
mechanism for control
o If ATP concentration begins to drop,
respiration speeds up; when there is plenty
of ATP, respiration slows down
o Control of catabolism is based mainly on
regulating the activity of enzymes at
strategic points in the catabolic pathway

Fig. 9-21

Glucose
AMP
Glycolysis
Fructose-6-phosphate

Stimulates
+

Phosphofructokinase

Fructose-1,6-bisphosphate

Inhibits

Inhibits

Pyruvate
ATP

Citrate
Acetyl CoA

Citric
acid
cycle

Oxidative
phosphorylation

Figure 9.UN06

Inputs

Outputs
Glycolysis

Glucose

2 Pyruvate 2

ATP

2 NADH

22

5/13/2013

Figure 9.UN07

Outputs

Inputs

2 Pyruvate

2 Acetyl CoA
2 Oxaloacetate

Citric
acid
cycle

ATP

CO2

2 FADH2

NADH

23