27

General, Organic, and

Biochemistry, 8e
Bettelheim,Brown,
Campbell, & Farrell

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27-1
27Chapter 27 Bioenergetics
Acetyl -CoA CoA

H + + N AD H

N AD + Citric
N AD +
acid
cycle
(8 s teps) N AD H + H +
FAD H2 CoA CO 2
FAD N AD +
N AD H + H +
GTP
GDP CO 2

How the Body Converts Food to Energy.

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27Metabolism
• Metabolism: the sum of all chemical reactions
involved in maintaining the dynamic state of a
cell or organism.
• Pathway: a series of biochemical reactions.
• Catabolism: the biochemical pathways that are
involved in generating energy by breaking down large
nutrient molecules into smaller molecules with the
concurrent production of energy.
• Anabolism: the pathways by which biomolecules are
synthesized.

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27Metabolism
• Metabolism is the sum of catabolism and anabolism.
Catabolism Anabolis m
Polysac-
Triglycerides charides Proteins
Catabolism Excretion
beakdown
of larger
Fatty acids Monosac- Amino
molecules Products of anabolism,
and glycerol charides Acids
to s maller including proteins and
ones nucleic acids
Small Anabolis m energy and
molecules of proteins reducing
oxidation and the agents
release of energy Some nutrients and
Excretion Anabolis m products of catabolism

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27Cells and Mitochondria
• Animal cells have many components, each with
specific functions; some components along with
one or more of their functions are:
• Nucleus: where replication of DNA takes place.
• Lysosomes: remove damaged cellular components and
some unwanted foreign materials.
• Golgi bodies: package and process proteins for
secretion and delivery to other cellular components.
• Mitochondria: organelles in which the common
catabolic pathway takes place in higher organisms; the
purpose of this catabolic pathway is to convert the
energy stored in food molecules into energy stored in
molecules of ATP.
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27A Rat Liver Cell
• FIGURE 27.2 A rat liver cell.

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27A Mitochondrion
• Figure 27.3(a) Schematic of a mitochondrion cut
to reveal its inner organization.

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27Common Catabolic Pthwy
• The two parts to the common catabolic pathway:
• The citric acid cycle, also called the tricarboxylic acid
(TCA) or Krebs cycle.
• Electron transport chain and phosphorylation, together
called oxidative phosphorylation.
• Four principal compounds participating in the
common catabolic pathway are:
• AMP, ADP, and ATP
• NAD+/NADH
• FAD/FADH2
• coenzyme A; abbreviated CoA or CoA-SH

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27-8
27Adenosine Triphosphate
• ATP is the most important compound involved in
the transfer of phosphate groups.
• ATP contains two phosphoric anhydride bonds and one
phosphoric ester bond.
ph os phoric NH2
ester N aden ine
O O O N
- N
O-P-O-P-O-P-O-CH2 O N
O- O- O- H H -N -glycos idic b on d
ph os phoric H H
anh yd rides HO OH -D-ribofuranose

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27Adenosine Triphosphate
• Hydrolysis of the terminal phosphate (anhydride) of
ATP gives ADP, phosphate ion, and energy.
O O O
- -
O-P-O-P-O-AMP + H2 O O-P-O-AMP + H2 PO4 - + 7.3 kcal/mol
-
O O- -
O
ATP AD P

• Hydrolysis of a phosphoric anhydride liberates more

energy than hydrolysis of a phosphoric ester.
• We say that ATP and ADP contain two high-energy
phosphoric anhydride bonds.
• ATP is a universal carrier of phosphate groups.
• ATP is also a common currency for the storage and
transfer of energy.
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27NAD+/NADH2
• Nicotinamide adenine dinucleotide (NAD+) is a
biological oxidizing agent.
The p lus sign on N A D +
represents th e positive O N icotinamide;
ch arge on this n itrogen CNH2 derived
O from niacin
- N+
O-P-O-CH2 O
O H H a -N-glycosidic
AMP H H bond
HO OH

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27-11
27NAD+/NADH
• NAD+ is a two-electron oxidizing agent, and is reduced
to NADH.
• NADH is a two-electron reducing agent, and is oxidized
to NAD+.
H O H H O
C C
NH2 + H+ + 2 e- NH2

:
N N
Ad Ad
NAD+ N AD H
(oxidized form) (reduced form)

• NADH is an electron and hydrogen ion transporting

molecule.

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27FAD/FADH2
• Flavin adenine dinucleotide (FAD) is also a
biological oxidizing agent.
O
H3 C N H
N Flavin
H3 C N N O
Riboflavin CH2
H C OH
H C OH Ribitol
H C OH
CH2
O
O=P-O-AMP
O-
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27FAD/FADH2
• FAD is a two-electron oxidizing agent, and is reduced
to FADH2.
• FADH2 is a two-electron reducing agent, and is oxidized
to FAD.
O H O
H3 C N H3 C N
NH NH
+ 2 H+ + 2 e -
H3 C N N O H3 C N N O
Ad Ad H
FAD FAD H2

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27Coenzyme A
• Coenzyme A (CoA) is an acetyl-carrying group.
• Like NAD+ and FAD, coenzyme A contains a unit of ADP
• CoA is often written CoA-SH to emphasize the fact that
it contains a sulfhydryl group.
• The vitamin part of coenzyme A is pantothenic acid.
• The acetyl group of acetyl CoA is bound as a high-
energy thioester.

O
CH3 -C-S-CoA
Acetyl coenzyme A
(An acyl CoA )

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27Coenzyme A
• Figure 27.7 The structure of coenzyme A.

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27Citric Acid Cycle
• Overview: the two carbon acetyl group of acetyl CoA is
fed into the cycle and two CO2 are given off.
• There are four oxidation steps in the cycle.
Acetyl -CoA CoA

H + + N AD H

N AD + Citric
N AD +
acid
cycle
(8 s teps) N AD H + H +
FAD H2 CoA CO 2
FAD N AD +
N AD H + H +
GTP
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GDP CO 2
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27-17
27Citric Acid Cycle
• Step 1: condensation of acetyl CoA with
oxaloacetate:
• The high-energy thioester of acetyl CoA is hydrolyzed.
• This hydrolysis provides the energy to drive Step 1.
O
CH3 C-SCoA
Acetyl-CoA citrate CH2 -COO-
s yn th ase
+ HO C-COO- + CoA-SH
-
CH2 -COO- Coenzyme A
O C-COO
CH2 -COO- Citrate
Oxaloacetate
• Citrate synthase, an allosteric enzyme, is inhibited by
NADH, ATP, and succinyl-CoA.
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27Citric Acid Cycle
• Step 2: dehydration and rehydration, catalyzed by
aconitase, gives isocitrate.
CH2 -COO - CH2 -COO - CH2 -COO -
- H2 O H2 O
HO C-COO - C-COO - H C-COO -
Aconitas e
CH2 -COO - CH- COO - HO CH- COO -
Citrate Aconitate Is ocitrate
• Citrate and aconitate are achiral; neither has a
stereocenter.
• Isocitrate is chiral; it has 2 stereocenters and 4
stereoisomers are possible.
• Only one of the 4 possible stereoisomers is formed in
the cycle.
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27Citric Acid Cycle
• Step 3: oxidation of isocitrate followed by
decarboxylation gives a-ketoglutarate.
CH2 -COO - N AD + N AD H + H+
H C-COO -
isocitrate
HO CH- COO - dehydrogenase
Is ocitrate
CH2 -COO - CO 2 CH2 -COO -
H C-COO - H C-H
O C-COO - O C-COO -
Oxalos uccinate a-Ketoglutarate

• Isocitrate dehydrogenase is an allosteric enzyme; it is

inhibited by ATP and NADH, and activated by ADP and
NAD+.
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27Citric Acid Cycle
• Step 4: oxidative decarboxylation of a-
ketoglutarate to succinyl-CoA.
CoA -SH
CH2 -COO - N AD + N AD H CH2 -COO -
CH2 CH2 + CO 2
-
a-ketoglutarate
O C-COO dehydrogenas e O C SCoA
a-Ketoglutarate complex Succinyl-CoA

• The two carbons of the acetyl group of acetyl CoA are

still present in succinyl CoA.
• This multienzyme complex is inhibited by ATP, NADH,
and succinyl CoA; it is activated by ADP and NAD+.
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27Citric Acid Cycle
• Step 5: formation of succinate.
CH2 -COO- succi nyl -Co A
-
+ GDP + Pi sy nth etase CH2 -COO + GTP + CoA-SH
CH2
O C SCoA CH2 -COO-
Su cci ny l-Co A Su cci nate

• The two CH2-COO- groups of succinate are now

equivalent.
• This is the first, and only, energy-yielding step of the
cycle; a molecule of GTP is produced.

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27Citric Acid Cycle
• Step 6: oxidation of succinate to fumarate.
FAD FADH2 H COO-
CH2 -COO - C
CH2 -COO - succinate - C
OOC H
dehydrogenase
Succinate Fumarate

• Step 7: hydration of fumarate to L-malate.

H COO-
C H2 O HO CH- COO -
- C fumarase CH2 -COO -
OOC H
Fumarate L-Malate

• Malate is chiral and can exist as a pair of enantiomers;

It is produced in the cycle as a single stereoisomer.
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27Citric Acid Cycle
• Step 8: oxidation of malate.
HO CH- COO - N AD + N AD H O C-COO
-

CH2 -COO - CH2 -COO -

malate
L-Malate dehydrogenase Oxaloacetate
• Oxaloacetate now can react with acetyl CoA to start
another round of the cycle by repeating Step 1.
• The overall reaction of the cycle is:
O
CH3 C-SCo A + GDP + Pi + 3 NAD + + FAD + 2 H2 O

2 CO 2 + CoA + GT P + 3 NADH + FADH2 + 3 H+

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27Citric Acid Cycle
• Control of the cycle:
• Controlled by three feedback mechanisms.
• Citrate synthase: inhibited by ATP, NADH, and succinyl
CoA; also product inhibition by citrate.
• Isocitrate dehydrogenase: activated by ADP and NAD+,
inhibited by ATP and NADH.
• a-Ketoglutarate dehydrogenase complex: inhibited by
ATP, NADH, and succinyl CoA; activated by ADP and
NAD+.

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27TCA Cycle in Catabolism
• The catabolism of proteins, carbohydrates, and
fatty acids all feed into the citric acid cycle at one
or more points:
Proteins Carbohydrates Fatty Acids

Pyruvate

Acetyl-CoA

Oxaloacetate
a-Ketoglutarate intermediates
Succinyl-CoA of the citric
Fumarate acid cycle
Malate
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27Oxidative Phosphorylation
• Carried out by four closely related multisubunit
membrane-bound complexes and two electron
carriers, coenzyme Q and cytochrome c.
• In a series of oxidation-reduction reactions, electrons
from FADH2 and NADH are transferred from one
complex to the next until they reach O2.
• O2 is reduced to H2O.
O2 + 4H+ + 4e- 2H2 O + energy

• As a result of electron transport, protons are pumped

across the inner membrane to the intermembrane
space.
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27Oxidative Phosphorylation
• Figure 27.10 Schematic diagram of the electron
transport chain and subsequent phosphorylation.

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27Complex I
• The sequence starts with Complex I.
• This large complex contains some 40 subunits, among
them are a flavoprotein, several iron-sulfur (FeS)
clusters, and coenzyme Q (CoQ, ubiquinone).
• Complex I oxidizes NADH to NAD+.
• The oxidizing agent is CoQ, which is reduced to CoQH2.

NADH + H+ + CoQ NAD+ + CoQH2 + energy

• Some of the energy released in the oxidation of NAD+ is

used to move 2H+ from the matrix into the
intermembrane space.

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27Complex II
• Complex II oxidizes FADH2 to FAD.
• The oxidizing agent is CoQ, which is reduced to CoQH2.
FADH2 + CoQ FAD + CoQH2 + energy
• The energy released in this reaction is not sufficient to
pump protons across the membrane.

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27Complex III
• Complex III delivers electrons from CoQH2 to
cytochrome c (Cyt c).
CoQH2 + 2Cyt c (reduced)

CoQ + 2 H+ + 2Cyt c (oxidized)

• This integral membrane complex contains 11 subunits,

including cytochrome b, cytochrome c1, and FeS
clusters.
• Complex III has two channels through which the two H+
from each CoQH2 oxidized are pumped from the matrix
into the intermembrane space.

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27Complex IV
• Complex IV is also known as cytochrome oxidase.
• It contains 13 subunits, one of which is cytochrome a3
• electrons flow from Cyt c (oxidized) in Complex III to
Cyt a3 in Complex IV.
• From Cyt a3 electrons are transferred to O2.
O2 + 4H+ + 4e- 2H2 O + energy
• During this redox reaction, H+ are pumped from the
matrix into the intermembrane space.
• Summing the reactions of Complexes I - IV, six H+
are pumped out per NADH and four H+ per FADH2.

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27Coupling of Ox and Phos
• To explain how electron and H+ transport produce
the chemical energy of ATP, Peter Mitchell
proposed the chemiosmotic theory:
• The energy-releasing oxidations give rise to proton
pumping and a pH gradient is created across the inner
mitochondrial membrane.
• There is a higher concentration of H+ in the
intermembrane space than inside the mitochondria.
• This proton gradient provides the driving force to
propel protons back into the mitochondrion through
the enzyme complex called proton translocating
ATPase.

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27Coupling of Ox and Phos
• Protons flow back into the matrix through channels in
the F0 unit of ATP synthase.
• The flow of protons is accompanied by formation of
ATP in the F1 unit of ATP synthase.

ADP + Pi ATP + H2O

• The functions of oxygen are:

• To oxidize NADH to NAD+ and FADH2 to FAD so that
these molecules can return to participate in the citric
acid cycle.
• Provide energy for the conversion of ADP to ATP.

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27Coupling of Ox and Phos
• The overall reactions of oxidative
phosphorylation are:
NADH + 3ADP + 12 O2 + 3Pi + H+ NAD+ + 3ATP + H2 O

FADH2 + 2ADP + 12 O2 + 2Pi FAD + 2ATP + H2 O

• Oxidation of each NADH gives 3ATP.

• Oxidation of each FADH2 gives 2 ATP.

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27The Energy Yield
• A portion of the energy released during electron
transport is now built into ATP.
• For each two-carbon acetyl unit entering the citric acid
cycle, we get three NADH and one FADH2.
• For each NADH oxidized to NAD+, we get three ATP.
• For each FADH2 oxidized to FAD, we get two ATP.
• Thus, the yield of ATP per two-carbon acetyl group
oxidized to CO2 is:
3 ATP
3 NADH x = 9 ATP
NADH
2 ATP
1 FADH2 x = 2 ATP
FADH2
1 GTP = 1 ATP
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27-36
27Other Energy Forms
• The chemical energy of ATP is converted by the
body to several other forms of energy:
• Electrical energy
• The body maintains a K+ concentration gradient across
cell membranes; higher inside and lower outside.
• It also maintains a Na+ concentration gradient across
cell membranes; lower inside, higher outside.
• This pumping requires energy, which is supplied by the
hydrolysis of ATP to ADP.
• Thus, the chemical energy of ATP is transformed into
electrical energy, which operates in neurotransmission.

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27Other Forms of Energy
• Mechanical energy
• ATP drives the alternating association and dissociation
of actin and myosin and, consequently, the contraction
and relaxation of muscle tissue.
• Heat energy
• Hydrolysis of ATP to ADP yields 7.3 kcal/mol.
• Some of this energy is released as heat to maintain
body temperature.

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27Bioenergetics
Acetyl -CoA CoA

H + + N AD H

N AD + Citric
N AD +
acid
cycle
(8 s teps) N AD H + H +
FAD H2 CoA CO 2
FAD N AD +
N AD H + H +
End GTP
GDP CO 2

Chapter 27
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