The National Teachers College

Quiapo, Manila
College of Arts and Sciences

Cellular Respiration: A Closer Look

This Written Output

Is Submitted to:

Prof. Jennifer T. Consing

In Partial Fulfillment of the Requirements for the Subject:

Cell Biology
(SCI MAJ 4)

Submitted by:

Ira Medwin Abalos

Jamila Charissa R. Aldovino
Marielle Gubangco
Kristine M. Garcia
Jan Patrick O. Lorenzo

1st Semester, S.Y. 2018-2019

Introduction.

It is a fact that every living thing needs cellular respiration to survive.

The very idea that the cell is the most basic foundation of life proves that
this process is essential even in complex multicellular organisms like
humans.

Cellular respiration is the process that releases energy by breaking

down glucose and other food molecules mostly in the presence of oxygen.
This process happens through three distinct operations which are glycolysis,
the Krebs cycle, and the electron transport chain. And this process shall be
broken down more in this paper as we discuss further the different processes
that happens during cellular respiration.

What is cellular respiration?

Cellular respiration is the step-by-step release and harness of the

chemical potential energy in glucose. It is the process in which sugar
(glucose) are converted into usable energy (ATP).

The Chemical Pathways

Let’s start first with the source of our own energy. We eat food and
that is the source of energy even of the cells in our body. As we digest food,
it is broken down into simpler molecules called glucose. And the energy in
the food we consume is measured in calories. A calorie is the amount of
energy needed to raise the temperature of 1 gram of water by 1°Celsius.
Alternatively, Calorie with the capital letter C we see on food labels is equal
to 1000 calories.

But then, cells cannot burn glucose or other food compounds

instantaneously. It has to go through a process that gradually release the
energy which is called cellular respiration. This process begins with
Glycolysis which happens in the cytosol. It starts breaking glucose into two
molecules of pyruvate that are oxidized into acetyl CoA. This compound then
enters the citric acid cycle to complete the breakdown of glucose into carbon
dioxide. During the citric acid cycle, the substrate phosphorylation of GDP
form GTP, then converted in ATP. It continues on to electron transport
chains, electron carriers alternate between reduced and oxidized states,
passing on electrons to more electronegative neighbors.
 All the stages described above are involved in the process of cellular
aerobic respiration that takes place inside mitochondria. It provides most of
the energy necessary for cellular processes to animals though fermentation
that makes ATP by lactic acid fermentation in muscle cells in the absence of
oxygen only by using substrate-level phosphorylation of glycolysis can also
provide some energy.

Three Phases of Cellular Respiration

As discussed briefly above, cellular respiration typically involves three

major phases where energy is released and harnessed. In this section we
shall look more closely at each stage to gain further understanding on what
goes or happens in cellular respiration.

Glycolysis

Glycolysis has ten steps, but can be

broken down into just two major
phases: main phases: the energy-
requiring phase, and the energy-
releasing phase. Glycolysis takes
place in the cytosol of a cell and
begins with the energy-requiring
phase. In this stage, the starting
molecule of glucose gets rearranged, and two phosphate groups are
attached to it. The phosphate groups make the modified sugar—now called
fructose-1,6-bisphosphate—unstable, allowing it to split in half and form two
phosphate-bearing three-carbon sugars. Because the phosphates used in
these steps come from ATP, two (2) ATP molecules get used up. The three-
carbon sugars formed when the unstable sugar breaks down are different
from each other. Only one—glyceraldehyde-3-phosphate—can enter the
following step. However, the unfavorable sugar, DHAP can be easily
converted into the favorable one, so both finish the pathway in the end.

Next stage involves energy

release. In this phase, each three-
carbon sugar is converted into another
three-carbon molecule, pyruvate,
through a series of reactions. In these
reactions, two ATP molecules and one
NADH molecule are made. Because this
phase takes place twice, once for each
of the two three-carbon sugars, it
makes four ATP and two NADH overall.

In each reaction in glycolysis is

catalyzed by its own enzyme. The most important enzyme for regulation of
glycolysis is phosphofructokinase, which catalyzes formation of the unstable,
two-phosphate sugar molecule, fructose-1,6-bisphosphate.
Phosphofructokinase speeds up or slows down glycolysis in response to the
energy needs of the cell.

Overall, glycolysis converts one six-carbon molecule of glucose into

two three-carbon molecules of pyruvate. The net products of this process
are two molecules ATP (4 ATP produced minus 2 ATP used up) and two
molecules of NADH.
The Krebs Cycle

The Krebs Cycle or also known as

Citric Acid Cycle is the next phase in
the process of cellular respiration. The
citric acid cycle refers to the first
molecule that forms during the cycle's
reactions—citrate, or, in its protonated
form, citric acid. Alternatively, these
series of reactions are also called
tricarboxylic acid (TCA) cycle, for the three carboxyl groups on its first two
intermediates, or the Krebs cycle, after its discoverer, Hans Krebs.

The Krebs Cycle takes place in the matrix of the mitochondria, just like
the conversion of pyruvate to acetyl CoA. In prokaryotes, these steps both
take place in the cytoplasm. The Krebs cycle is a closed loop; the last part of
the pathway reforms the molecule used in the first step. The cycle includes
eight major steps.
 It begins with the acetyl CoA joining with a four-carbon molecule,
oxaloacetate, releasing the CoA group and forming a six-carbon molecule
called citrate. Then, citrate is converted into its isomer, isocitrate. This is
actually a two-step process, involving first the removal and then the addition
of a water molecule, which is why the Krebs cycle is sometimes described as
having nine steps—rather than the eight listed here.

A f t e r w a r d s
leaving behind a five-carbon molecule—α-
ketoglutarate. During this step, NAD+ is
reduced to form NADH. The enzyme
catalyzing this step, isocitrate
dehydrogenase, is important in regulating
the speed of the citric acid cycle. The fourth step is similar to
the third. In this case, it’s α-ketoglutarate that’s
oxidized, reducing NAD+, to NADH and releasing a
molecule of carbon dioxide in the process.
The remaining four-carbon
molecule picks up Coenzyme A,
forming the unstable compound
succinyl CoA. The enzyme
catalyzing this step, α-ketoglutarate dehydrogenase, is
also important in regulation of the Krebs cycle.
the CoA of succinyl CoA is replaced by a phosphate
group, which is then transferred to ADP to make ATP. In some cells, GDP—
guanosine diphosphate—is used instead of ADP, forming GTP—guanosine
triphosphate—as a product. The four-carbon molecule produced in this step
is called succinate.
 In step six, succinate is oxidized, forming another four-carbon
molecule called fumarate. In this reaction, two hydrogen atoms—with their
electrons—are transferred to FAD producing 2 FADH2. The enzyme that
carries out this step is embedded in the inner membrane of the
mitochondrion, so FADH2 can transfer its electrons directly into the electron
transport chain.

Then, water is added to the four-carbon molecule fumarate, converting

it into another four-carbon molecule called malate. And finally, oxaloacetate
—the starting four-carbon compound—is regenerated by oxidation of malate.
Another molecule of NAD+ is reduced to NADH in the process.

Electron Transport Chain

The Electron Transport Chain is the final step

in aerobic cellular respiration. It is a series
of chemical reactions that produces 34
ATP molecules and H20 from the carrier
molecules that were produced during
the Krebs Cycle.
 It occurs only when oxygen is available whereby the process is a
stepwise movement of electrons from high energy to low energy that makes
the proton gradient. The proton gradient powers ATP production NOT the
flow of electrons. This is shown by the diagram below.

Complex I-IV each play a role in transporting electrons (hence the

name electron transport chain) and establishing the proton gradient. The
only thing you should be concerned with is as electrons pass from complex
to complex (blue arrows), they power the movement of hydrogen atoms
(pink arrows) into the intermembrane space. The number of hydrogen atoms
(also called proton gradient) will build up and flow back to the matrix
simultaneously powering the production of ATP. The movement of molecules
from high to low concentrations requires no energy. This free source of
momentum can be used as energy. In the case of the electron transport
chain the momentum is used to make ATP.

But how do these protons and electrons make it inside of the

mitochondria? Both the Citric Acid Cycle and Electron Transport Chain take
place in the mitochondria. NADH just floats over to the inner-membrane and
can enter the ETC at complex I, while FADH2 enters the transport chain at
complex II. NADH and FADH2 are known as electron carriers. This means
they are capable of donating electrons to the transport chain.

While the electron transport chain’s main function is to produce ATP,

another important byproduct is water. If you follow the path of electrons
(blue) and protons (pink) you might notice that they follow the same basic
pathway until the point where ATP is produced. At the end of the chain the
electrons are taken up by oxygen molecules to make water. This is why
oxygen is known as the final electron acceptor.

Within the electron transport chain, energy is generated through the

process called chemiosmosis. Though, more broadly, chemiosmosis can refer
to any process in which energy stored in a proton gradient is used to do
work. Although chemiosmosis accounts for over 80% of ATP made during
glucose breakdown in cellular respiration, it’s not unique to cellular
respiration. For instance, chemiosmosis is also involved in the light reactions
of photosynthesis.

Chemiosmosis process goes like this. Complexes I, III, and IV of the

electron transport chain are proton pumps. As electrons move energetically
downhill, the complexes capture the released energy and use it to pump H +
ions from the matrix to the intermembrane space. This pumping forms an
electrochemical gradient across the inner mitochondrial membrane. The
gradient is sometimes called the proton-motive force, and you can think
of it as a form of stored energy, kind of like a battery.

Like many other ions, protons can't pass directly through the
phospholipid bilayer of the membrane because its core is too hydrophobic.
Instead, H+ ions can move down their concentration gradient only with the
help of channel proteins that form hydrophilic tunnels across the membrane.

In the inner mitochondrial membrane, H + ions have just one channel

available: a membrane-spanning protein known as ATP synthase.
Conceptually, ATP synthase is a lot like a turbine in a hydroelectric power
plant. Instead of being turned by water, it’s turned by the flow of H + ions
moving down their electrochemical gradient. As ATP synthase turns, it
catalyzes the addition of a phosphate to ADP, capturing energy from the
proton gradient as ATP.

Anaerobic Respiration

In the absence of oxygen, cells take a shortcut in the process of

cellular respiration. After glucose is broken down into pyruvate, a different
process takes place though it produces less ATP and is characteristic of
anaerobic respiration.

Anaerobic cellular respiration is similar to aerobic cellular respiration in

that electrons extracted from a fuel molecule are passed through an electron
transport chain, driving ATP synthesis. Some organisms use sulfate, as the
final electron acceptor at the end of the transport chain, while others use
nitrate, sulfur, or one of a variety of other molecules.

Some prokaryotes that live in low-oxygen environments rely on

anaerobic respiration to break down fuels. For example, some archaea called
methanogens can use carbon dioxide as a terminal electron acceptor,
producing methane as a by-product. Methanogens are found in soil and in
the digestive systems of ruminants, a group of animals including cows and
sheep. Similarly, sulfate-reducing bacteria and Archaea use sulfate as a
terminal electron acceptor, producing hydrogen sulfide (H 2S) as a byproduct.

Fermentation

Fermentation is another anaerobic pathway for breaking down glucose,

one that's performed by many types of organisms and cells. In fermentation,
the only energy extraction pathway is glycolysis, with one or two extra
reactions tacked on at the end.

Fermentation and cellular respiration begin the same way, with

glycolysis. In fermentation, however, the pyruvate made in glycolysis does
not continue through oxidation and the citric acid cycle, and the electron
transport chain does not run. Because the electron transport chain isn't
functional, the NADH made in glycolysis cannot drop its electrons off there to
turn back into NAD+.

The purpose of the extra reactions in fermentation, then, is to

regenerate the electron carrier NAD+ from the NADH produced in glycolysis.
The extra reactions accomplish this by letting NADH drop its electrons off
with an organic molecule (such as pyruvate, the end product of glycolysis).
This drop-off allows glycolysis to keep running by ensuring a steady supply
of NAD+.

Most common type of fermentation are Lactic Acid Fermentation and

Alcohol Fermentation which shall be discussed in the following paragraphs.

Lactic Acid Fermentation

 In lactic acid fermentation, NADH transfers its electrons directly to
pyruvate, generating lactate as a byproduct. Lactate, which is just the
deprotonated form of lactic acid, gives the process its name. The bacteria
that make yogurt carry out lactic acid fermentation, as do the red blood cells
in your body, which don’t have mitochondria and thus can’t perform cellular
respiration.

Muscle cells also carry out lactic acid fermentation, though only when
they have too little oxygen for aerobic respiration to continue—for instance,
when you’ve been exercising very hard. It was once thought that the
accumulation of lactate in muscles was responsible for soreness caused by
exercise, but recent research suggests this is probably not the case.

Lactic acid produced in muscle cells is transported through the

bloodstream to the liver, where it’s converted back to pyruvate and
processed normally in the remaining reactions of cellular respiration.

Alcohol Fermentation
 Another familiar fermentation process is alcohol fermentation, in which
NADH donates its electrons to a derivative of pyruvate, producing ethanol.

Going from pyruvate to ethanol is a two-step process. In the first step, a

carboxyl group is removed from pyruvate and released in as carbon dioxide,
producing a two-carbon molecule called acetaldehyde. In the second step,
NADH passes its electrons to acetaldehyde, regenerating NAD+ and forming
ethanol.

Alcohol fermentation by yeast produces the ethanol found in alcoholic

drinks like beer and wine. However, alcohol is toxic to yeasts in large
quantities (just as it is to humans), which puts an upper limit on the
percentage alcohol in these drinks. Ethanol tolerance of yeast ranges from
about 5% to 21%, depending on the yeast strain and environmental
conditions.

Comparing Aerobic and Anaerobic Respiration

The main goal of cellular respiration is the production of energy in the

form ATP. Aerobic Respiration relies on the three process namely glycolysis,
krebs cycle and electron transport chain while anaerobic respiration relies on
glycolysis and fermentation. In terms of ATP yield, aerobic produces 36 ATP
molecules per 1 molecule of glucose compare to anaerobic that can only
produce 2 ATP molecules per 1 molecule of glucose. Evidently, aerobic
respiration is significantly more efficient than anaerobic respiration.

Application of Cellular Respiration in the Field

Food and Beverage

Fermentation is not only a biological process, but a critical component

of making alcohol and bread. Cultures around the world and throughout
history have used fermentation to produce beer, wine and bread.

Human use of fermentation goes way back—ancient civilizations made

alcohol, as early as nine thousand years ago in Neolithic China. Some
researchers believe humans started growing crops so that they could make
fermented beverages from them. One of the first crops grown during the
agricultural revolution was barley. Since beer is made from barley, anyone
who wanted to brew (and drink) beer would have to grow the barley first.
Then they had to stick around to brew the beer. Ancient people said goodbye
to their previously nomadic lives, planted barley, and became the first
farmers and brewers. The first brewers probably stumbled upon beer by
accident, but they quickly figured out how to keep making it, and today
brewing is down to a science.

Alcoholic beverages are not only vices but real economic commodities.
It also transcends culture. There’s no country that we know do not drink
beer or wine. Plus, it has been shown that there are health benefits to
drinking alcoholic beverages.

A drink (or two) a day can be beneficial to one’s health. Studies have
shown that drinking red wine in moderation lowers your risk of
cardiovascular disease and cancer.
 Men should drink no more than three standard drinks a day; and
women, no more than two. A standard drink refers to 2/3 of a small can of
regular beer (220ml), a glass of wine (100ml) or one nip of spirit (30ml).

In 2011, researchers from the Institute for Population and Public Health at
the University of Calgary, Canada showed that there was a 14 to 25 per cent
reduction in heart disease in moderate drinkers compared with those who had
never consumed alcohol. Other studies have found health benefits of moderate
alcohol consumption related to anti-ageing, lowering the risk of obesity and
improving cognitive function.

Medical Applications

In the arena of medicine, cellular respiration or at least the process

involved in it are creating ways for better healthcare. Aside from the above-
mentioned natural health benefits of wine and beer that are produced by
cellular respiration, fermentation now refers to an industrial process of
manufacturing a wide variety of metabolites and biomaterials by using
microorganisms or mammalian cells in a controlled culture environment.

Fermentation can be performed in batch mode, continuous mode or in

a combinatory, fed-batch mode, depending on the product of interest.
Fermentation technology has long been known for the production of various
medically important products such as antibiotics, solvents such as ethanol,
intermediary compounds such as citric acid, probiotics such as yoghurt etc.

New generation fermentation products include anti-viral drugs,

therapeutic recombinant proteins and DNA, and monoclonal antibodies.
Apart from the drugs, fermentation is also used for the commercial
production of materials required for the development of diagnostic kits, drug
delivery vehicles and medical devices.
 Fermentation technology remains at the heart of rapidly growing
biopharmaceutical industry today, which is expected to expand even more in
the days ahead, in parallel with the progress in novel, targeted drug
discovery.