21.

4 Strategies of Metabolism: ATP and Energy Transfer

thehands
arestoring
E

• ATP has three phosphate groups.

• Removal of one of the –PO4 groups by
hydrolysis gives adenosine diphosphate –
ADP. ATP ADP releasesenergy

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21.4 Strategies of Metabolism: ATP and Energy Transfer

usedtohydrolyzethe bond to releasephosphate
reactants produits phosphate
ATP + H2O ➝ ADP + Pi ΔG = –7.3 kcal/mol
1É ÉÉne
other
ADP + Pi ➝ ATP + H2O
I um ma n
I
ΔG = +7.3 kcal/mol
a endersonic thereneeds
page to e an input of
input E to makeATP stoneenergy
ATP ADD there is a release ofE

• ATP is an energy transporter because its

production from ADP requires an input of
energy that is then released wherever the
reverse reaction occurs.

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 21.4 Strategies of Metabolism: ATP and Energy Transfer

• The hydrolysis of ATP to give ADP and its

reverse, the phosphorylation of ADP, are
reactions perfectly suited to their role in
metabolism.
• The stored energy is released only in the ATPdoes notturn
into ADP on its
presence of the appropriate enzymes. own there is an

• A useful amount of energy is released when enzyme that

regulates thisAxn
a phosphoryl group is removed from it by
usingH2o
to break hydrolysis. Pi
bond
• If too much energy was involved,
interconversion would be more difficult.
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21.5 Strategies of Metabolism:

Metabolic Pathways and Coupled Reactions
• The overall free-energy change for any series of A B
reactions can be found by summing up the free- as
energy changes for the individual steps. I
• Not every step in a metabolic pathway is downhill.
• Energetically unfavorable reactions are coupled to
energetically favorable reactions so that the overall
is
Rx one
The same time to energy change is favorable. as fit
allow the • Coupling allows the energy stored in one chemical
overall an
compound be transferred to other compounds. hatpfsf.FIIny
to be
energetically • Excess energy is released as heat and contributes atria
favorable to maintaining body temperature.

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 21.5 Strategies of Metabolism:
Metabolic Pathways and Coupled Reactions
important to know what mn areowning P getsadded to ADP
to form Atp
t
sexismican
ans
endersmic
Rxn2

a exersonic

Ht theenergy of the men

Rn i t an 2 Hopo
4,0 gets cancelled out when
cnet.fiariiiimaiij
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we add the nonstormer
jgi

21.6 Strategies of Metabolism:

Oxidized and Reduced Coenzymes
• Many metabolic reactions are oxidation–reduction
reactions. theyneed to our the same time
i • A steady supply of oxidizing and reducing agents must
E be available. this allows the Axn to be coupled
up • A few coenzymes cycle continuously between their
oxidized and reduced forms.

theagent are
always reactants
If
in the run It Eat
Reduced and reducingagent
causes anothereleven
oxidited refer to be reduced
to element contains

than
© 2013 Pearson Education, Inc.

Edited
element
 21.6 Strategies of Metabolism:
Oxidized and Reduced Coenzymes

important
• Oxidation can be loss of electrons, loss of alcohol aldehyde

forstudents hydrogen, or addition of oxygen. OH H

to be • Reduction can be gain of electrons, gain of
1
oxidation
able to hydrogen, or loss of oxygen.
evaluate
Axn • Oxidation and reduction always occur together.
• Each increase in the number of carbon–oxygen
bonds is an oxidation, and each decrease in the
number of carbon–hydrogen bonds is a
reduction.

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21.6 Strategies of Metabolism:

Oxidized and Reduced Coenzymes
Reductionhappens here while
it allows anotheroxiditing

I in angent An Impute has an extrati

adding
that means c Hbond
some partof
The molecule
is reduced fhhkffanedasn.ie
gasen sina.is sent
• Nicotinamide adenine dinucleotide and its phosphate are
coenzymes that enter and leave enzyme active sites in
which they are required for redox reactions.
• As oxidizing agents they remove hydrogen from a
substrate, and as reducing agents (NADH and NADPH)
they provide hydrogen that adds to a substrate.
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 21.6 Strategies of Metabolism:
Oxidized and Reduced Coenzymes
in this an malate getsoxidized
Dimpled
any Nadt NAD getsreduced
coenzyme
the
D 1 12PM
y entyre
turnintokitchen
what Lenture
penning
• The oxidation of malate to oxaloacetate requires the
removal of two hydrogen atoms to convert a secondary
alcohol to a ketone.
NAD
• The oxidizing agent, which will be reduced during the
reaction, is NAD+ functioning as a coenzyme for the
enzyme malate dehydrogenase.
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21.6 Strategies of Metabolism:

Oxidized and Reduced Coenzymes
• A hydrogen atom is equivalent to a hydrogen ion, H+ plus
an electron, e–.
• Flavin adenine dinucleotide (FAD), another common
oxidizing agent, is reduced by the formation of covalent
bonds to two hydrogen atoms to give FADH2.
Iii

FAD causesanotherelement to be oxidized as aresultFAD is

reduced
© 2013 Pearson Education, Inc.
 21.6 Strategies of Metabolism:
Oxidized and Reduced Coenzymes

• Because reduced coenzymes have picked up

electrons (in their bonds to hydrogen) that are
passed along in subsequent reactions, they
are often referred to as electron carriers. e
trans.laliater

• As coenzymes cycle through their oxidized

and reduced forms, they also carry energy
Is Inapter
along from reaction to reaction.

• Ultimately, this energy is passed on to the

bonds in ATP.
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21.7 The Citric Acid Cycle

• The acetyl groups in acetyl-SCoA

molecules are readily removed in an
energy-releasing hydrolysis reaction.
usingH2oto breakbonds
yens n
catfff.sn
2C molecule
regenerate

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 21.7 The Citric Acid Cycle

• Oxidation of 2 carbons to give CO2 and

transfer of energy to reduced coenzymes
occurs in the citric acid cycle.

• This is also known as the tricarboxylic acid

cycle (TCA) or Krebs cycle.

• The citric acid cycle is a closed loop of

reactions in which the product of the final
step, oxaloacetate, is the reactant in the
first step.
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21.7 The Citric Acid Cycle

stepisdescribed

8Reactions
substrate

went.mg
produn

what is happening
eachstep of rxn
namesof reactant
products of step

effthe Enzymes responsible

for eachstep
if there is a creature
eastep
© 2013 Pearson Education, Inc.
 21.7 The Citric Acid Cycle

actions
STEPS 1 and 2:
– Acetyl groups enter the cycle at Step 1
III
by addition to 4-carbon oxaloacetate to step
give citrate, a 6-carbon intermediate.
OHisbonded
to a brand to
– Citrate is a tertiary alcohol and cannot
3other C be oxidized; it is converted in Step 2 to sep2
alcoholCutrate
its isomer, isocitrate, a secondary
alcohol that can be oxidized to a ketone.
The isomerization is catalyzed by
Cy in isomeitation
aconitase.
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21.7 The Citric Acid Cycle

STEPS 3 and 4:
– Both steps are oxidations that rely on NAD+
i as the oxidizing agent.
EE
– One CO2 leaves at Step 3 as the —OH group
of isocitrate is oxidized to a keto group. step
E.IE
iiiii – A second CO2 leaves at Step 4, and the
story
resulting succinyl group is added to coenzyme
A. In both steps, electrons and energy are

III transferred. NAD NADH Ht

– Succinyl-CoA carries four carbon atoms along
to the next step.

© 2013 Pearson Education, Inc.

 21.7 The Citric Acid Cycle

STEP 5:
regenerated
– The 4-carbon oxaloacetate must be restored
for Step 1 of the next cycle.

nm
– The exergonic conversion of succinyl-CoA to
succinate is coupled with phosphorylation of
energy GDP to give GTP. GTP is similar in structure
is.IEaEn
succinate
to ATP and, like ATP, carries energy.

ftp – In many cells, GTP is directly converted to

ATP. Step 5 is the only step in the cycle that
generates an energy-rich triphosphate.

© 2013 Pearson Education, Inc.

21.7 The Citric Acid Cycle

STEP 6:
– Succinate from Step 5 is oxidized by removal
of two hydrogen atoms to give fumarate. twoH are removed
– The enzyme for this reaction, succinate from survinate
to form a
dehydrogenase, is part of the inner doublebondin

Remy
I mitochondrial membrane. fumerate
– The reaction requires FAD, which is
covalently bound to its enzyme.
– Succinate dehydrogenase and FAD pass
electrons directly into electron transport.
– Step 6 neither uses nor releases energy.
© 2013 Pearson Education, Inc.
 21.7 The Citric Acid Cycle

STEPS 7 and 8:
– Water is added across the double bond of step7
qq.gg fumarate to give malate (Step 7).
– Oxidation of malate, a secondary alcohol, steps
ain
gives oxaloacetate (Step 8).

© 2013 Pearson Education, Inc.

21.7 The Citric Acid Cycle

• The rate of the citric acid cycle is controlled by the
body’s need for ATP and coenzymes.
b c E isused
• When energy is being used at a high rate, ADP
accumulates and activates isocitrate dehydrogenase,
the enzyme for Step 3. generatemore E

• When the body’s supply of energy is abundant,

NADH is present in excess and acts as an inhibitor of
isocitrate dehydrogenase. NADHinhibitsthe enzymein sep3

• The cycle is activated when energy is needed and

inhibited when energy is in good supply.

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 21.8 The Electron-Transport Chain and ATP Production

• At the conclusion of the citric acid cycle,

the reduced coenzymes are ready to
donate their energy to making ATP. e transportchain

• The energy is released in a series of

oxidation–reduction reactions that move
electrons from one carrier to the next.

• Each reaction in the series is exergonic.

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21.8 The Electron-Transport Chain and ATP Production

• The sequence of reactions is known as the electron- generateNADH

transport chain (also the respiratory chain). EHE.fm
• The enzymes and coenzymes of the chain are embedded
in the inner membrane of the mitochondrion.

lotsofH ionssoto movemore

9
I fp e ations it will
require E
e gothrough
the e
transportinainft
e comesbackoutwhenATP isformed
© 2013 Pearson Education, Inc.

NADH NADT lose Ht and e

 21.8 The Electron-Transport Chain and ATP Production

• As electrons move down the electron-transport Ht tomes ye

pathway, the energy is used to move hydrogen ions
from the matrix into the intermembrane space.

• Because the inner membrane is otherwise

impermeable to the H+ ion, the result is a higher H+
concentration in the intermembrane space than in
the mitochondrial matrix.

• Moving ions from a region of lower concentration to

one of higher concentration requires energy to
make it happen.

• This energy is recaptured for use in ATP synthesis.

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21.8 The Electron-Transport Chain and ATP Production

• Electron transport proceeds in four enzyme

complexes in fixed positions within the inner
membrane of mitochondria, and two electron
carriers that move from one complex to another.
• The four fixed complexes are very large
assemblages of polypeptides and electron
acceptors. Electron acceptors are generally
cytochromes or quinones.

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 21.8 The Electron-Transport Chain and ATP Production

• Each of complexes I–IV contain

several electron carriers.
• Hydrogen ions and electrons
move through the pathway in
the direction of the arrow.
• Each complex is at a lower
energy level than the preceding.
• Plant cells contain mitochondria
and chloroplasts. Chloroplasts
carry out photosynthesis, a
series of reactions that also
involve an electron transport
chain.
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21.8 The Electron-Transport Chain and ATP Production

• Hydrogen ions can return to the matrix by

passing through a channel that is part of the
ATP synthase enzyme complex.
• In doing so, they release the potential energy
gained as they were moved against the
concentration gradient.
• This energy release drives the phosphorylation
of ADP.
• Recent research suggests that each NADH
molecule yields about 2.5 molecules of ATP
and that each FADH2 molecule yields
approximately 1.5 molecules of ATP. Emma

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 21.8 The Electron-Transport Chain and ATP Production

Blockers and Uncouplers of Oxidative Phosphorylation

• Cyanide and barbiturates are among a group of
substances that block respiration (oxidative
phosphorylation) at the cytochromes in the
electron-transport chain, with different blockers
acting on different cytochromes.
• Other substances allow electron transport to
occur but prevent the conversion of ADP to ATP
by ATP synthase. When ATP production is
severed from energy use, it is said that ATP
production is uncoupled from the energy of the
proton gradient.

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