Aerobic 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
Why Make ATP?
• Referred to as energy currency of the cell
• Provide energy for chemical reactions to take place
in our body (cells)
Mitochondria
• Site of cellular respiration (where ATP is made)
• Conists of
– Outer membrane
– Inner membrane
– Matrix
– Cristae
Aerobic Cellular Respiration
• Divided into 4 stages
1.
2.
3.
4.
Glycolysis
Pyruvate oxidation
Citric acid cycle
Electron transport chain and
oxidative phosphorylation
• Each Stage involves the
transfer of FREE ENERGY
• ATP is produced in two
different ways
– Substrate-level phosphorylation
– Oxidative phosphorylation
Aerobic Respiration
• Location of each
Stage
• Glycolysis
– Cytosol
• Pyruvate Oxidation
– Mitochondrial matrix
• Citric Acid Cycle
– Mitochondrial matrix
• Electron Transport
– Inner mitochondrial
membrane
Glycolysis
• Primitive
This process is for the conversion of only
ONE glucose molecule!!!
– Process found in almost all
organisms
– Both prokaryotes and eukaryotes
• Does not require O₂
• Involves
– Soluble enzymes
(10 sequential enzyme-catalyzed
reactions)
– Oxidation of a 6-carbon sugar
glucose
• Produces
– 2 molecules of pyruvate
(3-carbon molecule)
– 4 ATP and 2 NADH
• Two Phases in which this occurs
– Initial energy investment phase
– Energy payoff phase
Glycolysis Overview
Glycolysis Overview
• Initial energy investment
phase
– 2 ATP are consumed
• 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
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
Pyruvate
• Pyruvate can take 2 paths
from this point:
1. Aerobic Respiration
(with oxygen)
– Pyruvate moves into
mitochondria and ATP is
made via Krebs Cycle and
Electron Transport Chain
2. Anaerobic Respiration
(without oxygen)
–
Pyruvate stays in
cytoplasm and is
converted into lactic acid -Lactic Acid Fermentation
Pyruvate Oxididation
• 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
Pyruvate Oxidation
• 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
Pyruvate Oxidation
Conversion of pyruvate to acetyl-CoA
Involves 2 Reactions
• Catalyzed by pyruvate dehydrogenase
• Decarboxylation reaction
– Carboxyl group (-COO⁻) of pyruvate is removed
– Produces
• CO₂
• 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
Pyruvate Oxidation
• Acetyl
group
reacts with
the sulfur
atom of
coenzyme A
• Acetyl-CoA
is the
molecule
that will
start the
Citric Acid
Cycle
Citric Acid Cycle
• Discovered by
– Sir Hans Krebs
(1900-1981)
– Consists of 8
enzyme catalyzed
reaction
– ALL ATP are
produced by
substrate-level
phosphorylation
Citric Acid Cycle Overview
• 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
Citric Acid Cycle Overview
Citric Acid Cycle
• ALL of the carbon atoms that make up a glucose
molecule are converted into CO₂
– oxidation of pyruvate
– acetyl groups
Oxidation of ONE Glucose Molecule
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
Electron Transport Chain (Chemiosmosis)
• Process that extracts potential energy that is stored in
NADH and FADH₂
– These molecules were formed during glycolysis, pyruvate
oxidation, and citric acid cycle
– Redox reactions – transfer of electrons
• This energy is used to synthesize additional ATP
(A lot more) via oxidative phosphorylation
The Electron Transport Chain
• Occurs on the inner mitochondrial membrane
• Facilitates the transfer of electrons from NADH and
FADH₂ to O₂
The Electron Transport Chain
• 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
The Driving Force Behind Electron Transport
• 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
How a Single Oxygen Atom Works (O)
• Final electron acceptor
– Removes two electrons
from complex IV
– Reacts with 2 H⁺ to
produce H₂O
• BUT WE BREATH IN O₂
NOT A SINGLE O
• So 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!!
What happens in this chain of reactions?
• 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
Proton Gradient
• 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 intermembrane space
• Creates
• Proton-Motive Force
– Chemical gradient
(difference in
concentrations)
– Electro potential gradient
is created (because of the
positive charge on
Hydrogen atom)
Proton Gradient
Chemiosmosis
• The ability of
cells to use the
proton-motive
force to do work
• Synthesizes ATP
using
electrochemical
gradient
• Uses ATP
synthase enzyme
– ATP is
synthesized
using oxidative
phosphorylation
34 ATP are Produced!
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
NADH from Glycolysis
• NADH produced during glycolysis is in cytosol
– Transported into mitochondria via two shuttle
systems
• Malate-aspartate shuttle
• Glycerol-phosphate shuttle
NADH and FADH₂
• For every NADH that is oxidized
– About 3 ATP are synthesized
– 10 NADH x 3 ATP = 30 ATP
– NADH is derived from vitamin niacin
• For every FADH₂
• NADH and FADH₂
are involved in
REDOX reactions
• Considered
Cosubstrates
– About 2 ATP are synthesized
– 2 FADH₂ x 2 ATP = 4 ATP
– FADH₂ is derived from vitamin riboflavin (B₂)
• Total of 34 ATP synthesized by electron transport chain
Efficiency of
Cellular
Respiration
Efficiency of Cellular Respiration
•
•
•
•
38 ATP produced
Hydrolysis of ATP yields 31kJ/mol
31 kJ/mol x 38 ATP = 1178 kJ/mol
Oxidation of Glucose contains 2870 kJ/mol of
energy
(1178kJ / mol)
x100%  41%
(2870kJ / mol)
Only 41% of the energy in oxidation of
glucose in converted into ATP
The rest is lost as thermal energy
Cells that need a constant supply of ATP
• Brain cells, muscle cells
– Need burst of ATP during periods of
activity
• Creatine phosphate pathway
– Immediate source of energy
– Creatine phosphate splits (high
energy)
– Donated directly to ADP to re-form
ATP
– Stored within cell (3 to 5 times
more than ATP)
– Provides enough energy for minute
walk or short distance sprint
creatine + ATP → creatine phosphate
+ ADP
creatine phosphate → creatine + ATP
Cellular Respiration
• Regulated
– Feedback inhibition
• Enzyme used
– Phosphofructokinase
• Inhibited by
– High levels of ATP
– High levels of citrate
• Activated by
– High levels of ADP
– High levels of AMP
• Glucose
– Stored as glycogen