CHAPTER 27

Bioenergetics; How the

Body
Converts Food to Energy
 Metabolism
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 process of breaking down large
nutrient molecules into smaller molecules with
the concurrent production of energy.
• Anabolism: The process of synthesizing larger
molecules from smaller ones.

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METABOLISM is the sum of catabolism and
anabolism.

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Figure 27-1 Simplified
schematic diagram of the
common metabolic
pathway, an imaginary
funnel representing what
happens in the cell.

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 Cells 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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Figure 27-2
Diagram of a
rat liver cell, a
typical higher
animal cell.

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• Figure 27-3 Schematic of a mitochondrion cut to
reveal the internal organization.

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 The Common Metabolic
Pathway
The two parts to the common catabolic pathway:
• The citric acid cycle, also called the tricarboxylic acid cycle (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: agents for the storage and transfer of
phosphate groups.
• NAD+/NADH: agents for the transfer of electrons in biological
oxidation-reduction reactions.
• FAD/FADH2: agents for the transfer of electrons in biological
oxidation-reduction reactions.
• Coenzyme A; abbreviated CoA or CoA-SH: An agent for the
transfer
of acetyl groups. 8
 Adenosine Triphosphate (ATP)
ATP is the most important compound involved in
the transfer of phosphate groups.
• ATP contains two phosphoric anhydride bonds and
one phosphoric ester bond.

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 Adenosine Triphosphate (ATP)
• Hydrolysis of the terminal phosphate (anhydride) of ATP gives
ADP, dihydrogen phosphate ion, and energy.

• Hydrolysis of a phosphoric anhydride liberates more energy than

the hydrolysis of a phosphoric ester.
• We say that ATP and ADP each contain 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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 NAD+/NADH
• Nicotinamide adenine dinucleotide (NAD+) is a
biological oxidizing agent.
The plus sign on NAD+
represents the positive O Nicotinamide;
charge on this nitrogen CNH2 derived
O from niacin
-
O-P-O-CH2 N+
O
O H H a b-N-glycosidic
AMP H H bond
HO OH

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 NAD+/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+. The structures shown here are the nicotinamide
portions of NAD+ and NADH.

• NADH is an electron and hydrogen ion transporting

molecule.
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 FAD/FADH2
• Flavin adenine dinucleotide (FAD) is also a
biological oxidizing agent.
O
H3C N H
N Flavin
H3C N N O
Riboflavin CH2
H C OH
H C OH Ribitol
H C OH
CH2
O
O=P-O-AMP
O- 13
 FAD/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.
• Only the flavin moiety is shown in the structures
below.

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 Coenzyme A
Coenzyme A (CoA) is an acetyl group carrier.
• 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.

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 Coenzyme A
• Figure 27-7 The structure of coenzyme A The business
end is the -SH (sulfhydryl) group at the left end.

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 Citric Acid Cycle
A simplified view of the citric acid cycle showing only the
carbon balance. The fuel is the two-carbon acetyl group of
acetyl CoA. With each turn of the cycle two carbons are
released as CO2.

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 Citric Acid Cycle
Step 1: The condensation of acetyl CoA with
oxaloacetate:
• The high-energy thioester of acetyl CoA is
hydrolyzed.
• This hydrolysis provides the energy to drive
Step 1.
• Citrate synthase, an allosteric enzyme, is
inhibited by NADH, ATP, and succinyl-CoA.

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 Citric Acid Cycle
Step 2: Dehydration and rehydration, catalyzed by
aconitase, gives isocitrate.
• 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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 Citric Acid Cycle
Step 3: Oxidation of isocitrate to oxalosuccinate
followed by decarboxylation gives a-ketoglutarate.
CH2-COO- NAD+ NADH + H+
H C-COO-
isocitrate
-
HO CH-COO dehydrogenase
Isocitrate
CH2-COO
- CO2 CH2-COO-
H C-COO- H C-H
O C-COO- O C-COO-
Oxalosuccinate a-Ketoglutarate

• Isocitrate dehydrogenase is an allosteric enzyme; it is

inhibited by ATP and NADH, and activated by ADP and
NAD+. 20
 Citric Acid Cycle
Step 4: Oxidative decarboxylation of a-ketoglutarate to
succinyl-CoA.
CoA-SH
- +
CH2 -COO NAD NADH CH2 -COO
-

CH2 CH2 + CO2

a-ketoglutarate
O C-COO- O C SCoA
dehydrogenase
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+.
21
 Citric Acid Cycle
• Step 5: Formation of succinate.
-
CH2-COO succinyl-CoA
CH -
CH2 + GDP + Pi synthetase 2
- + GTP + CoA-SH
COO
-

O C CH2-COO
SCoA

Succinyl-CoA Succinate

• 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.
22
 Citric Acid Cycle
• Step 6: Oxidation of succinate to fumarate.

• Step 7: Hydration of fumarate to 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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 Citric Acid Cycle
• Step 8: Oxidation of malate.

• 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:

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 Citric 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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 TCA Cycle in Catabolism
The catabolism of proteins, carbohydrates, and
fatty acids all feed into the citric acid cycle at one
or more points:

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 Oxidative 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.

• As a result of electron transport, protons are pumped across

the inner membrane to the intermembrane space.

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 Oxidative Phosphorylation
• Figure 27-10 Schematic diagram of the electron
and H+ transport chain and subsequent
phosphorylation.

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 Complex 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.

• Some of the energy released in the oxidation of NADH is

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

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 Complex II
• Complex II oxidizes FADH2 to FAD.
• The oxidizing agent is CoQ, which is reduced to
CoQH2.

• The energy released in this reaction is not

sufficient to pump protons across the
membrane.
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Complex III
• Complex III delivers electrons from CoQH2 to
cytochrome c (Cyt c).

• 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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 Complex 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.

• 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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 Chemiosmotic Pump
To explain how electron and H+ transport produce the chemical
energy of ATP, Peter Mitchell proposed the chemiosmotic theory
that electron transport is accompanied by an accumulation of
protons in the intermembrane space of the mitochondrion, which in
turn
creates osmotic pressure; the protons driven back to the
mitochondrion under this pressure generate ATP.
• 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. 33
 Chemiosmotic Pump
• 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.

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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 Chemiosmotic Pump
• The overall reactions of oxidative phosphorylation
are:

• Oxidation of each NADH gives 3ATP.

• Oxidation of each FADH2 gives 2 ATP.
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 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:

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Other Forms of Energy
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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 Other 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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 Other Forms of Energy
Figure 27-11 Schematic diagram of muscle
contraction.

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Chapter 27 Bioenergetics

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