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Metabolism: sum total of all the

biochemical reactions in the body

1. Catabolic pathways (Catabolism) –

breakdown or digestion of large molecules,
releases energy
2. Anabolic pathways (Anabolism) –
synthesis of larger molecules by joining
smaller molecules, requires energy
- is the process of oxidizing food molecules, like glucose,
to carbon dioxide and water.

- Energy in food molecules is released and converted to

a form that can be used by the cell, which is ATP.

- The term respiration, is often used to mean breathing

or simply “the process of inhaling and exhaling”.

- For clarity, the term cellular respiration is used to refer

specifically to a series of enzymatic reactions that can
occur in the presence or absence of oxygen and make
energy available to the cell
Cellular Respiration is of two-types:
Aerobic and Anaerobic Respiration

aerobic respiration is cellular respiration that occurs in

the presence of oxygen

anaerobic respiration or fermentation is cellular

respiration that occurs in the absence of oxygen

• Both types of cellular respiration begins with glycolysis

- Occurs in the cytoplasm of the cell, in essentially all

- Prokaryotes and eukaryotes both undergo glycolysis

- Glycolysis by itself does release a small amount of energy

from glucose. This reaction is anaerobic because it does
not require oxygen to take place

- It is the initial step in both aerobic and anaerobic


- It occurs in cytoplasmic fluid (cytosol) in an anaerobic

- Glycolysis involves the breakdown of glucose, a six-carbon
sugar, into two molecules of a three-carbon compound
called pyruvate or pyruvic acid.

- It also results in a net energy yield of two ATP molecules

per glucose molecule that enters this reaction.

- Glycolysis needs an input of energy to begin. It takes the

energy in two ATP to start glycolysis.

- The ATP phosphorylates the glucose, energizing it to start

the reaction. As a result of the reactions of glycolysis, four
ATP are generated as well as two molecules of NADH
carrying electrons, so there is a net gain of two ATP for this
STEP 1 to 3 – Glucose molecule is energized, using ATP

In this series of three chemical reactions, glucose is the first

phosphorylated to glucose-6-phosphate (step 1), which is
rearranged to form fructose-6-phosphate (step 2). Another
phosphate group is added to form fructose 1,6-diphosphate
(step 3). The cell invests two molecules of ATP in steps 1 and 3
to energize one glucose molecule and form fructose 1,6-
biphosphate, which is unstable and reactive.

fructose 1,6-diphosphate is converted into two molecules of

glyceraldehyde 3-phosphate (PGAL).

Since there are two molecules of PGAL produced, steps 5 to 9

occur twice per glucose molecule
STEP 5 – reduction of PGAL produces NADH

This step is the first payoff step. PGAL donates a hydrogen

atom and two electrons NAD+, reducing it to NADH.

NADH, an electron carrier, has a similar structure to NADPH

except that it has one less phosphate group attached to the
STEP 6 to 9 – ATP and pyruvic acids are produced.

a sequence of four chemical reactions complete the

breakdown of glucose into two molecules of pyruvic acid.

For every molecule of glucose, four molecule of ATPs are

formed in steps 6 and 9.

Since two molecules of ATP have been invested in the

preparatory phase, a net gain of 2 ATP molecules per glucose
molecule results from glycolysis

• Oxidation of pyruvic acid

The second stage of aerobic respiration is the oxidation of pyruvic

acid. It occurs in the mitochondrial matrix.

In this stage, each molecule of pyruvic acid produced in glycolysis

is oxidized while a molecule of NAD+ is reduced to NADH.

A carbon atom is also removed from pyruvic acid and released as

CO2, forming a two-carbon molecule called acetyl group.

This acetyl group finally combines with a compound derived from

a B vitamin called coenzyme A, forming acetyl-CoA.
The overall reactions can be summarized by the following

Energy is temporarily stored in NADH, will later be used to convert

ADP molecules to ATPs.

The two acetyl-CoA molecules, on the other hand, will proceed to

the third phase of aerobic respiration, that is, the Krebs Cycle.
The Krebs Cycle or Citric Acid Cycle

Each of the acetyl-CoA molecules produced during the oxidation of

pyruvic acid passes through a series of complex chemical reactions
called the Krebs cycle, named after a German scientist, Sir Hans
Kreb (1900-1981), who discovered and studied the workings of
this cycle.

This set of reaction is also referred to as the Citric Acid Cycle.

Like the oxidation of pyruvate molecules, the Krebs cycle also

occurs in the Mitochondrial Matrix.

The cycle begins as enzymes strip the CoA portion from acetyl-
CoA. Only the two carbon acetyl part actually participates in the
Krebs Cycle.
The acetyl group then combines with a four-carbon compound
called Oxaloacetic Acid (already present in the mitochondrion), to
form a 6-carbon compound called Citric Acid.

Citric Acid is then oxidized to form a 5-carbon compound with the

release of CO2. the 5-carbon compound is oxidized to form a 4-
carbon compound also releasing CO2.

Finally this 4-carbon compound is converted through a series of

reactions to oxaloacetic acid, which can again pick up another
acetyl group, thus starting the cycle again.

With every turn of the Krebs cycle, a molecule of acetyl-CoA

produces one molecule of ATP, three molecules of NADH, and a
molecule of FADH2 (flavine adenine dinucleotide, also an electron-
carrier molecule)
Since there two molecules of acetyl-CoA produced in the oxidation
of pyruvic acid, the cycle makes two turns for every glucose
molecules oxidized, thus there is a total of 2 ATP molecules
produced, 6 molecules of NADH, and 2 molecules of FADH2. 4
molecules of CO2 are released as by-products.

The high energy electrons in NADH and FADH2, will be used to

produce ATP molecules in the last stage of aerobic respiration
which involves the electron transport chain.

To summarize, the following are produced for every glucose

molecules that goes through glycolysis and the Krebs cycle:
• 4 ATP molecules
• 10 molecules of NADH
• 2 molecules of FADH2
• 6 molecules of CO2

The 4 ATP molecules gained from glycolysis and Krebs cycle

represent just a small fraction of energy stored in a glucose

Of the remaining energy, some are liberated as heat energy during

the first 3 stages of aerobic respiration. The rest of the energy is
still locked up in the high-energy electrons carried by NADH and

Before this energy can be used, it must be transferred to ATP

molecules through electron transport chain. This process occurs in
the inner membrane of the mitochondrion. It is similar to the
transport of electrons in the thylakoids during photosynthesis.
The transport of electrons begins when high-energy electrons
carried by NADH donate two electrons and a proton to the
electron transport chain.

The electrons are passed from one acceptor to the next down an
energy gradient until they reach the final electron acceptor, which
is oxygen.

FADH2, also donates its high-energy electrons to the electron

transport chain. Since it has a lower energy level than NADH,
FADH2 enters at a lower energy level of the chain.

As electrons move down the chain, H+ ions are pumped across to

the outer compartment of mitochondrion. This increases the
concentration of H+ ions on that side of the mitochondrion.
Because of the presence of a concentration gradient, the H+ ions
then flow back into the mitochondrial matrix passes through ATP
synthase, a special protein channel that converts ADP to ATP. This
process is called chemiosmotic synthesis of ATP. An estimate 36
ATP molecules are gained from the entire process of aerobic

The chemical reactions that release energy from glucose in the

absence of oxygen is called anaerobic respiration. Anaerobic
organisms can survive without oxygen by utilizing the small
amount of energy gained through glycolysis.

There are 2 kinds of anaerobic respiration; alcohol fermentation

and lactic acid fermentation. Both types of fermentation produced
only 2 molecules of ATP which are generated during glycolysis.

The pyruvic acid produced via glycolysis is converted to ethanol or

ethyl alcohol (C6H5OH). This process consists of two steps.

(1) CO2 is released from pyruvate, which is then converted to a 2-

carbon compound called acetylaldehyde

(2) Acetylaldehyde is reduced to ethyl alcohol by NADH. This

generates the supply of NAD needed for glycolysis.

Alcoholic fermentation in yeast is used in brewing and wine-

making. Some bacteria also undergo alcoholic fermentation under
anaerobic conditions

During lactic acid fermentation, pyruvic is directly reduced to lactic

acid by NADH without the release of CO2. This type of
fermentation by certain bacteria and yeast is used in the dairy
industry particularly in making cheese and yogurt.

In human skeletal muscle cells, ATP is produced by lactic acid

fermentation. This occurs in the early stage of a strenuous
exercise, when the rate of glycolysis is faster that the intake of

Under these conditions, the cells switch from aerobic respiration

to fermentation. The accumulated lactic acid causes muscle
fatigue and pain, but is gradually transported by the blood to the
liver. Lactate is converted back to pyruvate by the liver cells.