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CHAPTER 7
RESPIRATION
Living cells require energy from outside
sources to perform tasks.
Energy enters most ecosystems as
sunlight and leaves as heat.(Figure 9.2, Campbell, page 160)
Photosynthesisgenerates O2 and organic
molecules that mitochondria of eukaryotes
use as fuel for cellular respiration.
Cells harvestchemical energy stored in
organic molecules and use it to regenerate
ATP, the molecule that drives most cellular
work.
3 pathways of respiration: glycolysis,
citric acid cycle, and oxidative
phosphorylation.
7.1 ATP (Adenosine Triphosphate) Immediate source of energy that drives
most cellular work.
Cells manage their energy resources to
do this work by energy coupling - use ofan exergonicprocess to drive anendergonic one.
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Endergonic Reaction - reaction thatends with a net gainin energy
Products have more energy than
reactants, e.g., photosynthesis
Exergonic Reaction - reactionthat ends with a net lossin energy
Reactants have more energy than
products, e.g., cellular respiration
Structure and hydrolysis of ATP
ATP = Nucleotide with unstable
phosphate bonds that cell hydrolyzes for
energy to drive endergonic reactions.
Consists ofadenine, ribose, & chain ofthree phosphate groups.
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Unstable bonds between phosphate
groups can be hydrolyzed in an exergonic
reaction.
When terminal phosphate bond is
hydrolyzed, a phosphate group is removed
producing ADP (adenosine diphosphate).
ATP + H2O ADP + Pi Under standard lab conditions, reaction
releases -31 kJ/mol (-7.3 kcal/mol). In living cell, reaction releases -55 kJ/mol
(-13 kcal/mol) - 77% more than under
standard conditions.
Terminal phosphate bonds of ATP are
unstable, so:
Products of hydrolysis reaction are morestable than reactants.
Hydrolysis of phosphate bonds is thus
exergonic as system shifts to a more
stable state.
How ATP performs work Exergonic hydrolysis of
ATP is coupled with endergonic processes
by transferring a phosphate group to
another molecule.
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Phosphate transfer is enzymatically
controlled.
Molecule receiving phosphate
(phosphorylated or activated
intermediate) becomes more reactive.
Example,
conversion of glutamic acid (Glu) to
glutamine (Gln):
Glu + NH3Gln
G = +14.2 kJ/mol (+3.4 kcal/mol)(endergonic)
Two step process of energy coupling
with ATP hydrolysis:
1. Hydrolysis of ATP and phosphorylation ofglutamic acid.
Glu + ATP Glu-(Pi) + ADPUnstable
phosphorylatedintermediate
2. Replacement of the phosphate with thereactant ammonia.
Glu-(Pi) + NH3 Gln + (Pi)Overall G:
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Glu + NH3Gln G = +14.2 kJ/molATP ADP + Pi G = -31.0 kJ/mol
Net G = -16.8 kJ/mol (Overall process is exergonic)
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The regeneration of ATP
ATP is continually regenerated by cell.
Process is rapid (107 molecules used and
regenerated/sec/cell).
Reaction is endergonic.
ADP + Pi ATP
G = + 31 kJ/mol (+7.3 kcal/mol)
Energy to drive endergonic regeneration
of ATP comes from exergonic process of
cellular respiration.
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7.2 Aerobic RespirationPreview of cellular respiration(See Figure 9.6, Campbell, page 164)
Stages of respiration: glycolysis, citric
acid cycle, and electron transport chain
and oxidative phosphorylation.
Glycolysis - in cytoplasm. Glucose broken down into two molecules
of pyruvate.
Citric acid cycle - in mitochondrialmatrix.
Completes breakdown of glucose by
oxidizing a derivative of pyruvate to CO2.
Several steps in glycolysis and citric acid
cycle are redox reactions - dehydrogenase
enzymes transfer electrons from substrates
to NAD+, forming NADH.
NADH passes electrons to electron
transport chain (ETC). Electrons then move from molecule to
molecule until they combine with molecular
O2 and H+ to form water.
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As they are passed along chain, energy
carried by electrons is transformed in
mitochondrion into a form that can be used
to synthesize ATP via oxidativephosphorylation. Inner membrane of mitochondrion is site
of electron transport and chemiosmosis,
processes that together constitute
oxidative phosphorylation.
Oxidative phosphorylation produces
almost 90% of ATP generated by
respiration.
Some ATP is formed directly during
glycolysis and citric acid cycle by
substrate-level phosphorylation. Enzyme transfers phosphate group from
an organic substrate to ADP, forming
ATP. (See Figure 9.7, Campbell, page 164)
For each molecule of glucose degraded to
CO2 & H2O by respiration, cell makes up to
38 ATP, each with 7.3 kcal/mol of free
energy.
Respiration uses small steps in
respiratory pathway to break large
denomination of energy contained in
glucose into the small change of ATP.
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Quantity of energy in ATP is more
appropriate for level of work required in
cell.
7.2.1 Glycolysis(See Figure 9.9, Campbell, page 166 - 167)
Glucose is split into two 3C sugars.
3C sugars oxidized and rearranged to
form two molecules of pyruvate, ionizedform of pyruvic acid.
Two phases of glycolysis:(Figure 9.8, Campbell, page 165)
1. Energy investment phase
Cell invests ATP to provide activation
energy by phosphorylating glucose.
Requires 2 ATP per glucose.
2. Energy payoff phase
ATP produced by substrate-levelphosphorylation.
NAD+ reduced to NADH by electronsreleased by oxidation of glucose.
Net yield from glycolysis is 2 ATP and 2
NADH per glucose.
No CO2 is produced during glycolysis.
Glycolysis can occur in presence or
absence of O2.
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The Glycolytic Pathway(Figure 9.9, Campbell, page 166 167)
http://www.db.uth.tmc.edu/faculty/alevine/1521_2000/glydetail.htm
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Overall reaction showing allreactants
and products resulting from glycolysis.
Glucose + 2ATP +2Pi + 4ADP + 2NAD
+2 Pyruvate + 2ADP +2ATP + 2NADH + 2H+ +
2H2O
Equation showing netreaction of
glycolytic pathway.
Glucose + 2Pi + 2ADP+ 2NAD+
2 Pyruvate + 2ATP +2NADH + 2H+ + 2H2O
7.2.2 Pyruvate oxidation(Figure 9.10, Campbell, page 168)
More than three-quarters of original
energy in glucose is still present in the two
molecules of pyruvate.
If O2 is present, pyruvate enters
mitochondrion where enzymes of citric acid
cycle complete its oxidation to CO2.
After pyruvate enters mitochondrion via
active transport, it is converted to acetyl
coenzyme A (acetyl CoA).
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This is accomplished by multienzyme
complex that catalyzes three reactions:
1. Carboxyl group is removed as CO2.2. Remaining 2C fragment is oxidized to
acetate. An enzyme transfers the pair of
electrons to NAD+ to form NADH.
3. Acetate combines with coenzyme A toform the very reactive molecule acetyl
CoA.
Acetyl CoA is now ready to feed its acetyl
group into the citric acid cycle for further
oxidation.
7.2.3 The Krebs cycle/ Citric Acid Cycle(Figure 9.12, Campbell, page 169)
Cycle oxidizes organic fuel derived from
pyruvate.
Acetyl group of acetyl CoA joins cycle by
combining with oxaloacetate, forming
citrate.
Citrate regeneraterd back (via several
steps) to OAA.
Three CO2 molecules are released,
including the one released during the
conversion of pyruvate to acetyl CoA.
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Cycle generates one ATP per turn by
substrate-level phosphorylation.
GTP molecule is formed by substrate-
level phosphorylation.
GTP used to synthesize an ATP, the only
ATP generated directly by cycle.
Most of chemical energy is transferred to
NAD+ and FAD during redox reactions.
Reduced coenzymes NADH and FADH2then transfer high-energy electrons to
electron transport chain.
For every acetyl CoA, each cycle
produces:
(i) 1 ATP by substrate-level
phosphorylation(ii) 3 NADH, and
(iii) 1 FADH2
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http://chemistry.gsu.edu/glactone/PDB/Proteins/Krebs/Krebs.html
Summary:
Acetyl CoA + 3 NAD+
+ FAD + ADP + Pi
+2H2O
2 CO2 + CoA-SH +
3NADH + 3H+ +
FADH2 + ATP
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7.2.4 Electron transport chain (oxidative
phosphorylation)
Only 4 of 38 ATP produced by respiration
of glucose are produced by substrate-level
phosphorylation:
Glycolysis 2 ATP.
Citric acid cycle 2 ATP.
NADH and FADH2 account for the majority
of energy extracted from food.
These reduced coenzymes link glycolysis
and citric acid cycle to oxidative
phosphorylation, which uses energy
released by ETC to power ATP synthesis.
The Pathway of Electron Transport(Figure 9.13, Campbell, page 171)
ETC is a collection of molecules
embedded in cristae.
Most components of ETC are proteins
bound to prosthetic groups. Electrons drop in free energy as they
pass down ETC.
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During electron transport along ETC,
electron carriers alternate between
reduced and oxidized states as they accept
and donate electrons.
Each component of chain becomes
reduced when it accepts electrons from
its uphill neighbor, which is less
electronegative.
It then returns to its oxidized form as itpasses electrons to its more
electronegative downhill neighbor.
Electrons carried by NADH are
transferred to the first molecule in ETC, a
flavoprotein.
Electrons continue along chain thatincludes several cytochrome proteins andone lipid carrier.
Prosthetic group of each cytochrome is a
heme group with an iron atom that
accepts and donates electrons.
Last cytochrome of chain, cyt a3, passesits electrons to oxygen, which is very
electronegative.
Each oxygen atom also picks up a pair of
H+ from aqueous solution to form water.
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For every two electron carriers (four
electrons), one O2 molecule is reduced to
two molecules of water.
Electrons carried by FADH2 have lower
free energy and are added at a lower
energy level than those carried by NADH.
ETC provides about one-third less energy
for ATP synthesis when electron donor is
FADH2 rather than NADH. ETC generates no ATP directly.
Its function is to break the large free
energy drop from food to oxygen into a
series of smaller steps that release energy
in manageable amounts.
How does the mitochondrion couple
electron transport and energy release to
ATP synthesis?
Chemiosmosis.
Chemiosmosis: Energy-CouplingMechanism(Figure 9.14, Campbell, page 171)
1. NADH delivers two electrons and two
protons to the first protein complex (I) in
cytochrome system located in cristae.
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2. Complex uses energy released from
electrons to actively pump H+ from matrix
to inter-membrane space.
3. Process is done two more time times.
Electrons are passed through two more
protein complexes (III & IV) which
transport two more H+ across membrane.
4. After passing through three protein
complexes, electrons combine with oneoxygen atom and two H+ to form water.
5. This transport across membrane produces
a concentration gradient with more H+ on
one side of membrane than the other. The
H+ gradients that results is referred to as
a proton-motive force. This gradient isused to make ATP.
6. Cristae membrane is very impermeable to
H+ except through a special protein called
ATP synthase. As protons pass through
this protein, energy is obtained to make
ATP from ADP & Pi.7. FADH2 delivers its electron via protein
complex II and so results in fewer
electrons being into the inter-membrane
space.
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Oxidative phosphorylation = Electrontransport + chemiosmosis.
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7.2.5 Calculations of Total ATPProduction by Cellular Respiration
Products generated when cellularrespiration oxidizes a molecule of glucose
to 6 CO2 molecules:(Figure 9.16, Campbell, page 173)
Conversions
NADH in cytoplasm produces 2 or 3 ATPby oxidative phosphorylation depending on
shuttle system used to transport electrons
from cytosol into mitochondrion:
If electrons are passed to FAD, e.g. brain
cells, 2 ATP are produced.
If electrons are passed to NAD+, e.g. liver
cells & heart cells, 3 ATP are produced.
NADH in mitochondria produces 3 ATP.
FADH2 adds its electrons to the electron
transport system at a lower level than
NADH, so it produces 2 ATP.
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http://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%20101/Bio%20101%20Lectures/Energy/energy.htm#NAD+http://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%20101/Bio%20101%20Lectures/Energy/energy.htm#ATP%20(adenosine%20triphosphate)http://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%20101/Bio%20101%20Lectures/Energy/energy.htm#FADhttp://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%20101/Bio%20101%20Lectures/Energy/energy.htm#FADhttp://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%20101/Bio%20101%20Lectures/Energy/energy.htm#NAD+http://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%20101/Bio%20101%20Lectures/Energy/energy.htm#ATP%20(adenosine%20triphosphate)http://faculty.clintoncc.suny.edu/faculty/Michael.Gregory/files/Bio%20101/Bio%20101%20Lectures/Energy/energy.htm#FAD -
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Glycolysis
Substrate-level phosphorylation = 2 ATP
2 NADH = 2 x 2 ATP = 4 ATP; or= 2 x 3 ATP = 6 ATP
Formation of Acetyl CoA
2 NADH = 2 x 3 ATP = 6ATP
Krebs Cycle
6 NADH = 6 x 3 ATP = 18 ATP
2 FADH2 = 2 x 2 ATP = 4 ATP
Substrate-level phosphorylation = 2 ATP
Total Yield
Glycolysis = 2 ATP
Aerobic respiration = 34 or 36 ATP
5. Summary
Pathway Substrate-level
phosphorylation
Oxidative
phosphorylation
Total
ATP
Glycolysi
s
2 ATP 2 NADH = 4-6 ATP 6 - 8
Coa 2 NADH = 6 ATP 6
Krebs
cycle
2 ATP 6 NADH = 18 ATP
2 FADH2 = 4 ATP
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Total 4 ATP 32 34 ATP 36-38
How efficient is respiration in generating
ATP?
Complete oxidation of glucose releases
686 kcal/mol.
Phosphorylation of ADP to form ATP
requires at least 7.3 kcal/mol.
Efficiency of respiration
= 7.3 kcal/mol x 38 ATP/glucose x 100%
686 kcal/mol glucose
= 40%.
60% of energy from glucose lost as
heat.
Some of that heat is used to maintainour high body temperature (37C).
Cellular respiration is remarkably
efficient in energy conversion.
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7.3 Anaerobic respiration Without oxygen, oxidative
phosphorylation ceases. Through fermentation, some cells can
oxidize organic fuel and generate ATP
without use of O2.
Anaerobic catabolism of sugars can
occur by fermentation. Fermentation generate ATP from glucose
by substrate-level phosphorylation as long
as there is a supply of NAD+ to accept
electrons.
If NAD+ pool is exhausted, glycolysis
shuts down. Under aerobic conditions, NADH transfers
its electrons to ETC, recycling NAD+.
Under anaerobic conditions, various
fermentation pathways generate ATP by
glycolysis and recycle NAD+ by transferring
electrons from NADH to pyruvate orderivatives of pyruvate.
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7.3.1 Ethanol fermentation(Figure 9.17 (a), Campbell, page 173)
In alcohol fermentation, pyruvate isconverted to ethanol in two steps.
1.Pyruvate converted to acetaldehyde (2C),
by removal of CO2.
2.Acetaldehyde reduced by NADH to
ethanol.
Alcohol fermentation by yeast - brewingand winemaking.
7.3.2 Lactic fermentation(Figure 9.17 (b), Campbell, page 173)
Pyruvate is reduced directly by NADH toform lactate without release of CO2.
Lactic acid fermentation by some fungi
and bacteria is used to make cheese and
yogurt.
Human muscle cells switch from aerobic
respiration to lactic acid fermentation togenerate ATP when O2 is scarce.
The waste product, lactate, may cause
muscle fatigue, but ultimately it is
converted back to pyruvate in the liver.
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Fermentation and Cellular RespirationCompared Similarities both use
1. Glycolysis to oxidize sugars to
pyruvate with a net production of 2 ATP
by substrate-level phosphorylation.
2. NAD+ as an oxidizing agent to
accept electrons from food duringglycolysis.
Difference
1. Mechanism for oxidizing NADH to NAD+.
Fermentation - electrons of NADH are
passed to an organic molecule toregenerate NAD+.
Respiration - electrons of NADH are
ultimately passed to O2, generating
ATP by oxidative phosphorylation.
2. ATP generated per molecule of glucose.
Aerobic respiration: 36 - 38 ATP.
Anaerobic respiration: 2 ATP.
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Facultative Anaerobes Makes ATP by aerobic respiration ifO2 is
present but can switch to fermentation inabsence ofO2.
Example: Yeast and many bacteria &
human muscle cells (at a cellular level).
Aerobic conditions: pyruvate is converted
to acetyl CoA and oxidation continues in
the citric acid cycle.
Anaerobic conditions: pyruvate serves as
an electron acceptor to recycle NAD+.
Evolutionary Significance of Glycolysis Oldest bacterial fossils are more than 3.5billion years old, appearing long before
appreciable quantities of O2 accumulated in
atmosphere.
Therefore, first prokaryotes may have
generated ATP exclusively from
glycolysis. The fact that glycolysis is the most
widespread metabolic pathway and occurs
in cytosol without membrane-enclosed
organelles suggests that glycolysis evolved
early in history of life.
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Fats must be digested to glycerol and
fatty acids.
Glycerol can be converted to G3P, an
intermediate of glycolysis.
Energy-rich fatty acids are split into 2C
fragments via beta oxidation. These molecules enter citric acid cycle
as acetyl CoA.
Biosynthesis (Anabolic Pathways) Intermediaries in glycolysis and citric
acid cycle can be diverted to anabolic
pathways.
Example, human cell can synthesize
about half the 20 different amino acids bymodifying compounds from citric acid
cycle.
Glucose can be synthesized from
pyruvate,
Fatty acids from acetyl CoA.
Glycolysis and citric acid cycle functionas metabolic interchanges that enable cells
to convert one kind of molecule to another.
Example, excess carbohydrates and
proteins can be converted to fats through
intermediaries of glycolysis and citric
acid cycle.
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Feedback mechanisms control cellularrespiration Basic principles of supply and demandregulate metabolic economy.
If cell has excess of a certain amino acid,
it uses feedback inhibition to prevent
intermediates from citric acid cycle being
synthesized to that amino acid.
Rate of catabolism also regulated by ATP
level in cell.
If ATP levels drop, catabolism speeds up
to produce more ATP.
Control of catabolism is based mainly on
regulating activity of enzymes at strategic
points in catabolic pathway.
One strategic point occurs in 3rd step of
glycolysis, catalyzed by allosteric enzyme,
phosphofructokinase.
Catalyzes earliest step that irreversiblycommits the substrate to glycolysis.
Inhibited by ATP and stimulated by AMP
(derived from ADP).
When ATP levels are high, inhibition of
this enzyme slows glycolysis.
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As ATP levels drop and ADP and AMP
levels rise, enzyme becomes active
again and glycolysis speeds up.
Citrate is also an inhibitor of
phosphofructokinase.
Synchronizes rate of glycolysis and citric
acid cycle.
If intermediaries from citric acid cycle
are diverted to other uses (e.g., amino acidsynthesis), glycolysis speeds up to replace
these molecules.