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Cellular Respiration: Harvesting Chemical Energy
Overview: Life Is Work
• Living cells require energy from outside sources
• Energy flows into an ecosystem as sunlight and
leaves as heat
• Photosynthesis generates O2 and organic
molecules, like sugars, which are used in cellular
respiration
Light
energy
ECOSYSTEM
Photosynthesis
in chloroplasts
CO2 + H2O
Organic
+O
molecules 2
Cellular respiration
in mitochondria
ATP
Energy currency of cell
ATP powers most cellular work
Heat
energy
How do organisms get energy?
 autotroph: from
the ambient
 heterotroph: from
other organisms
4
heterotroph organisms
• Heterotrophs organisms cannot fix
inorganic carbon, therefore
use organic carbon fixed by
autotroph for growth.
heterotroph organisms
• Heterotrophs can be further divided
based on how they obtain energy; if
the heterotroph uses light for energy,
(it happens mainly in some groups of
bacteria) then it is considered a
photoheterotroph, while if the
heterotroph uses chemical energy, it
is considered a chemoheterotroph.
Overview: Life Is Work
• Animals, such as the giant panda, obtain
energy by eating plants, and some animals
feed on other organisms that eat plants.
food chain
chemical energy
Energy is stored in the covalent bonds of molecules.
Combustion is an redox reaction that release energy
from complex organic molecules, releasing energy,
and organic molecules like carbon dioxide and
water.
The Principle of Redox
• Chemical reactions that transfer electrons
between reactants are called oxidation-reduction
reactions, or redox reactions
• Oxidation and reduction always occur together.
The Principle of Redox
• In oxidation, a substance loses electrons, or is
oxidized
• In reduction, a substance gains electrons, or is
reduced (the amount of positive charge is
reduced)
• The electron donor is called the reducing agent
• The electron receptor is called the oxidizing
agent
Reactants
Products
becomes oxidized
becomes reduced
Methane
(reducing
agent)
Oxygen
(oxidizing
agent)
Carbon dioxide
Water
NAD+
Nicotinamide Adenine
Dinucleotide Plus, a redox
coenzyme and energy
carrier.
Stepwise Energy Harvest via NAD+
(and the Electron Transport Chain)
• In cellular respiration, glucose and other organic
molecules are broken down in a series of steps.
• Electrons from organic compounds are usually
first transferred to NAD+, to produce NADH
NAD+ + H + + 2 eNADH
NAD+ = oxidized form
NADH = reduced form
FAD (flavin adenine dinucleotide)
• FAD is the oxidized form of
another redox coenzyme.
• FAD can accepts two electrons
and two protons to become
FADH2, the reduced form.
The Principle of Redox
• NAD+ and FAD are oxidizing agents.
• The transfer of electrons during chemical reactions
releases energy stored in organic molecules.
• This released energy is ultimately used to
synthesize ATP
ATP
Adenosine triphosphate
ATP
Adenosine triphosphate is a coenzyme
used for intracellular energy transfer.
catabolism
Catabolism is the set of metabolic
pathways that breaks complex molecules
into smaller units.
Organic fuels get oxidized.
These reactions release energy, alas they
are exoergonic.
Anabolism is the opposite process.
Catabolic Pathways and Production of ATP
• Fermentation is a partial degradation of sugars,
to produce ATP, that occurs without O2
• Aerobic respiration consumes organic
molecules and O2 and yields ATP
• Anaerobic respiration is similar to aerobic
respiration but consumes compounds other
than O2
cellular respiration
• Cellular respiration includes both aerobic and
anaerobic respiration, but is often used to
refer to aerobic respiration.
aerobic cellular respiration
• 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
Energy = ATP + heat
• During cellular respiration, the fuel (such as
glucose) is oxidized, and O2 is reduced.
becomes oxidized
becomes reduced
Dehydrogenase
• Several processes are central to cellular
respiration and related pathways
The Three Stages of Cellular Respiration
–Glycolysis (breaks down glucose into two
molecules of pyruvate)
–The citric acid cycle (completes the
breakdown of glucose)
–Oxidative phosphorylation (accounts for
most of the ATP synthesis)
Glycolysis occurs in the cytoplasm
Electrons
carried
via NADH
Glycolysis
Pyruvate
Glucose
Cytosol
ATP
Sugar is splitted into two molecules
of pyruvate, some ATP and NADH
produced.
Substrate-level
phosphorylation
Citric Krebs Cycle occurs in the matrix of the
mitochondrion.
Electrons carried
via NADH and
FADH2
Electrons
carried
via NADH
Citric
acid
cycle
Glycolysis
Pyruvate
Glucose
Mitochondrion
Cytosol
Pyruvate is broken down
into CO2, some ATP,
NADH and FADH2 is
produced.
ATP
ATP
Substrate-level
phosphorylation
Substrate-level
phosphorylation
Oxidative phosphorylation occurs in the cristae of the
mitochondrion
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
H2O is used to oxidize the NADH & FADH2 produced in
previous steps, producing O2 and lots of ATP
cellular respiration efficency
• From the complete combustion of one mole of
glucose 686 kcal are released.
• The metabolic energy efficiency of cellular
respiration (the energy that can be used to
produce ATP) is about 40% (263 kcal), with the
additional 60% of the energy given off as heat.
how much ATP is produced?
• Biology textbooks often state that from 36 to
38 ATP molecules are produced during cellular
respiration .
ATP phosphate bond has 7.3 kcal/mol of energy (36 X 7.3 = 263 kcal/mol)
how much ATP is produced?
However, this maximum yield is never quite
reached due to metabolic losses (leaky
membranes, energy used to transport of reagents into
the mitochondrial matrix), and current estimates
range around 29 to 32 ATP per glucose.
• Oxidative phosphorylation accounts for almost
90% of the ATP generated by cellular respiration
• A smaller amount of ATP is formed in
glycolysis and the citric acid cycle by
substrate-level phosphorylation
Enzyme
Enzyme
ADP
P
Substrate
+
Product
ATP
glycolysis
Glycolysis harvests chemical energy by
oxidizing glucose to pyruvate
• Glycolysis (“splitting of sugar”) breaks down
glucose into two molecules of pyruvate
• Glycolysis occurs in the cytoplasm and has two
major phases:
– Energy investment phase
– Energy payoff phase
Section 9-1
Energy investment phase
Glucose
Energy payoff phase
2 Pyruvic acid
To the electron
transport chain
Requirements for Glycolysis
• Glucose (6C)
• 2 ATP (as activation energy), 4 ADP, 2 NAD+
• Enzymes
The Products of Glycolysis
• 2 of Pyruvate (ionized form of Pyruvic Acid) (3C)
• 2 ADP, 4 ATP, 2 NADH
Pyruvic acid
pyruvic acid / pyruvate
The name of the ionized form of an organic acid
is made by replacing the suffix -ic with -ate
Glucose is phosphorilated
by ATP, then rearranged by
an isomerase enzyme,
then phosphorilated again
by ATP.
The fructose 1,6bisphophate produced is
then broken into two
molecules of G3P,
(glyceraldehyde 3phosphate).
energy investment phase
Each G3P is oxidized by
NAD+, so 2 NADH are
produced. After, part of
the energy of the
intermediate organic
molecules is captured
inside 2 molecules of
ATP (total: 4 ATP).
In the end, two
molecule of pyruvate
are left.
energy payoff phase
Glycolysis Result
In summary, glycolysis takes one glucose and
turns it into
2 pyruvate,
2 NADH
and a net of 2 ATP (4 ATP -2 ATP)
Glycolysis: a closer look
G3P
3-phosphosfoglicerate 3PG
from glycolysis to Krebs cycle
• In the presence of O2, pyruvate enters the
mitochondrion
CYTOSOL
MITOCHONDRION
NAD+
NADH
+ H+
2
1
Pyruvate
Transport protein
3
CO2
Coenzyme A
Acetyl CoA
Coenzyme A (CoA)
from pyruvate to acetyl CoA
• Inside the mitochondrion (before the citric acid
cycle can begin), pyruvate (3C) must be
decarboxylated into acetate (2C), then oxidized
and joined to a molecule of Coenzyme A, and so
converted to acetyl CoA, which links the cycle to
glycolysis.
acetyl CoA
During the transformation process of pyruvate
into acetyl CoA , a molecule of CO2 is released
and a molecule of NADH is produced.
acetate
acetyl CoA
mithocondrion structure
endosymbiosis theory
mitochondrial DNA
mtDNA inheritance
citric acid cycle
The citric acid cycle completes the
energy-yielding oxidation of organic
molecules
• The citric acid cycle, also called the Krebs cycle,
oxidizes organic fuel derived from pyruvate,
generating , for every turn:
1 ATP
3 NADH
 1 FADH2
• The citric
acid cycle has
eight steps,
each
catalyzed by
a specific
enzyme
Pyruvate
CO2
NAD+
CoA
NADH
+ H+
Acetyl CoA
CoA
CoA
Citric
acid
cycle
2 CO2
FADH2
3 NAD+
3 NADH
FAD
+ 3 H+
ADP + P
ATP
i
Acetyl CoA
CoA—SH
1
Oxaloacetate
Citrate
Citric
acid
cycle
First step: the acetyl group of acetyl CoA (2C)
joins the cycle by combining with oxaloacetate
(4C), forming citrate (6C).
The CoA is released.
acetyl CoA (2C) react with oxaloacetate (4C)
forming citrate (6C). CoA is released.
Acetyl CoA
CoA—SH
H2O
1
Oxaloacetate
2
Citrate
Isocitrate
Citric
acid
cycle
• The next seven steps decompose, little by
little, the citrate (6C) back to oxaloacetate
(4C), making the process a cycle.
Acetyl CoA
CoA—SH
1
H2O
Oxaloacetate
2
Citrate
Isocitrate
NAD+
Citric
acid
cycle
3
NADH
+ H+
CO2
-Ketoglutarate
• The NADH and FADH2 produced during the cycle
will carry the electrons extracted from the
organic molecules to the electron transport
chain.
Acetyl CoA
CoA—SH
1
H2O
Oxaloacetate
2
Citrate
Isocitrate
NAD+
Citric
acid
cycle
NADH
+ H+
3
CO2
CoA—SH
-Ketoglutarate
4
NAD+
Succinyl
CoA
CO2
NADH
+ H+
• Two of CO2 exit the cycle on every turn.
Acetyl CoA
CoA—SH
1
H2O
Oxaloacetate
• A molecule of
ATP is produced
on every turn of
the cycle.
2
Citrate
Isocitrate
NAD+
Citric
acid
cycle
NADH
+ H+
3
CO2
CoA—SH
-Ketoglutarate
4
CoA—SH
5
NAD+
Succinate
Pi
GTP GDP
ADP
ATP
Succinyl
CoA
NADH
+ H+
CO2
Acetyl CoA
CoA—SH
• A molecule of
FADH2 is
produced on
every turn of the
cycle.
H2O
1
Oxaloacetate
2
Citrate
Isocitrate
NAD+
Citric
acid
cycle
Fumarate
NADH
+ H+
3
CO2
CoA—SH
6
-Ketoglutarate
4
CoA—SH
5
FADH2
NAD+
FAD
Succinate
Pi
GTP GDP
ADP
ATP
Succinyl
CoA
NADH
+ H+
CO2
Acetyl CoA
CoA—SH
H2O
1
Oxaloacetate
2
Malate
Citrate
Isocitrate
NAD+
Citric
acid
cycle
7
H2O
Fumarate
NADH
+ H+
3
CO2
CoA—SH
6
-Ketoglutarate
4
CoA—SH
5
FADH2
NAD+
FAD
Succinate
Pi
GTP GDP
ADP
ATP
Succinyl
CoA
NADH
+ H+
CO2
• Step 8 of the citric acid cycle:
Acetyl CoA
CoA—SH
NADH
+H+
• Three of NADH are
produced on every
turn of the cycle.
H2O
1
NAD+
8
Oxaloacetate
2
Malate
Citrate
Isocitrate
NAD+
H2O
Citric
acid
cycle
7
Fumarate
NADH
+ H+
3
CO2
CoA—SH
6
-Ketoglutarate
4
CoA—SH
5
FADH2
NAD+
FAD
Succinate
Pi
GTP GDP
ADP
ATP
Succinyl
CoA
NADH
+ H+
CO2
into the cycle
Acetyl CoA (2C)
1 ADP
3 NAD+
1 FAD
out of the cycle
2 CO2
1 ATP
3 NADH
1 FADH2
Inputs
Outputs
S—CoA
C
2
ATP
6
NADH
O
CH3
2
Acetyl CoA
O
C
COO
CH2
COO
2
Citric acid
cycle
2 FADH2
Oxaloacetate
Starting from one molecule of glucose two of
acetyl-CoA are produced, so you have to double
the output.
Overall, the oxidation of one
glucose molecule yields:
And six molecules of CO2
What Are the Aerobic Pathways of
Glucose Catabolism?
• Pyruvate oxidation and the citric acid cycle are
regulated by concentrations of starting
materials.
• The starting molecules (acetyl CoA and
oxidized electron carriers) must be
replenished.
• The electron carriers are reduced and they
must be reoxidized.
• If O2 is present, it accepts the electrons and
H2O is formed.
During oxidative phosphorylation,
chemiosmosis couples electron
transport to ATP synthesis
• Following glycolysis and the citric acid cycle,
NADH and FADH2 account for most of the
energy extracted from food
electron transport
– Electrons from NADH and FADH2 pass through
the respiratory chain of membrane-associated
carriers.
– Electron flow results in a proton concentration
gradient across the inner mitochondrial
membrane, which powers ATP synthesis via
oxidative phosphorylation
Chemiosmosis
– Electrons flow back across the membrane
through a channel protein, ATP synthase,
which couples the diffusion with ATP synthesis.
H+
H+
H+
H+
Protein complex
of electron
carriers
Cyt c
V
Q



FADH2
NADH
ATP
synthase
FAD
2 H+ + 1/2O2
NAD+
H2O
ADP + P i
(carrying electrons
from food)
ATP
H+
1 Electron transport chain
Oxidative phosphorylation
2 Chemiosmosis
electron transport chain
• Why does the electron transport chain have so
many steps? Why not in one step?
• 2 NADH + 2 H+ + O2 → 2 NAD+ + 2 H2O
• This reaction is extremely exergonic; in an
uncontrolled one step reaction too much free
energy would be released all at once, an
explosive reaction that could not be harvested
by the cell.
• In a series of reactions, each releases a small
amount of energy that can be captured by an
endergonic reaction.
H2 + 1/2 O2
1/ O
2 2
2H
(from food via NADH)
2 H+ + 2 e–
Controlled
release of
energy for
synthesis of
ATP
Explosive
release of
heat and light
energy
1/ O
2 2
(a) Uncontrolled reaction
(b) Cellular respiration
• The respiratory chain is located in the cristae
of the inner mitochondrial membrane.
• Most of the chain’s components are proteins.
• Energy is released as electrons are passed
between carriers.
• The carriers
alternate reduced
and oxidized states
as they accept and
donate electrons.
• Electrons drop in
free energy as they
go down the chain
and are finally
passed to O2,
forming H2O
The Respiratory Chain and ATP
Synthase Produce ATP by a
Chemiosmotic Mechanism
The electron transport chain (transmembrane
protein complexes) and the ATP synthase in
the mitochondrion inner membrane.
Electrons are transferred from NADH or FADH2
to the electron transport chain.
Electrons are passed through a number of
proteins including cytochromes (each with an
iron atom).
NADH
50
2 e–
NAD+
FADH2
2 e–
40

FMN
FAD
Multiprotein
complexes
FAD
Fe•S 
Fe•S
Q

Cyt b
30
Fe•S
Cyt c1
I
V
Cyt c
Cyt a
Cyt a3
20
10
0
2 e–
(from NADH
or FADH2)
2 H+ + 1/2
O2
H2O
The chain’s function is to break the large freeenergy drop from food to O2 into smaller steps
that release energy in manageable amounts.
In the last step electrons reduce O2 molecules.
electrons + oxygen ions + hydrogen ions = water
Electron transfer causes proteins to pump H+ from
the mitochondrial matrix to the intermembrane
space.
This is an example of chemiosmosis, the use of
energy in a gradient to drive cellular work.
INTERMEMBRANE SPACE
• The energy stored in a H+
gradient across a membrane
couples the redox reactions
of the electron transport
chain to ATP synthesis
• The gradient is referred
to as a proton-motive force,
emphasizing its capacity to
do work
H+
H+
Stator
Rotor
Internal
rod
Catalytic
knob
ADP
+
P
i
ATP
MITOCHONDRIAL MATRIX
H+ then moves back across the membrane,
passing through channels in ATP synthase
ATP synthase uses the exergonic flow to
drive phosphorylation of ATP
Figure 3.10 How ATP Is Made
• The structure and function of
ATP synthase is the same in
all living organisms.
• It is a molecular motor with two parts:
– F0 unit—the transmembrane H+ channel
– F1 unit—projects into mitochondrial matrix;
rotates to expose active sites for ATP
synthesis
• These molecular motors can make up to 100
ATP molecules per second.
• The mechanism was demonstrated by isolating the F1 unit and
attaching fluorescently labeled microfilaments to it.
• Although O2 is an excellent electron acceptor,
incomplete electron transfer can result in toxic
intermediates.
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
yield
• About 40% of the energy in a glucose molecule
is transferred to ATP during cellular respiration.
• A theoretical yield of 36-38 ATP molecules can
be produced, but in reality the yield is lower,
about 30-32 ATP molecules.
Electron shuttles
span membrane
CYTOSOL
2 NADH
6 NADH
2 NADH
Glycolysis
2
Pyruvate
Glucose
MITOCHONDRION
2 NADH
or
2 FADH2
2
Acetyl
CoA
+ 2 ATP
Maximum per glucose:
2 FADH2
Citric
acid
cycle
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
+ 2 ATP
+ about 32 or 34 ATP
About
36 or 38 ATP
From a molecule of NADH 2,5-3 molecules of
ATP can be produced.
From a molecule of FADH2 1,5-2 molecules of
ATP can be produced.
tutorials
https://www.youtube.com/watch?v=-Gb2EzF_XqA
Glycolysis and the citric acid cycle
connect to many other metabolic
pathways
• Gycolysis and the citric acid cycle are major
intersections to various catabolic and anabolic
pathways
The Versatility of Catabolism
• Catabolic pathways funnel electrons from many
kinds of organic molecules into cellular
respiration
• Glycolysis accepts a wide range of
carbohydrates
• Proteins must be digested to amino acids;
amino groups can feed glycolysis or the citric
acid cycle
• Fats are digested to glycerol (used in glycolysis)
and fatty acids (used in generating acetyl CoA)
• Fatty acids are broken down by beta oxidation
and yield acetyl CoA
• An oxidized gram of fat produces more than
twice as much ATP as an oxidized gram of
carbohydrate
Proteins
Carbohydrates
Amino
acids
Sugars
Fats
Glycerol
Glycolysis
Glucose
Glyceraldehyde-3-
NH3
P
Pyruvate
Acetyl CoA
Citric
acid
cycle
Oxidative
phosphorylation
Fatty
acids
Biosynthesis (Anabolic Pathways)
• The body uses small molecules to build other
substances
• These small molecules may come directly from
food, from glycolysis, or from the citric acid
cycle
Regulation of Cellular Respiration via
Feedback Mechanisms
• Feedback inhibition is the most common
mechanism for control
• If ATP concentration begins to drop, respiration
speeds up; when there is plenty of ATP,
respiration slows down
• 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
anaerobic respiration
• Many bacteria and archaea have evolved
pathways that allow them to exist where O2 is
scarce or absent, by using other electron
acceptors— anaerobic respiration.
Table 3.2