Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-

Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

How cells make ATP:

Energy-Releasing Pathways
Learning

BL 201
 Phosphorylation

Substrate level phosphorylation

• Direct transfer of the phosphate group with its energy

Chemiosmosis
• Energy of electrons in ETC
• pumps H+ into intermembrane space
• Protons (H+) accumulate in
intermembrane space
- oxidative phosphorylation
- photophosphrylation
Proton Gradient
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Metabolism 2 Complementary
Components

1. Catabolism
• Splits or breaks down molecular structure
Learning

• Releases energy: exergonic

2. Anabolism
• Synthesizes or builds up molecular
structure,
• Requires energy: endergonic
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Cellular Respiration

• Cellular respiration involves conversion

of energy in the chemical bonds of
Learning

nutrients to a different form of chemical

energy, ATP
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Types of Respiration
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• Anaerobic respiration
• Does not require oxygen
• Found in all cells
• When an organism has only anaerobic respiration, it cannot
be very complex or large: thus only unicells are strictly
Learning

anaerobic
• Fermentation
• A mechanism to recycle NADH
• Aerobic respiration
• Requires oxygen
• Uses complex membrane-bound cellular mechanisms
• In bacteria, aerobic respiration in cytoplasm and electron
transport membranes
• In eukaryotes, aerobic respiration usually involves
mitochondria
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Classes of Respiration
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Reactions
• Respiration reactions are a series of
reduction/oxidation processes
• Dehydrogenation
Learning

• 2 H+ and 2 e- are pulled from substrate to coenzyme such

as NAD+ and FAD+
• Decarboxylation
• Carboxyl is removed from a substrate to make CO2
• “Make-ready” reaction
• A molecule is rearranged to prepare it for a subsequent
dehydrogenation or decarboxylation
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Aerobic Respiration:
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A Redox Process

1 Glucose + 6 Oxygen
Learning

Reduction

Oxidation

6 Carbon Dioxide + 6 Water + 36-38 ATPs

ENERGY
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Energy Release During
Releasing Pathways

Respiration
Copyright  2002 by Harcourt College Publishers, a division of Thomson
Learning

• Energy is released from chemical sources via anaerobic or

oxidative respiration in a series of small steps.
• Slow, controlled release of the same amount of energy
allows it to be released in a much more usable form.
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-

Four Stages of Aerobic Respiration

Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Occur in Two Cellular

Compartments
[Link] the cytoplasm
• Glycolysis
Learning

2. In the mitochondrion
• Pyruvate is degraded to acetate and
combined with coenzyme A (CoA)
• The Krebs Cycle – tricarboxylic acid cycle --
citric acid cycle
• The electron transport chain (ETC) and
chemiosmotic phosphorylation
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Four stages of aerobic

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respiration
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Glycolysis: First
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Stage

• 2 stages: First
Learning

stage shown here

• Glucose is broken
1. Two ATPs
phosphorylate
glucose, which
becomes
unstable and is
broken.
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Glycolysis: Stage Two

Copyright  2002 by Harcourt College Publishers, a division of Thomson

• Further addition of
phosphate to each
Learning

3C carbohydrate
occurs by a NAD/Pi
redox reaction,
then
• All four
phosphates are
removed to add
them to ADP to
make 4 ATPs.
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-

Glycolysis in Detail
Releasing Pathways
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Stage 1: Investment of Energy

Glucose: C-C-C-C-C-C
Enzyme Process
Hexokinase ATP ADP Phosphorylate

Glucose-6-phosphate: C-C-C-C-C-C-P
Phosphoglucoisomerase Rearrange
Learning

Fructose-6-phosphate: C-C-C-C-C-C-P

Phosphofructokinase ATP ADP Phosphorylate

Fructose-1,6-bisphosphate: P-C-C-C-C-C-C-P

Aldolase Cleave

Isomerase P-C-C-C C-C-C-P Isomerise: Mass action

Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate
Not useful energetically Used in next step
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Glycolysis, Stage 2: Energy Payback
Copyright  2002 by Harcourt College Publishers, a division of Thomson

All steps here, multiply by 2

Enzyme Process
Glyceraldehyde 3-phosphate OC-C-C-P
Glyceraldehyde 3- NAD+ NADH Phosphorylation
phosphate dehydrogenase
1,3-bisphosphoglyceric acid POC-C-C-P
Learning

Phosphoglycerokinase ADP ATP Dephosphorylates C-backbone

Phosphorylates ADP
3-phosphoglyceric acid HOOC-C-C-P
Phosphoglyceromutase Isomerization
2-phosphoglyceric acid HOOC-C-P-COH
Enolase Dehydration (removes water)
2-phosphoenolpyruvic acid HOOC-C-P-C
Dephosphorylates C-backbone
Pyruvate kinase ADP ATP Phosphorylates ADP

Pyruvate: pyruvic acid HOOC-C-C

“Feeds” reactions in the mitochondrion
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

The Mitochondrion
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• The mitochondrion takes the output of glycolysis and

produces considerably more energy in the form of
ATP
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Diagram of Mitochondrion
• Outer
membrane
• Inner
Learning

membrane
• Cristae
• Matrix
• Intermembran
e space
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

The
Formation
of Acetyl-CoA
Learning

• Pyruvate is converted to
an
acetyl group by
decarboxylation
• Releases carbon dioxide
• Oxidation of the acetyl
group,
coupled with the vitamin
Coenzyme A, causes
linkage
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Citric Acid Cycle:

Copyright  2002 by Harcourt College Publishers, a division of Thomson

Overview
Learning

• Two carbons from the

acetyl group combined
with the four carbon
Oxaloacetate to make
6-
carbon citric acid
• Citric acid broken
down
twice, releasing
carbon
dioxide and NADH
• 4-carbon compound
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
(1) The unstable bond attaching the acetyl group to
coenzyme A breaks. The 2-carbon acetyl group
becomes attached to a 4-carbon oxaloacetate
Copyright  2002 by Harcourt College Publishers, a division of Thomson

(8) Malate is dehydro- molecule, forming citrate, a 6-carbon molecule with

generated, forming Glucose three carboxyl groups. Coenzyme A is free to combine
Fatty
oxaloacetate. The two with another
a 2-carbon group and repeat the process.
hydrogens removed are c
transferred to NAD+. i
Oxaloacetate can now Malate
d
combine with another dehydrogenase Oxaloacetate Citrate synthase s
molecule of acetyl
Coenzyme A
coenzyme A, beginning
a new cycle.

(2) The atoms of citrate are rearranged by two

preparation reactions in which first, a molecule of
Malate water is removed, and then a molecule of water
Citrate is added. Through these reactions citrate is
Fumarase converted to its isomer, isocitrate.
(7) With the addition Aconitase
of water, fumarate
Learning

is converted to CITRIC
malate. ACID
CYCLE

Fumarate

Isocitrare
Succinate Isocitrate dehydrogenase
dehydrogenase
(6) Succinate is
oxidized when (3) Isocitrate undergoes
two of its dehydrogenation and
hydrogens are decarboxylation to yield
transferred to the 5-carbon compound
FAD, forming -ketoglutarate.
Coenzyme A
FADH2. The
Succinate
resulting
compound is -ketoglutarate
Coenzyme A
fumarate. -ketoglutarate
Succinyl CoA dehydrogenase
synthetase
(4) Next -ketoglutarate undergoes
(5) In this step succinyl coenzyme A is converted to decarboxylation and dehydrogenation
succinate, and substrate-level phosphorylation takes to form the 4-carbon compound
Succinyl
place. The bond attaching coenzyme A to succinate (~S) succinyl coenzyme A. This reaction is
coenzyme A
is unstable. The breakdown of succinyl coenzyme A is catalyzed by a multienzyme complex
Fig. 7.07
coupled to the phosphorylation of GDP to form GTP similar to the complex that catalyzes
(a compound similar to ATP). GTP transfers its phosphate the conversion of pyruvate to acetyl
to ADP, yielding ATP. coenzyme A.
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Citric Acid
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Cycle:
First Two Steps
• Two carbons are
added to four
Learning

carbon
oxaloacetate
• This produces
citrate
• Citrate is
rearranged to
make isocitrate
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
2 CO2 Removed to Make 5C, 4C
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

• Molecule
Two NADH are produced
• Then CoA is added at the site of phosphorylation, and that
phosphate passes GDP to make GTP, then from GTP to ADP to
make ATP; final product is succinic acid (succinate)
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Rearrangements
Regenerate Oxalic
Acid
• FADH2 is generated in
the formation of
fumarate from succinate
Learning

• Then fumarate is
rearranged and
hydrogenated to malate
• Which is then oxidized to
oxaloacetate
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Glucose Catabolism
• By the end of two turns of the Krebs, or TCA
Learning

cycle, glucose is catabolized to

• 4 CO2 (other 2 CO2; in conversion step)
• 6 NADH (from TCA)
• 2 FADH2
• 2 ATP from TCA cycle and 2 ATP from
glycolysis
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Redox in the ETC

• Electron carriers experience cyclic oxidation and

reduction as electron/proton pairs pass through
the ETC
Learning

• The energy of the electrons steadily drops as they

move through the ETC
• Energy is tapped off the stream of electrons by
pumping protons into the intermembrane space
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Electron Carriers & Acceptors

• Important electron carriers are

• FMN – flavin mononucleotide
• Ubiquinone – a lipid also called coenzyme Q
Learning

(CoQ)
• Iron-sulfur proteins
• Cytochromes
• The final electron acceptor is oxygen, which
combines with hydrogen to form water
 Electron Transport
Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Complexes
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• Complex I, NADH-ubiquinone oxidoreductase

accepts electrons from NADH
[from glycolysis, formation of acetyl-CoA and the TCA.
• Complex II (succinate-ubiquinone reductase)
accepts electrons from FADH2
Learning

• Reduced ubiquinone carries electrons from Complex I

or II to Complex III: ubiquinone-cytochrome c
oxidoreductase
• Electrons from Complex III are accepted by Complex
IV – cytochrome oxidase – which is the enzyme that
combines oxygen with protons and electrons to
produce
• Water as a stable, final electron acceptor, that easily
moves away from the reaction site
 Biology, Sixth Edition
The Inner Membrane:
Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Electron Transport
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Chain
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
The Electron Transport Chain
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Pumps Protons Across the Inner

Membrane
Inner membrane
Learning

• Creates a gradient
• Proton concentration
high between the
OM and IM
• Stores energy
 Biology, Sixth Edition ATP
ChapterProduction
Releasing Pathways
by
7, How Cells Make ATP: Energy-

Chemiosmosis
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Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Respiration: Releasing Pathways

Energy
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•
Budget
Glycolysis, citric acid
cycle by themselves
produce few ATPs
• Most energy is removed
by redox reactions that
produce the electron
carriers NADH and
Learning

FADH2.
• That energy is
transferred to a proton
gradient, which is
broken down to provide
energy to produce large
quantities of ATP by
chemiosmosis
• Only 2 ATP produced per
glucose via glycolysis;
32-34 via aerobic
respiration
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

• Inner mitoch mb is not permeable to large

molecules as NADH thus e-s and not whole
molecule transferred into mitoch.

• In liver, kidney, & heart cells  special shuttle

tranfers e-s from NADH through inner mitoch mb
Learning

to NAD+ in matrix. thus produce 3 ATP/

NADH (per pair of e-s)

• In skeletal muscle, brain, + other cells

shuttle requires more E, e-s are at lower E-state
when enter inner mitoch mb and are accepted by
ubiquinone  2ATP/pair of e-s
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

The Sources of Metabolic

“Fuel” Get Into the
Respiratory Chain by
Several Avenues
Learning

• Protein
• Amino
acids
• Carbohydrat
e
• Sugars
• Fats
• Glycerol
• Fatty acids
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Regulation of
Metabolism
• Phosphofructokinase
• Early enzyme in glycolysis
Learning

• Is key control point

• Example of metabolic
homeostatic control point
• Feedback inhibition by
products of respiration
• ATP
• Citrate
• Stimulation
• AMP
• ATP metabolite
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Pyruvate ‘Feeds’ Aerobic Respiration or

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Fermentation in the Absence of Oxygen

• Pyruvate is a key metabolic molecule

• In aerobe or in high O2, goes to mitochondrion

Learning

• In anaerobe, or when O2 becomes low:

(e.g. - in heavily exercised muscle) it feeds
fermentation

• In anaerobes:
• leads to ethanol production (some bacteria, some
protists)
• leads to lactic acid production (muscle, bact, some
fungi)
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson

Fermentation
• Ethanolic fermentation
common in yeast (right)
• Allows glycolysis to
continue by recycling
NADH to NAD+
Learning
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways

Anaerobic respiration
Copyright  2002 by Harcourt College Publishers, a division of Thomson

• Does not use O2 as final e-acceptor

• Uses an inorganic substance such as nitrate (NO3-) or

sulfate (SO4-2) as final e- acceptor
Learning

• Ex: C6H12O6 + 12KNO3 6CO2 + 6H2O+12KNO2+ ATP

• Mechanism of ATP synthesis: substrate level

phosphorylation & chemiosmosis

• Bacteria that live in anaerobic conditions

(intestine,stagnant ponds…)
 Biology, Sixth Edition Chapter 7, How Cells Make ATP: Energy-
Releasing Pathways
Copyright  2002 by Harcourt College Publishers, a division of Thomson
Learning