Lecture #64

Cellular Respiration

Textbook Chapter #6
 Cellular Respiration
• Cells require energy in order to grow, reproduce,
manufacture, transport materials, move and
maintain cell structure
• All of this energy comes from the sun
• Light energy is converted into chemical energy via
the process of photosynthesis
• Some bacteria, all plants and algae do photosynthesis

• Photosynthesis uses the energy provided by the

sun to rearrange bonds between CO2 and H2O in
order to form glucose and O2

• Cellular Respiration breaks down glucose and O2

produced by photosynthesis, producing CO2 and H2O
• It also stores the chemical energy that is released in the
bonds of ATP
• Some of the energy is lost as heat during the
various conversions
 Breathing Provides the Oxygen
Needed for Cellular Respiration
• Respiration is defined as an exchange of gases
• Organisms obtain O2 from their environment and release CO2 as waste
• Respiration may also be described as the aerobic harvesting of energy
from food molecules by cells
• Distinguishes cellular respiration from breathing

• Breathing and Cellular Respiration are tightly connected

• When the runner breathes in air, O2 that is taken up enters
into the blood stream traveling to all body cells
• The muscles cells actively involved in running take up the O2
which is used in the mitochondria of the muscle cells
• In the mitochondria energy from glucose and other organic
molecules in conjunction with the O2 is harvested in order to
generate ATP via cellular respiration
• This provides the energy for the muscular contraction
• CO2 is expelled from the lungs as a waste product
 Cellular Respiration uses ATP for
Energy Storage
• Cellular respiration ultimately function to generate ATP for cellular
work
• Glucose is used as an example however there are a number of other organic
molecules that can be used to generate ATP
• Bonds between atoms in glucose and oxygen break and reform as CO2 and H2O
releasing energy that is then stored in the bonds of ATP

• Cellular respiration may produce as many as 32 ATP molecules per one

glucose molecule
• This 32 ATP only represents ~40% of the total energy available per glucose
molecule
• The remaining energy is lost as heat
 Bodily Activity that Uses ATP
• In order to breathe, maintain a heart beat and maintain body
temperature at 37oC the body requires a constant supply of energy
• The most energy required by the body each day is for the brain

• Brain cells burn ~120 grams of glucose each day and use 15% of the bodies
total oxygen consumption

• In order to maintain life and carry out necessary bodily functions,

approximately 75% of the total energy taken in each day is utilized by the body

• Voluntary activities are also powered by

cellular respiration
How Exactly is Energy Harvested from
Glucose
• Chemical bonds that hold a molecule together result from shared
electrons
• These shared electrons contain the energy that is available to the cell

• These electrons are transferred to O2 as C-H bonds in glucose are

broken and the H-O bonds in water are formed during cellular
respiration
• O2 attracts these electrons very strongly and as the
electrons fall down a ‘staircase’ from the bonds of glucose
to O2 lots of energy is released which is then stored in the
chemical bonds of ATP

• Glucose looses hydrogen atoms as it is converted

to CO2
• O2 gains hydrogen atoms as it is converted into water
• Hydrogen transfers represent electron transfers because each hydrogen
consists of 1 H+ and 1 e-
 How Exactly is Energy Harvested from
Glucose
• When electrons are moved from one molecule to another the reaction
is called a redox reaction or an oxidation-reduction reaction
• The loss of electrons from one molecule is called oxidation
• An atom that has lost electrons is referred to as having been oxidized

• The gain of electrons by another molecule is called reduction

• An atom that has gained electrons is referred to as having been reduced

• A transfer of electrons always requires a donor and a recipient, therefore

oxidation and reduction reactions always occur together

• Overall result of cellular respiration: glucose looses electrons as H atoms and

becomes oxidized and O2 gains electrons in the form of H atoms and is reduced
• During H transfers, electrons loose potential energy which is then released
How Exactly is Energy Harvested from
Glucose
• During glucose oxidation there are two key players:
1. An enzyme called Dehydrogenase
2. A co-enzyme called NAD+

• NAD+ (Nicotinamide Adenine Dinucleotide) is an organic molecule that is used

to shuttle electrons during redox reactions

• Dehydrogenase strips two electrons from glucose

• These two electrons (as H) are picked up by NAD + which becomes NADH + H +
How Exactly is Energy Harvested from
Glucose
• NADH + H+ delivers the electrons to the electron transport chain where
they are then transferred to O2 forming water and creating ATP
• The electron transport chain consists of a series of electron transfers (redox
reactions) that end with O2
• Each of these electron transfers releases a little bit of energy all of which will
be used to produce ATP
 Cellular Respiration: 4 Stages
• There are four key stages that collectively make up cellular respiration:
1. Glycolysis
2. The Intermediate Step
3. The Citric Acid Cycleà also called the TCA (Tricarboxylic Acid) Cycle and the
Kreb’s Cycle
4. Oxidative Phosphorylation

• All three stages occur in prokaryotes and eukaryotes but the location
differs
• 1 occurs in the cytoplasm of
prokaryotes and eukaryotes
• 2 and 3 occur in the cytoplasm of
prokaryotes and in the
mitochondrial matrix of eukaryotes
• 4 occurs in the plasma membrane of
prokaryotes and in the inner
mitochondrial membrane of eukaryotes
 Cellular Respiration: Summary
1. Glycolysis functions to break glucose into two three carbon sugars
called pyruvate

2. The Intermediate step converts pyruvate into acetyl coA

3. The Citric Acid Cycle converts acetyl coA into CO2

• A very small amount of ATP is also produced during stages 1 and 3
• Glycolysis, the intermediate step and the citric acid cycle function to supply
stage 4 (oxidative phosphorylation) with a supply of electrons

4. Oxidative Phosphorylation: makes use of the electron transport chain

and a process called chemiosmosis
• NADH and FADH2 bring the electrons generated during stages 1, 2 and 3 to the
electron transport chain embedded within the inner mitochondrial membrane

• The bulk of ATP produced during cellular respiration occurs during this step as
electrons fall from NADH and FADH2 to O2 releasing lots of energy that is then
used to phosphorylate ATP
 Cellular Respiration: Summary
• The electron transport chain must somehow be coupled to ATP
synthesis
• As the electron transport chain moves electrons down the staircase from
carrier to carrier energy is released and protons are pumped across the inner
mitochondrial membrane into the intermembrane space using this released
energy
• This creates a concentration gradient of H+ across the membrane with a higher
concentration of H+ between the two membranes than in the cytoplasm of the
mitochondria

• Chemiosmosis uses this H+ gradient to

generate ATP driving the diffusion of H+
through ATP synthases which are protein
complexes built into the inner mitochondrial
membrane that are used to synthesize
ATP
 Glycolysis
• This is the first stage of cellular respiration
• Glycolysis literally means the splitting of sugar
which is exactly what happens

• Glycolysis begins with a single molecule of

glucose and ends with 2 molecules of pyruvate
• 1 6C molecule à 2 3C molecules

• The breakdown of glucose into two pyruvate

molecules occurs over 10 different chemical
reactions
• Each reaction is catalyzed by a particular enzyme

• Glycolysis from start to finish generates:

• 2 NADH + H+ from 2 NAD+
• 2 ATP
• The ATP is generated by substrate-level
phosphorylation
 Glycolysis
• Substrate-level phosphorylation:
• The direct transfer of a phosphate group from a substrate molecule to ADP
forming ATP

• This process is responsible for the production of a small amount of ATP

during stages 1 and stage 3

• Following the breakdown of glucose that occurs during glycolysis all of the
energy that is released is stored in the form of ATP and NADH
• The ATP is available for immediate use but the NADH that is produced must first
enter the electron transport chain located in the inner mitochondrial membrane

• The bulk of the energy that is available from glucose is still

stored in the bonds of the 2 pyruvate molecules and goes on
to be harvested in the citric acid cycle
 Pyruvate is Groomed for the Citric
Acid Cycle
• Once the 2 molecules of pyruvate are formed at the end of glycolysis
they move from the cytoplasm of the cell into a mitochondrion

• Pyruvate as it is formed from glycolysis enters the intermediate step

1. A COOH group is removed as a CO2 molecule leaving behind a 2 carbon
molecule

2. The remaining 2 carbon compound is oxidized producing one NADH from NAD+

3. A molecule called coenzyme A (derived from vitamin B) joins to the two carbon
group forming a molecule called acetyl coenzyme A (acetyl CoA)
• Acetyl CoA is a high energy molecule that enters into the citric acid cycle

• For every one molecule of glucose that enters glycolysis, 2 molecules of acetyl CoA are
produced and enter the citric acid cycle
 The Citric Acid Cycle
• The two carbon portion of acetyl CoA participates in the citric acid cycle
• The coenzyme A portion helps the acetyl group enter the citric acid cycle and
will break off and be recycled

• This stage occurs in the mitochondrial matrix and each individual step is
catalyzed by a different enzyme specific for reaction

• This stage releases 2 CO2 molecules as well as

1 ATP via substrate-level phosphorylation
• The ATP is actually produced as an energy
equivalent called GTP

• It also produces 3 NADH from NAD+ and 1 FADH2

from FAD

• Since 2 molecules of acetyl-CoA enter this cycle

the total yield is 2 GTP, 6 NADH and 2 FADH2
• Considerably more energy released than glycolysis
• 2ATP and 2 NADH
 The Citric Acid Cycle
• At this point the breakdown of glucose has generated 4 ATP
equivalents (2 ATP and 2 GTP), 10 NADH and 2 FADH2
• The FADH2 and the NADH must now enter the electron transport chain so that
the high energy electrons may be transferred to O2 producing water and ATP
via oxidative phosphorylation
 The Electron Transport Chain
• The final stage of cellular respiration is oxidative phosphorylation
• This stage involves the electron transport chain and chemiosmosis

• The electron transport chain is built into the inner mitochondrial

membrane
• This membrane is highly folded à large amount of space to house many
electron transport chains and ATP synthase complexes

• The electrons move from NADH and FADH2 through the electron transport
chain to O2 which acts as the terminal electron receptor

• Each oxygen atom (1/2 O2) picks up two electrons in the form of hydrogen
ions, resulting in 2 H20 molecules à products of cellular respiration
 The Electron Transport Chain
• There are four main protein complexes that make up the electron
transport chain (these are embedded within the membrane)
• There are also two mobile electron carriers that shuttle electrons between the
stationary complexes
• All of these carriers bind and then release electrons in redox reactions
• This functions to move the electrons down the energy staircase

• Three of the stationary protein complexes use the energy from the
movement of the electrons to transport H+ from the matrix into the
inter-membranous space where it is less concentrated
• Establishes an H+ gradient with a [higher] in the inter-membranous space than
in the matrix, this gradient can be used to provide the energy needed to form
ATP
 The Electron Transport Chain
• Because the membrane is not permeable to H+ the ion travels down
the newly established concentration gradient through a membrane
protein called ATP synthase
• This movement causes the ATP synthase to spin which actively catalyzes the
attachment of a phosphate group onto ADP generating ATP
• This is called oxidative phosphorylation because energy from oxidation reactions is
used to phosphorylate ADP

• The H+ gradient created during electron transport is used to drive ATP

synthesis via chemiosmosis
 The Effect of Chemicals on Cellular
Respiration
• There are three different categories of poison that effect cellular
respiration:
1. Poisons that Block the Electron Transport Chain
• Retinone is a poison that tightly binds to the first electron carrier in the chain
• This prevents electrons from being transferred further down the electron
transport chain

• Used to kill insects and fish

• Inhibits ATP synthesis and starves an organism’s cells of energy

• Cyanide and carbon monoxide bind to the

fourth electron carrier which blocks the
flow of electrons to O2
• No H+ gradient is generated therefore
no ATP is made
 The Effect of Chemicals on Cellular
Respiration
2. Poisons that Block ATP Synthase
• Ex: oligomycin blocks the flow of protons through the H+ channel in ATP
synthase
• This antibiotic is used topically to combat fungal infections by inhibiting the
production of ATP

3. Poisons that are Uncouplers

• The mitochondrial membrane becomes leaky to H+
• H+ leaks through the membrane depleting the hydrogen ion gradients
• Electron transport continues but ATP is not synthesized
• O2 is still consumed and often at an accelerated rate
• Ex: DNP (dinitrophenol)
 Review of Cellular Respiration
• Per one glucose molecule:
• Glycolysis: occurs in cellular cytoplasm and produces 2 ATP

• The Citric Acid Cycle: occurs in the mitochondrial matrix and produces 2 GTP

• **Above ATP equivalents are produced by substrate-level phosphorylation

• The Electron Transport Chain and Chemiosmosis

• Harvests energy that is stored in NADH and FADH2 produced during glycolysis, the
intermediate step and the citric acid cycle
• ~28 ATP are formed via oxidative-phosphorylation
 Review of Cellular Respiration
• It is assumed that each NADH that transfers a pair of high energy
electrons from glucose to the electron transport chain contributes
enough H+ to the gradient to produce 2.5 ATP

• It is also assumed that each FADH2 generated contributes enough to

the H + gradient to produce only 1.5 ATP
• Because FADH2 enters the electron transport chain at a later spot than NADH

• **The above estimates for NADH and FADH2 are maximums and actual
numbers may be a little bit lower depending on the circumstances
• Ex: some energy that is stored in the H+ gradient may be used for transport
purposes rather than for ATP generation
 The Effect of Oxygen
Concentration on ATP Generation
• Most of the ATP generation from glucose occurs during oxidative
phosphorylation (~28 ATP)
• This requires an adequate O2 supply

• O2 must be present to act as an electron acceptor during the electron

transport chain

• If O2 is not present, chemiosmosis cannot occur and the cell will die from
energy starvation

• Muscle cells as an example are able to continue on for some period of time
without O2, generating ATP via fermentation
 Fermentation
• The ONLY ATP generated during fermentation is that generated during
glycolysis
• The total ATP generated during glycolysis is 2 ATP

• Glycolysis requires no O2 and generates 2 ATP by

oxidizing Glucose to 2 molecules of pyruvate
• Simultaneously reduces 2 NAD+ to 2 NADH

• The 2 ATP produced by fermentation is

considerably less than the 32 ATP produced by
oxidative phosphorylation
• Enough to allow muscle contraction when the
need for ATP is not met by the rate of O2 delivery
• Many microorganisms that are incapable of
oxidative phosphorylation and generate all of
their energy via fermentation

• There are two types of fermentation:

1. Lactic Acid Fermentation
2. Alcohol Fermentation
 Lactic Acid Fermentation
• Lactic acid fermentation is used by muscle
cells and some bacteria
• A few other cell types are also capable of lactic
acid fermentation

• NADH is oxidized to NAD+ while the pyruvate

generated during glycolysis is reduced to
lactate

• During periods of prolonged exercise, muscle

cells switch to lactic acid fermentation
• Lactic acid that builds up is then carried via the
blood to the liver where it is converted back into
pyruvate

• Lactic acid fermentation is used in industry to

generate yogurt and cheese
 Alcohol Fermentation
• This is used to produce wine, beer, and baking
• Yeast accomplish the production of the above products
• Yeast usually use aerobic respiration but switch to alcohol
fermentation when O2 is absent

• Alcohol fermentation generates NAD+ from NADH

while reducing pyruvate to CO2 and ethanol
• The CO2 produced provides the bubbles in champagne
and beer
• It also is what causes dough to rise when yeast is added
• Ethanol produced is toxic to the fermentative organism
• When wine alcohol concentration reaches 14% the yeast
within the container will die

• Obligate anaerobes cannot survive in the presence of O2

• Facultative anaerobes use oxidative phosphorylation when O2

is present but switch to fermentation when O2 is absent
 Glycolysis Evolved Early On
• Glycolysis takes place in every kind of living cell that exists:
• Bacterial cells, liver cells, skin cells, plants cells, fungal cells etc.

• Ancient prokaryotic cells likely made use of glycolysis to generate all

ATP long before the atmosphere contained O2
• Fossils are present from over 3.5 billion years ago
• O2 did not accumulate in the atmosphere until 2.7 billion years ago

• For the billion years that life existed in an O2-free atmosphere glycolysis was
the only means of energy generation

• Glycolysis also does not require any membrane bound organelles

• Membrane bound organelles evolved greater than one billion years after the
prokaryotic cell
 Various Organic Molecules are
Used for Cell Respiration
• Although glucose is the starting point for glycolysis, free glucose is not
common in our diet
• Lipids, proteins, starch and disaccharides such
as glucose are common in our diet

• All of the above molecules can also be

used to generate ATP because they can be
pushed into glycolysis following some
modifications
• Starch and glycogen can be broken down into
glucose via hydrolytic enzymes

• Proteins are broken down into their constituent amino acids

• Most of these amino acids are used to synthesize cellular proteins
• Unused amino acids are converted into glycolysis or citric acid cycle intermediates
so that their energy can be harvested by cellular respiration
• Amino groups that are removed during this process are disposed of in urine as urea
 Various Organic Molecules are
Used for Cell Respiration
• Fats contain a great deal of energy that can be
harvested by glycolysis
• There are a number of hydrogen atoms on a fat
molecule and each of these hydrogen atoms are
energy-rich electrons

• Fats are first broken down into the fatty acid

and glycerol components
• Glycerol is made into a glycolysis intermediate

• The fatty acid tails are made into acetyl coA for
the citric acid cycle

• Broken down like this a gram of fat will provide

twice as much energy as a gram of starch
 Food Molecules and Biosynthesis
• Not all of the food that we eat is
digested in order to generate ATP
• Food is also responsible for providing the
raw materials needed to synthesize
organic molecules

• Cells must be capable of synthesizing raw

materials needed to perform life
functions and generate and maintain
cellular structure

• Amino acids present from protein

digestion can be used directly to
synthesize cellular proteins

• Glycolysis intermediates must first be

converted but may also be used in
biosynthesis
 Food Molecules and Biosynthesis
• Cellular Respiration and biosynthesis are
closely connected to one another
• Feedback inhibition is used in order to prevent
excess production of certain building blocks
• Ex: if there is an abundance of a particular
amino acid, the pathway that is responsible for
its production is turned off
• An end product inhibits an enzyme that
works early on in the amino acid synthesis
pathway
• When the amino acid is depleted, the inhibition
is terminated and production of the amino acid
is turned on once again

• The ability to generate sugars from CO2 and

H2O is not universal
• Animals cells are incapable of this conversion
while plant cells are able to photosynthesize