CELLULAR RESPIRATION

❖ the process that breaks down food molecules, usually in the form of glucose, to turn into carbon dioxide and water.
❖ Chemical equation: C6H12O6 + 6O2 6H2O + 6CO2

The chemical equation of cellular respiration is also a redox reaction. Because glucose has lost an electron, it is said to be
oxidized. Meanwhile, oxygen has gained some electrons, so it is said to be reduced. (NOTE: Hydrogen atom is made up of a
hydrogen ion and free electron, and thus, when these hydrogen atoms are removed from glucose, the same happens to the
electrons.

There are many metabolic reactions involved in cellular respiration, and each is catalyzed by its own enzymes. One important
example is nicotinamide adenine dinucleotide (NAD+), which is a coenzyme in the redox reaction. During oxidation, NAD +
accepts two electrons and a hydrogen ion, producing NADH. The high energy electrons received bay NAD + are transported to the
ETC. Another significant coenzyme in the redox reaction is flavin adenine dinucleotide (FAD). Both NAD+ and FAD are important
electron carriers (coenzymes) in cellular respiration.

NADH and FADH2 give off two hydrogen ions and two electrons
upon oxidation. These electrons will play an important role in
cellular respiration.

PHASES OF CELLULAR RESPIRATION

Aerobic cellular respiration is the process wherein cells break down the nutrients in food and turn them into ATP. This process uses
molecular oxygen in a series of catabolic reactions that break down large molecules to release energy.

1. Glycolysis
- Means “glucose splitting” (from the Greek word glyco, “sweet” or “sugar”, and lysis, “splitting”)
- Reflects the fact that the process involves the splitting of six-carbon sugars into two molecules of pyruvate, a three-carbon
molecule
- First step in either cellular respiration or fermentation
- Occurs in cytoplasm
A. ENERGY-REQUIRING PHASE
1. The first step in glycolysis is catalyzed by Hexokinase. Hexokinase phosphorylates glucose uses ATP as the source
of the phosphate, and produces glucose 6-phosphate, a more reactive form of glucose.
2. Isomerase converts glucose 6-phosphate into one of its isomers, fructose 6-phosphate. An isomerase is an
enzyme that catalyzes the conversion of a molecule into one of its isomers.
3. The phosphorylation of fructose 6-phosphate, catalyzed by the enzyme phosphofructokinase. A second ATP
molecule donates a high-energy phosphate to fructose 6-phosphate, producing fructose-1,6-bisphosphate.
4. The fourth step in the in glycolysis employs an enzyme, aldolase, to cleave fructose-1,6-bisphosphate into two three-
carbon isomers dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate.
5. In the fifth step, an isomerase, transforms the dihydroxyacetone-phosphate into its isomer, glyceraldehyde-3-
phosphate. Thus, the pathway will continue with two molecules of a single isomer. At this point in the pathway, there
is a net investment of energy from two ATP molecules in the breakdown of one glucose molecule.

B. ENERGY-RELEASING PHASE
6. The sixth step in glycolysis oxidizes the sugar (G3P), extracting high-energy electrons, which are picked up by the
electron carrier NAD+, producing NADH. The sugar is then phosphorylated by the addition of second phosphate
group, producing 1,3-bisphosphoglycerate.
7. In the seventh step, catalyzed by phosphoglycerate kinase (an enzyme named for the reverse reaction), 1,3-
bisphosphoglycerate donates a high-energy phosphate to ADP, forming one molecule of ATP. (this is an example of
substrate-level phosphorylation). A carbonyl group on the 1,3-bisphosphoglycerate is oxidized to a carboxyl group,
and 3-phosphopglycerate is formed.
8. In the 8th step, the remaining phosphate group in 3-phosphoglycerate moves from the 3rd carbon to the second
carbon producing 2-phosphopglycerate. The enzyme catalyzing this step is mutase.
9. Enolase catalyzes the 9th step. This enzyme causes the dehydration reaction of 2-phosphoglycerate, resulting in the
formation of a double bond that increases the potential energy in the remaining phosphate bond and produces
phosphoenolpyruvate (PEP).
 10. The last step is catalyzed by the enzyme pyruvate kinase and results in the production of second ATP molecule by
substrate-level phosphorylation and the compound pyruvic acid (or its salt form pyruvate).

NOTE!!!
For every glucose molecule that enters glycolysis, 2 pyruvates, 4 ATP molecules and 2 NADH molecules are produced. The
net ATP yield is 2 ATP molecules for each glucose.

Pyruvate Oxidation Steps

Pyruvate is produced by glycolysis in the cytoplasm, but pyruvate oxidation takes place in the mitochondrial matrix. So before the
chemical reactions can begin, pyruvate must enter the mitochondrion, crossing its inner membrane and arriving at the matrix.
In the matrix, pyruvate is modified in a series of steps:

Step 1. A carboxyl group is snipped off from the pyruvate and released as a molecule of carbon dioxide, leaving behind a two-
carbon molecule.
Step 2. The two-carbon molecule from step 1 is oxidized, and the electrons lost in the oxidation are picked up by NAD + to form
NADH.
Step 3. The oxidized two-carbon molecule – an acetyl group is attached to CoenzymeA (CoA), an organic molecule derived from
Vitamin B5, to form acetyl CoA. Acetyl CoA is sometimes called a carrier molecule, and its job is to carry the acetyl group
to the citric acid cycle.

The steps above are carried out by a large enzyme complex called pyruvate dehydrogenase.

2. Krebs Cycle/Citric Acid Cycle

❖ Occurs in the matrix of the mitochondria.
Step 1. In the first step of the citric acid cycle, acetyl CoA joins with a four-carbon molecule, oxaloacetate, releasing the CoA group
and forming a six-carbon molecule called citrate. A reaction catalyzed by citrate synthase.
Step 2. In the second step, citrate is converted into its isomer, isocitrate. The reaction is catalyzed by the enzyme aconitase.
Step 3. In the third step, isocitrate is oxidized and releases a molecule of carbon dioxide, leaving behind a five-carbon molecule –
α-ketoglutarate. During this step, NAD+ is reduced to form NADH. The enzyme catalyzing this step, isocitrate
dehydrogenase.
Step 4. The fourth step is similar to the third. In this case, its α-ketoglutarate that’s oxidized, reducing NAD+ to NADH and
releasing a molecule a 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.
Step 5. In step 5, Succinyl CoA is converted to succinate in a reaction catalyzed by the enzyme succinyl-CoA synthetase. The
CoA of succinyl CoA is replaced by a phosphate group, which is then transferred to ADP to make ATP. In some cells,
GDP – guanine diphosphate – is used instead of ADP, forming GTP – guanine triphosphate – as a product.
Step 6. In step 6, succinate is oxidized, forming another four-carbon molecule called fumarate. In this reaction, two hydrogen
atoms – with their electrons – are transferred to FAD, producing FADH2. The enzyme (succinate dehydrogenase) 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.
Step 7. In step seven, water is added to the four-carbon molecule fumarate, converting it into another four-carbon molecule called
malate. This reaction is catalyzed by the enzyme fumarase.
Step 8. In the last step of the citric cycle, oxaloacetate – the starting four-carbon compound is regenerated by oxidation of malate
in a reaction catalyzed by malate dehydrogenase. Another molecule of NAD+ is reduced to NADH in the process.

Products of the Citric Acid Cycle: in a single turn of the cycle: 2 carbons enter from Acetyl CoA, and 2 molecules of CO2 are
released
✓ 3 molecules of NADH
✓ 1molecule of FADH2
✓ 1 molecule of ATP
(NOTE: Citric Cycle normally turns twice for every glucose molecule, therefore 6 molecules of NADH, 2 molecules of FADH2
and 2 molecules of ATP are produced.)

3. Electron Transport Chain or Electron Transport System

❖ Occurs in inner membrane of mitochondrion
❖ In this stage, energy from NADH and FADH2 is transferred to ATP
❖ A series of redox reactions that resembles a relay race
❖ Most ATP are synthesized
❖ Oxygen is the final electron acceptor

A. TRANSPORTING ELECTRONS
• high energy electrons are released from NADH and FADH2, and they move along electron transport chains
• as the high energy electrons are transported along the chains, some of their energy is captured
• this energy is used to pump H+ ions (from NADH and FADH2) across the inner membrane, from the matrix into
intermembrane space

B. MAKING ATP
• The pumping of H+ ions across the inner membrane creates a greater concentration of the ions in the intermembrane
space than that in the matrix
• The chemiosmotic gradient cause the ions to flow back across the membrane into the matrix, where their concentration is
lower.
• ATP synthase acts as a channel protein, helping the H + ions cross the membrane. It also acts as an enzyme, forming ATP
from ADP and inorganic phosphate (Pi)
• After passing through the ETC, the “spent” electrons combine with oxygen to form H 2O. therefore, oxygen is needed; in
the absence of oxygen, this process cannot occur
• Oxygen is the final electron acceptor of the electrons removed from the intermediate compounds.

In theory, there are 10 molecules of NADH produced from one glucose molecule. As each NADH enters the electron transport
system, it yields three (3) ATPs. From 10 NADH, it yields up to 30 ATP molecules. Two FADH 2 molecules are produced from the
two rounds of Kreb’s Cycle. The two (2) FADH 2 molecules generate four (4) ATPs. The sum is 38 ATPs per glucose. However,
about two (2) molecules of ATP are used to transport two (2) NADHs that are formed in the cytoplasm. This reduces the production
of ATPs to 36.

FERMENTATION
➢ An important way of making ATP without oxygen
➢ It involves glycolysis but not the other two stages of aerobic respiration

A. LACTIC ACID FERMENTATION

• Pyruvic acid from glycolysis changes to lactic acid
• the fermentation method used by animals and certain bacteria, like those in yogurt
• this type of fermentation is used routinely in mammalian red blood cells and in skeletal muscle that has an insufficient
oxygen supply

B. ALCOHOL FERMENTATION
• The type of fermentation that produces ethanol, an alcohol
• This type of fermentation is carried out by yeasts and some bacteria
• It is used to make bread, wine and biofuels
• This type of fermentation also explains why bread dough rises
KREB’S CYCLE/CITRIC ACID CYCLE/TCA CYCLE
 ELECTRON TRANSPORT SYSTEM

TOTAL ATP PRODUCTION OF AEROBIC CELLULAR RESPIRATION

The sum is 38 ATPs per glucose. However, two (2) molecules of ATP are used to transport two (2) NADHs that are formed
in the cytoplasm. This reduces the production of ATPs to 36.