INTRODUCTION TO BIOLOGY

BIO101

Cellular Respiration
November 3-4, 2022

Dr. Esin Demir

2022-2023 Fall
 Supply of Energy for Metabolic Processes

Photosynthesis
Cellular Respiration

Cellular Respiration:
Aerobic Harvesting of Energy!
Photosynthesis reminder

• 500.000 chloroplasts in 1 mm2 of

leaf

• A leaf ’s green color comes from

chlorophyll, a light-absorbing
pigment in the chloroplasts

• Carbon dioxide enters the leaf,

and oxygen exits, by way of tiny
pores called stroma
 Photosynthesis reminder

• Photosynthesis Under the Microscope

• https://www.youtube.com/watch?v=c7Ya5xoy2nw
 Cellular Respiration

• Cellular respiration: Energy production in the cells

• The responsible organelle is mitochondrion
Mitochondria
 Mitochondria

• How Mitochondria Produce Energy

• Nice animation:

• https://www.youtube.com/watch?v=39HTpUG1Mw
Q
 Two critical events of Ecosystem

Photosynthesis,
• Takes place in a plant cell’s chloroplasts
• The energy of sunlight is used to
rearrange the atoms of carbon dioxide
(CO2) and water (H2O) to produce sugar
and oxygen (O2).

Cellular respiration,
• O2 is consumed as sugar is broken down
to CO2 and H2O
• The cell captures the energy released in
ATP.
• Takes place in the mitochondria of almost
all eukaryotic cells—in the cells of plants,
animals, fungi, and protists.

(Although prokaryotes don’t have

mitochondria, some do break down sugar in
a similar type of oxygen-using respiration.)
Figure 6.1 The connection between photosynthesis and cellular respiration
Campbell Biology Concepts
 Photosynthesis and cellular respiration provide energy for life

• What is misleading about the following statement?

“Plant cells perform photosynthesis, and animal cells perform cellular respiration.”

• The statement implies that cellular respiration does

not occur in plant cells.

• In fact, almost all eukaryotic cells use cellular

respiration to obtain energy for their cellular work.
 Prokaryotes and Oxygen

• Obligate Anaerobes: prokaryotes that cannot live in the presence of oxygen

• Oxygen poisons them

• Obligate Aerobes: prokaryotes that need oxygen in their environment

• Facultative Aerobes: can survive in the presence or absence of oxygen

 Breathing Supplies O2 for Use in Cellular Respiration and Removes O2

Aerobic: Oxygen-requiring
• Respiration as a synonym for
“breathing,” the meaning of its
Latin root.

• Respiration refers to an exchange

of gases: An organism obtains O2
from its environment and
releases CO2 as a waste product.

• Biologists also define respiration

as the aerobic (oxygen-requiring)
harvesting of energy from food
molecules by cells. This process is
called cellular respiration to
distinguish it from breathing.

Figure 6.2 The connection between breathing and cellular Respiration

Campbell Biology Concepts
 Cellular Respiration Banks Energy in ATP Molecules

Exergonic or Endegonic
organic molecules can also
be “burned” in cellular
reaction?
respiration

• Cellular respiration can produce up to 32 ATP molecules for each

glucose molecule, a capture of about 34% of the energy originally
stored in glucose.

• The rest of the energy is released as heat.

• This may seem inefficient, but it compares very well with the
efficiency of most energy-conservation systems- Automobile engine
converts only about 25% of the energy in gasoline to the kinetic
energy of movement

Figure 6.3 Summary equation for cellular respiration

Campbell Biology Concepts
 The Human Body Uses Energy From ATP for All Its Activities

• How great are the energy needs of a cell?

• If ATP could not be regenerated through cellular respiration, you would use up nearly
your body weight in ATP each day.

• Your brain especially requires a huge amount of energy; its cells burn about 120 grams (g)
of glucose a day, accounting for about 15% of total oxygen consumption.

• Maintaining brain cells and other life-sustaining activities uses as much as 75% of the
energy a person takes in as food during a typical day.

The U.S. National Academy of

Sciences estimates that the
average adult needs to take in
food that provides about 2,200
kcal of energy per day, although
the number varies based on age,
sex, and activity level.

Figure 6.4 Energy consumed by various activities

Campbell Biology Concepts
 Cells Capture Energy From Electrons “Falling” From
Organic Fuels to Oxygen

• How do your cells extract energy from glucose?

• During cellular respiration, electrons are transferred from glucose to oxygen,

releasing energy.
• Oxygen attracts electrons very strongly, and an electron loses potential energy
when it is transferred to oxygen.

Redox Reaction: the movement of electrons from one molecule to another is an

oxidation-reduction reaction.
• the loss of electrons from one substance is called oxidation,
• the addition of electrons to another substance is called reduction.

Figure 6.5A Rearrangement of hydrogen atoms (with their electrons) in the redox reactions of cellular respiration
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 Photosynthesis is a Redox Process, as is Cellular Respiration

• Photosynthesis is also a redox (reduction-oxidation) process.

Campbell Biology Concepts

 Cells Capture Energy From Electrons “Falling” From
Organic Fuels to Oxygen

NADH and Electron Transport Chains:

• An important player in the process of oxidizing glucose is a coenzyme
called NAD+
• accepts electrons and becomes reduced to NADH.
• NAD+: nicotinamide adenine dinucleotide
• is an organic molecule that cells make from the vitamin niacin
and use to shuttle electrons in redox reactions

Figure 6.5B A pair of redox reactions occurring simultaneously

Campbell Biology Concepts
 Cells Capture Energy From Electrons “Falling” From
Organic Fuels to Oxygen

• Using the energy hill analogy for electrons rolling from glucose to
oxygen, the transfer of electrons from an organic molecule to NAD+ is
just the beginning.

In a cell, ETC are built into the

inner membrane of a
mitochondrion

Figure 6.5C Electrons releasing energy for ATP synthesis as they roll down an energy hill from NADH through an electron transport chain to O2
Campbell Biology Concepts
 Overview: Cellular Respiration Occurs In Three Main Stages

Cellular respiration occurs in three major stages

1) Organic fuel molecules; glucose, fatty acids, and some amino acids are oxidized to yield two-carbon
fragments in the form of the acetyl group of acetyl-coenzyme A (acetyl-CoA).
2) The acetyl groups are fed into the citric acid cycle, which enzymatically oxidizes them to CO2; the energy
released is conserved in the reduced electron carriers NADH and FADH2.
3) Reduced coenzymes are themselves oxidized, giving up protons (H+) and electrons.

Figure 6.6 An overview of cellular respiration

Campbell Biology Concepts
 Overview: Cellular Respiration Occurs In Three Main Stages

Stage 1: Glycolysis
• Occurs in the cytosol of the cell.
• Glycolysis begins cellular respiration by breaking glucose into two molecules of a
three-carbon compound called pyruvate.
 Overview: Cellular Respiration Occurs In Three Main Stages

Stage 2: Pyruvate oxidation and the citric acid cycle

• Takes place within the mitochondria.
• Pyruvate is oxidized to a two-carbon compound.
• The citric acid cycle then completes the breakdown of glucose to carbon dioxide.
• Thus, the CO2 that you exhale is formed in the mitochondria of your cells during
this second stage of respiration.
 Overview: Cellular Respiration Occurs In Three Main Stages

Stage 3: Oxidative phosphorylation

• Involves electron transport and a process known as chemiosmosis.
• NADH and a related electron carrier, FADH2 (flavin adenine dinucleotide), shuttle
electrons to an electron transport chain embedded in the inner mitochondrial
membrane.
• Most of the ATP produced by cellular respiration is generated by oxidative
phosphorylation, which uses the energy released by the downhill fall of electrons
from NADH and FADH2 to oxygen to phosphorylate ADP.
https://www.differencebetween.com/what-is-the-difference-between-chemiosmosis-in-mitochondria-and-chloroplast/
 Overview: Cellular Respiration Occurs In Three Main Stages

• What couples the electron transport chain to ATP synthesis?

• As the electron transport chain passes electrons down the energy

hill, it also pumps hydrogen ions (H+) across the inner mitochondrial
membrane into the narrow intermembrane space.

• The result is a concentration gradient of H+ across the membrane.

• In chemiosmosis, the potential energy of this concentration gradient

is used to make ATP.
https://ibiologia.com/chemiosmosis/
https://www.istockphoto.com/tr/vekt%C3%B6r/elektron-ta%C5%9F%C4%B1ma-zinciri-%C3%A7iftler-atp-sentezine-kemosentez
gm1272241549-374566858
 Glycolysis Harvests Chemical Energy By Oxidizing Glucose To Pyruvate

• Glycolysis, means “splitting of sugar” (glyco, sweet, and lysis, split).

• The oxidation of glucose to pyruvate during

glycolysis releases energy, which is stored in ATP
and in NADH.

• The cell can use the energy in ATP immediately,

but for it to use the energy in NADH, electrons
from NADH must pass down an electron
transport chain located in the inner
mitochondrial membrane.

• And the pyruvate molecules still hold most of the

energy of glucose; these molecules will be
oxidized in the citric acid cycle.

Figure 6.7A An overview of glycolysis

Campbell Biology Concepts
 Glycolysis Harvests Chemical Energy By Oxidizing Glucose To Pyruvate

Substrate-level phosphorylation: the process of how ATP is formed in glycolysis.

• An enzyme transfers a phosphate group ( P ) from a substrate molecule
directly to ADP, forming ATP.

Figure 6.7B Substrate-level phosphorylation: transfer of a phosphate group from a substrate to ADP, producing ATP
Campbell Biology Concepts
 Glycolysis Harvests Chemical Energy By Oxidizing Glucose To Pyruvate

Energy Investment Phase

Figure 6.7C Details of glycolysis

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 Glycolysis Harvests Chemical Energy By Oxidizing Glucose To Pyruvate

Energy Payoff Phase

Figure 6.7C Details of glycolysis

Campbell Biology Concepts
 Glycolysis Harvests Chemical Energy By Oxidizing Glucose To Pyruvate

For each glucose molecule processed, what are the net molecular products
of glycolysis?

• Two molecules of pyruvate,

• Two molecules of ATP,
• Two molecules of NADH
 Pyruvate is Oxidized in Preparation for the Citric Acid Cycle

• As pyruvate forms at the end of glycolysis, it is transported from the cytosol,

where glycolysis takes place, into a mitochondrion, where the citric acid cycle
and oxidative phosphorylation will occur.

• Pyruvate itself does not enter the citric acid cycle.

• It first undergoes some major chemical “grooming.”
• A large, multi-enzyme complex catalyzes three reactions.

Figure 6.8 The link between glycolysis and the citric acid cycle: the oxidation of pyruvate to acetyl CoA
Campbell Biology Concepts
 The Citric Acid Cycle Completes The Oxidation of Organic Molecules,
Generating Many NADH and FADH2 Molecules

• The citric acid cycle is often called the Krebs cycle in honor of Hans Krebs, the German-
British researcher who worked out much of this pathway in the 1930s.

• The six-carbon compound first formed in the cycle is citrate, the ionized form of citric acid;
hence the name citric acid cycle

• Multiple steps that follow, each catalyzed by a specific enzyme located in the mitochondrial
matrix or embedded in the inner membrane.

Figure 6.9A An overview of the citric acid cycle

Campbell Biology Concepts
https://en.wikipedia.org/wiki/Citric_acid_cycle
 The Citric Acid Cycle Completes The Oxidation of Organic Molecules,
Generating Many NADH and FADH2 Molecules

• Each turn of the cycle makes one

ATP molecule by substrate-level
phosphorylation.

• But it also produces four other

energy-rich molecules: three NADH
molecules and one molecule of
another electron carrier, FADH2.

• Two turns of the cycle occur.

• Overall yield per molecule of glucose

• 2 ATP
• 6 NADH
• 2 FADH2
2 Acetyl-CoA is
produced from 1 Glycolysis+Pyruvate Oxi.+CAC:
single Glucose total of 4 ATP, 10 NADH, and 2 FADH2
 The Citric Acid Cycle Completes The Oxidation of Organic Molecules,
Generating Many NADH and FADH2 Molecules

Figure 6.9B A closer look at the citric acid cycle. (Remember that the cycle runs two times for each glucose molecule oxidized.)
Campbell Biology Concepts
 Most ATP Production Occurs By Oxidative Phosphorylation

• Oxidative phosphorylation: uses the electron transport chain and chemiosmosis

• The arrangement of electron carriers built into a membrane makes it possible to create an
H+ concentration gradient across the membrane and then use the energy of that gradient to
drive ATP synthesis.

• ATP synthase: synthesizes ATP

Figure 6.10A Oxidative phosphorylation: electron transport and chemiosmosis in a mitochondrion

Campbell Biology Concepts
 Most ATP Production Occurs By Oxidative Phosphorylation

• The role of ATP synthase in chemiosmosis

• The H+ concentration gradient across the

membrane stores potential energy, much the way
a dam stores energy by holding back the elevated
water behind it.

• ATP synthase is considered the smallest molecular

rotary motor known in nature.

• Hydrogen ions move one by one into binding sites

within this protein complex (the rotor), causing it
to spin.

• After once around, they are spit out into the

mitochondrial matrix.

• The spinning rotor turns an internal rod, which

activates sites in the catalytic knob that
phosphorylate ADP to ATP.

Figure 6.10B ATP synthase—a molecular rotary motor

Campbell Biology Concepts
 Most ATP Production Occurs By Oxidative Phosphorylation

Figure 6.10 How electron transport drives ATP synthase machines.

Campbell Essential Biology
 Most ATP Production Occurs By Oxidative Phosphorylation

• For the cell to be able to harvest the energy banked in NADH and FADH2, these molecules
must shuttle their high-energy electrons to an electron transport chain.

• There the energy from the oxidation of organic molecules is used to phosphorylate ADP to
ATP—hence the name oxidative phosphorylation.

• What effect would an absence of oxygen (O2) have on the process illustrated in figure?

• Without oxygen to “pull” electrons down the electron transport chain, the energy stored
in NADH and FADH2 could not be harnessed for ATP synthesis.
 Review: Each Molecule of Glucose Yields Many Molecules of ATP

• The number of ATP molecules cannot be stated exactly for several reasons.
• The NADH produced in glycolysis passes its electrons across the mitochondrial membrane to either NAD+ or FAD.
• Because FADH2 adds its electrons farther along the electron transport chain, it contributes less to the H+ gradient and
thus generates less ATP.
• In addition, some of the energy of the H+ gradient may be used for work other than ATP production, such as the active
transport of pyruvate into the mitochondrion.

Figure 6.12 An estimated tally of the ATP produced per molecule of glucose by substrate-level and oxidative Phosphorylation in cellular respiration
Campbell Biology Concepts
Review: Each Molecule of Glucose Yields Many Molecules of ATP
Review: Each Molecule of Glucose Yields Many Molecules of ATP
 Oxidative Phosphorylation

• ATP synthesis by chemiosmosis is similar in bacteria, mitochondria, and

chloroplasts

Figure 12.22
Molecular Cell Biology, Lodish, 2008
Overview of Aerobic Oxidation and Photosynthesis
 Fermentation: Anaerobic Harvesting of Energy

• Fermentation enable cells to produce ATP without oxygen.

• Fermentation is a way of harvesting chemical energy that does not require
oxygen.
• The metabolic pathway that generates ATP during fermentation is glycolysis, the
same pathway that functions in the first stage of cellular respiration.

• To oxidize glucose in glycolysis, NAD+ must be present as an electron acceptor.

• This is no problem under aerobic conditions, because the cell regenerates its pool
of NAD+ when NADH passes its electrons into the mitochondrion, to be
transported to the electron transport chain.

• Fermentation provides an anaerobic path for recycling NADH back to NAD+.

 Fermentation: Anaerobic Harvesting of Energy

Lactic Acid Fermentation

• One common type of fermentation.

• Your muscle cells and certain bacteria can regenerate NAD+ by

this process.

• NADH is oxidized back to NAD+ as pyruvate is reduced to lactate

(the ionized form of lactic acid).

• Muscle cells can switch to lactic acid fermentation when the

need for ATP outpaces the delivery of O2 via the bloodstream.

Figure 6.13A Lactic acid fermentation: NAD+ is regenerated as pyruvate is reduced to lactate
Campbell Biology Concepts
 Fermentation: Anaerobic Harvesting of Energy

• The lactate that builds up in muscle cells during

exercise was previously thought to cause muscle
fatigue and pain, but research now indicates that
increased levels of other ions may be to blame.
• In any case, the lactate is gradually carried away by the
blood to the liver, where it is converted back to
pyruvate and oxidized in the mitochondria of liver cells.
• The dairy industry uses lactic acid fermentation by
bacteria to make cheese and yogurt.
• Other types of microbial fermentation turn soybeans
into soy sauce and cabbage into sauerkraut.
 Fermentation: Anaerobic Harvesting of Energy

Alcohol Fermentation
• Used in brewing, winemaking, and baking.

• Yeasts are single-celled fungi that normally use aerobic

respiration to process their food.
• But they are also able to survive in anaerobic environments.

• Yeasts and certain bacteria recycle their NADH back to NAD+

while converting pyruvate to CO2 and ethanol.

• The CO2 provides the bubbles in beer and champagne.

• Bubbles of CO2 generated by baker’s yeast cause bread dough to

rise.

• Ethanol (ethyl alcohol), the two-carbon end product, is toxic to

the organisms that produce it.

• Yeasts release their alcohol wastes to their surroundings, where it

usually diffuses away. When yeasts are confined in a wine vat,
they die when the alcohol concentration reaches 14%.

Figure 6.13B Alcohol fermentation: NAD+ is regenerated as pyruvate is broken down to CO2 and ethanol
Campbell Biology Concepts
Three Possible Catabolic Fates of the Pyruvate Formed in Glycolysis
 The cells without mitochondria

• Some tissues and cell types (such as erythrocytes,

which have no mitochondria and thus cannot
oxidize pyruvate to CO2) produce lactate from
glucose even under aerobic conditions.
• The reduction of pyruvate in this pathway is
catalyzed by lactate dehydrogenase
Three Possible Catabolic Fates of the Pyruvate Formed in Glycolysis
 Fermentation: Anaerobic Harvesting of Energy

Types of Anaerobes

• Unlike muscle cells and yeasts, many prokaryotes that

live in stagnant ponds and deep in the soil are obligate
anaerobes.

• Yeasts and many other bacteria are facultative

anaerobes.
• On the cellular level, our muscle cells behave as
facultative anaerobes.

• For a facultative anaerobe, pyruvate is a fork in the

metabolic road.
• If oxygen is available, the organism will
always use the more productive aerobic
respiration.

• Thus, to make wine and beer, yeasts must be

grown anaerobically so that they will ferment
sugars and produce ethanol. For this reason, the
wine barrels and beer fermentation vats are
designed to keep air out.

Figure 6.13C Wine barrels and beer fermentation Vats

Campbell Biology Concepts
 Cells Use Many Kinds of Organic Molecules As Fuel
For Cellular Respiration

• A wide range of carbohydrates can

be funneled into glycolysis.

• Fats make excellent cellular fuel

because they contain many
hydrogen atoms and thus many
energy-rich electrons.

• Proteins can also be used for fuel,

although your body preferentially
burns sugars and fats first.

Figure 6.15 Pathways that break down various food molecules

Campbell Biology Concepts
 Cells Use Many Kinds of Organic Molecules As Fuel
For Cellular Respiration

• Animals store most of their energy reserves as

fats, not as polysaccharides. What is the
advantage of this mode of storage for an animal?

• Most animals are mobile and benefit from a

compact and concentrated form of energy storage.
Also, because fats are hydrophobic, they can be
stored without extra water associated with them.
 Organic Molecules From Food Provide Raw Materials For Biosynthesis

• Not all food molecules are destined

to be oxidized as fuel for making ATP.

• Food also provides the raw materials

your cells use for biosynthesis—the
production of organic molecules
using energy-requiring metabolic
pathways.

• Feedback Inhibition in case a an

excess amount of a certain molecule.

Figure 6.16 Biosynthesis of large organic molecules from intermediates of cellular respiration.
Campbell Biology Concepts
 ROS Formation in Mitochondria and Mitochondrial Defenses

ROS: Reactive Oxygen Species

• Photoprotection and tolerance to various stresses in vegetables
• May cause irreversible DNA damage since it oxidize and modify some cellular components.
• Oxidation-Reduction equilibria or redox homeostasis is a key.
• However, pronounced deviations, mainly toward oxidation, may cause damage to
biomolecules, disrupting the physiological redox cell signaling and leading to a transient state
known as OS.

• When the rate of electron entry into the respiratory chain and
the rate of electron transfer through the chain are mismatched,
superoxide radical (･O2–) production increases at Complexes I
and III as the partially reduced ubiquinone radical (･O–)
donates an electron to O2.

• Superoxide acts on aconitase, a 4Fe-4S protein, to release

Fe2+.

• In the presence of Fe2+, the Fenton reaction leads to formation

of the highly reactive hydroxyl free radical (･OH).

• The reactions shown in blue defend the cell against the

damaging effects of superoxide.

• Reduced glutathione donates electrons for the reduction of

• OS is defined as an acute imbalance between the H2O2 and of the oxidized Cys residues (—S—S—) of enzymes
and other proteins, and GSH is regenerated from the oxidized
production of ROS and reactive nitrogen species
form (GSSG) by reduction with NADPH.
(RNS) and antioxidant defense systems, enzymatic,
and non-enzymatic.
https://www.semanticscholar.org/paper/Role-of-Reactive-Oxygen-Species-in-Male-
Fatima/9bac4dde1d72dc32ac3108e1be07d95c9de0b334
https://www.frontiersin.org/articles/10.3389/fenvs.2014.00053/full
Role of NADPH and Glutathione in Protecting Cells Against
Highly Reactive Oxygen Derivatives

• Reduced glutathione (GSH) protects the

cell by destroying hydrogen peroxide
and hydroxyl free radicals.

• Regeneration of GSH from its oxidized

form (GSSG) requires the NADPH
produced in the glucose 6-phosphate
dehydrogenase reaction.
 Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease

• Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation

of senile plaques (SPs) and neurofibrillary tangles (NFTs) in several brain areas such as the hippocampus
and frontal and parietal cortex, among others.
• This accumulation of abnormal aggregates formed by fibrillary amyloid-β (Aβ) peptide and
phosphorylated tau proteins, respectively, leads to cognitive, behavioral, and functional impairment.
• Clinically, AD is characterized by a progressive cognitive decline due to a notable loss of synapses and high
rates of neuronal death.

https://www.frontiersin.org/articles/10.3389/fnins.2019.01444/full
https://sci-hub.st/https://www.sciencedirect.com/science/article/pii/B9780128028100000106
https://www.hindawi.com/journals/omcl/2014/780179/
https://www.semanticscholar.org/paper/Mitochondrial-Dysfunction-Contributes-to-the-of-Cabezas-Opazo-Vergara-
Pulgar/9bd3569837f039c7a98fca9970870fa8256373ac