Cellular Respiration
 To
get a better understanding of how
cellular respiration takes place in our
bodies at a cellular level please take the
time to watch the following videos!

http://www.youtube.com/watch?v=00jbG_cfGuQ

http://www.khanacademy.org/science/biology/cellula
r-respiration/v/introduction-to-cellular-respiration
 Process
that extracts energy from food
(mainly glucose, but also proteins and
lipids) in the presence of oxygen –obligate
aerobes
 The
energy that is extracted is used to
synthesize ATP
 ATP
is used to supply energy directly to
cells to drive chemical reactions
 Divided
1.
2.
3.
4.
into 4 stages
Glycolysis
Pyruvate oxidation
Citric acid cycle
Electron transport and oxidative
phosphorylation
Each Stage involves the
transfer of FREE ENERGY
ATP is produced in two
different ways


•
•
Substrate-level phosphorylation
Oxidative phosphorylation
 Location
Stage
of each
• Glycolysis
 Cytosol
• Pyruvate Oxidation
 Mitochondiron
• Citic Acid Cycle
 Mitochondrion
• Electron Transport
 Mitochondrion
 Primitive
• Process found in almost all organisms
 Both prokaryotes and eukaryotes
This process is for
 Does not require O₂
the conversion of
only ONE glucose
 Involves
molecule!!!
• Soluble enzymes
 10 sequential enzyme-catalyzed reactions
• Oxidation of a 6-carbon sugar glucose
 Produces
• 2 molecules of pyruvate (3-carbon molecule)
• 2 ATP and 2 NADH
 Two Phases in which this occurs
• Initial energy investment phase
• Energy payoff phase
 Step
1
• Glucose receives a phosphate
group from ATP
• Produces glucose-6-phosphate
 Enzyme
used
• hexokinase
 Step
2
• Glucose-6-phosphate is
rearranged into its isomer
• Produces fuctose-6-phosphate
 Enzyme
used
• Phospho-glucomutase
 Recall
Isomers
• Same molecular formula but
different structure
 Step
3
• Fructose-6-phosphate receives
another phosphate group from ATP
• Produces fructose-1,6-bisphosphate
 Enzyme
Used
• Phospho-fructokinase
 Step
4
• Fructose-1,6-bisphosphate is
split
• Produces
 Glyceraldehyde-3-phosphate
(G3P)
 Dihydroxyacetone phosphate
(DHAP)
 Enzyme
used
• aldolase
 Step
5
• Dihydroxyacetone (DHAP) is
converted
• Produces
 glyceraldehyde-3-phosphate (G3P)
 Enzyme
used
• Triosephosphate-isomerase
 This
is the last step of the
initial energy investment
phase
• Total of 2 ATP invested
• End result is 2 G3P molecules
Because there are now 2
molecules of G3P at the
end of the initial energy
investment phase, all the
reactions in the energy
payoff phase (6 to 10) are
DOUBLED!!
 Step
6
• 2 electrons and 2 protons are
removed from G3P
• NAD⁺ accepts both electrons and a
proton (becoming NADH)
• Other proton is released into cytosol
• Phosphate group is attached
• Produces
 Two 1,3-bisphosphoglycerate
 Enzyme
used
• Triosephosphate-dehydrogenase
 Step 7
• A phosphate group from
1,3-bisphosphoglycerate is
transferred to ADP
• Produces
• 2 ATP
• Two 3-phosphoglycerate
 Enzyme used
• Phosphoglycerate kinase
 ATP is produced by
• Substrate-level phosphorylation
 Step 8
• 3-phosphoglycerate is rearranged
• Phosphate group is shifted from 3-
carbon to 2-carbon
• Produces
 Two 2-phosphoglycerate
 This
process is done via mutase
reaction
• Shifting of a chemical group to
another within the same molecule
 Enzyme used
• phosphoglucomutase
 Step
9
• Electrons are removed from one part
of 2-phosphoglycerate and delivered
to another part of the molecule
• Produces
 Two H₂O molecules
 Two Phosphoenolpyruvate
 Enzyme
• Enolase
used
 Step
10
• Final phosphate group is
transferred from
phosphoenolpyruvate (PEP) to ADP
• Produces
 2 ATP
 Two Pyruvate molecules
 Enzyme
used
• Pyruvate kinase
 ATP
is produced by
• Substrate-level phosphorylation
Phosphate groups are
attached to ADP from a
substrate forming ATP
(enzyme catalyzed
reaction)
 ALL ATP molecules are
produced this way in
Glycolysis

 Initial energy investment
• 2 ATP are consumed
phase
 Energy payoff phase
• 4 ATP produced
• 2 NADH molecules are synthesized
Overall NET reaction;
Glucose + 2 ADP + 2 Pi + 2 NAD⁺ → 2 pyruvate + 2 ATP + 2 NADH + 2H⁺


62 kJ of energy is stored by the synthesis of 2 ATP molecules
Rest of the free energy is stored in the 2 pyruvate molecules
 Remember
glycolysis occurs in the cytosol of the cell
 The
Citric Acid Cycle (next step) occurs in the
mitochondrial matrix
 Pyruvate
must pass through the inner and outer
membrane of the mitochondrion
 Multi-step
process
• Outer membrane
 Pyruvate diffuses across the outer membrane through
large pores of mitochondrion
• Inner membrane
 Pyruvate-specific membrane carrier is required
• Inside Matrix
 Pyruvate is converted into an acetyl group
 Acetyl group is bonded to coenzyme A
 Produces an acetyl-CoA complex
Conversion of pyruvate to acetyl-CoA
Involves 2 Reactions
1. Decarboxylation reaction
 Carboxyl group (-COO⁻) of pyruvate is removed
 Produces
 CO₂
2. Dehydrogenation reaction
 2 electrons and a proton are transferred
 Produces
 NADH
 H⁺ in solution
Net reaction
2 pyruvate + 2 NAD⁺ + 2 CoA → 2 acetyl-CoA + 2 NADH + 2 H⁺ + 2 CO₂
 Acetyl
group reacts with the sulfur atom
of coenzyme A
 Acetyl-CoA is the molecule that will start
the Citric Acid Cycle
 Discovered
by
• Sir Hans Krebs
(1900-1981)
• Consists of 8 enzyme
catalyzed reaction
• ALL ATP are produced
by substrate-level
phosphorylation
 Step
1
• 2-carbon acetyl group carried by
coenzyme A is transferred to
oxaloacetate
• Produces
 Citrate
 Enzyme
used
• Citrate synthase
 Step
2
• Citrate is rearranged into its
isomer
• Produces
 Isocitrate
 Enzyme
used
• Aconitase
 Step
3
• Isocitrate is oxidized
• Produces
 α-ketoglutarate
 NADH
 CO₂
 H⁺
 Enzyme
used
• Isocitrate
dehydrogenase
 Step
4
• α-ketoglutarate is oxidized
• Produces
 Succinyl CoA
 CO₂
 NADH
 Enzyme
used
• α-ketoglutarate
dehydrogenase
 Step
5
• CoA is released from succinyl
CoA
• Produces
 Succinate
 Energy released converts GDP to
GTP which couples production of
ATP
 Enzyme
used
• Succinyl CoA synthetase
 GTP
• Activates substrate to produce
ATP
 Step
6
• Succinate is oxidized
• Produces
 Fumarate
 FADH₂
 Enzyme
used
• Succinate dehydrogenase
 FADH₂
• Nucleotide-based molecule
• Electron carrier
 Step
7
• Fumarate is converted with the
addition of H₂O
• Produces
 Malate
 Enzyme
used
• Fumarase
 Step
8
• Malate is oxidized
• Produces
 Oxaloacetate
 NADH
 H⁺
 Enzyme
used
• Malate dehydrogenase
2
molecules of pyruvate are converted to Acetyl-CoA
 Citric Acid Cycle goes through two turns for every
single glucose molecule that is oxidized
1 Turn:
Acetyl-CoA + 3 NAD⁺ + FAD + ADP + Pi →
2 CO₂ + 3 NADH + 3 H⁺ + FADH₂ + ATP + CoA
ATP is synthesized by substrate level phosphorylation coupled by
GTP
 ALL
of the carbon atoms that make up a
glucose molecule are converted into CO₂
• oxidation of pyruvate
• acetyl groups
Total # of NET Molecules Produced
NADH
FADH₂
CO₂
ATP
Glycolysis 2
0
0
2
Pyruvate 2
Oxidation
0
2
0
Citric
Acid
Cycle
2
4
2
6
 Process
that extracts potential energy that
is stored in NADH and FADH₂
• These molecules were formed during
glycolysis, pyruvate oxidation, and citric acid
cycle
This
energy is used to synthesize
additional ATP (A lot more)
 Occurs
on the inner mitochondrial
membrane
 Facilitates the transfer of electrons from
NADH and FADH₂ to O₂
 Composed
of
• 4 Complexes
 Complex I, NADH dehydrogenase
 Complex II, succinate dehydrogenase
 Complex III, cytochrome complex
 Complex IV, cytochrome oxidase
• 2 Electron shuttles
 Ubiquinone (UQ)
 Hydrophobic molecule – shuttles electrons from complex I and II to
complex III
 Cytochrome C (cyt c)
 Shuttles electrons from complex III to complex IV
 Complexes
I, III, IV
•Each has a cofactor
 Each cofactor has increasing electronegativity
 Alternate between reduced and oxidized states
 Electrons move towards more electronegative
molecules (downstream)
 Final electron acceptor – OXYGEN (most
electronegative)
 Pulls electrons from complex IV
Final
electron acceptor
• Removes two electrons from complex IV
• Reacts with 2 H⁺ to produce H₂O
 BUT
So
WE BREATH IN O₂ NOT A SINGLE O
for every O₂ molecule
• Pulls a total of 4 electrons through the electron
transport chain
• 2 H₂O molecules are produced
 Pulling
4 electrons from complex IV triggers
a chain reaction between other complexes!!
 Starts
with O₂
 Pulls electrons through
the chain of complexes
 NADH is least
electronegative but
contains most free
energy
 O₂ has highest
electronegativity but
contains least amount of
free energy
 Electron
Transport from NADH or FADH₂ to
O₂ does not produce any ATP!!
 What does?
 Proton Gradient
• Transport of H⁺ ions across the inner mitochondrial
membrane from the matrix into the inter-membrane
space
 Creates
 Proton-Motive
Force
• Chemical gradient (difference in concentrations)
• Electro potential gradient is created (because of the
positive charge on Hydrogen atom)
 The
ability of cells to use the protonmotive force to do work
 Synthesizes ATP using electrochemical
gradient
 Uses ATP synthase enzyme
• ATP is synthesized using oxidative
phosphorylation
 Relies
on ATP synthase
• Forms a channel which H⁺ ions can pass freely
• H⁺ ions cause the synthase to rotate harnessing
potential energy to synthesize ATP