Biological oxidation

* Biological oxidation is that oxidation which occurs in biological systems to

produce energy.
* Energy is essential for maintenance of structure and function of living cells.
* Energy can be produced by oxidation of food staffs e.g. glucose, FA & AA
* Oxidation can be produced by
- Removal of electrons (most common)
- Removal of hydrogen
- Addition of oxygen (least common)
* As electrons are not stable in the free state, so their removal from a substrate
must be accompanied by their addition to another one i.e. oxidation and
reduction reactions occurs at the same time and known as REDOX reaction
* Redox potential : It is the affinity of a substance to accept electrons
- Oxygen has the highest redox potential +0.82 volt.
- Hydrogen has the lowest redox potential -0.42 volt.
- All other substances are intermediate in between.
* Electrons are transferred from substances of lower redox potential to that of
higher redox potential
*The movements of electrons in the redox potential scale is energy producing
process, the amount of energy depends on the difference in redox potential

Oxido-reductases
Enzymes catalyze oxidation-reduction reactions and are classified into 5 groups:
1- Oxidases

Take hydrogen and add to oxygen to form water

2- Aerobic dehydrogenase

Take Hydrogen and add to oxygen to form hydrogen peroxide

3- Anaerobic dehydrogenases
4- Hydroperoxidases:
5- Oxygenases

Take hydrogen and add to carriers like NAD or FAD

Convert hydrogen peroxide into water

Remove hydrogen and add oxygen to substrate

Electron transport chain

(Redox chain, Respiratory chain)
In non-biological systems, energy is produced in the form of heat by direct
reaction between hydrogen and oxygen.
Then heat can be transformed into mechanical or electric energy.
This process is explosive, inefficient and uncontrolled.
In biologic systems, the cells use electron transport chain to transfer electrons
stepwise from substrates to oxygen.
Thus producing energy gradually to prevent sudden release of huge amount of
energy, which may be wasted or destructive to the cells.
This process is stepwise, efficient and controlled.

Electron transport chain is chain of catalysts of increasing redox

potential. It collects reducing equivalents (hydrogen atoms & electrons) from
substrates transferring it stepwise to be oxidized in a final reaction with
oxygen to form water and energy.

Site: in the inner mitochondrial membrane

Components of the electron transport chain: It is formed of:
a- hydrogen and electron carriers (co-enzymes)
b- Four membrane-bound enzyme complexes
Hydrogen and electron carriers of the electron transport chain
1- NAD+: receives 2 hydrogen atoms from substrates passing them to FMN
2- Flavoproteins: FAD and FMN serve as hydrogen carriers.
- FMN receives 2 hydrogen atoms from NADH+H+ passing them to co-enz Q
- FAD receives 2 hydrogen from substrates passing them to co-enz Q
3- Ubiquinone (coenzyme Q)
- It is a small molecule, freely mobile in the inner mitochondrial membrane.
- Receives two hydrogen atoms from reduced FMN or FAD.
- Reduced coenzyme Q passes the electrons to cytochrome b and releases 2H +
into the mitochondrial matrix.
2

4- Cytochromes
- They are electron carriers transferring electrons from coenz. Q to oxygen.
- Given letter designation a, b, and c according to their order of discovery
- All cytochromes are haemoproteins but they differ in redox potential.
N.B.: The mobile components of the electron transport chain include co-enz Q
& cyt c. they collect reducing equivalents from the other fixed components.
*Enzyme complexes of the electron transport chain
The enzymes of the electron transport chain are organized in the inner
mitochondrial membrane in the form of four enzyme complexes.
1- Complex I: NADH dehydrogenase (NADH-ubiquinone oxidoreductase)
- It is a flavoprotein that contains FMN as well as FeS protein as coenzyme.
- It transfers hydrogen atoms from NADH+H+ to ubiquinone.
2- ComplexII: Succinate dehydrogenase (succinate-ubiquinone oxidoreductase)
-It is a flvoprotein that contains FAD as well as FeS protein as coenzymes.
-It transfers hydrogen atoms from succinate to ubiquinone
3- ComplexIII: ubiquinol dehydrogenase (ubiquinol-cyt c oxidoreductase)
It transfers electrons from ubiquinol to cyt c using cyt b & cyt c1 as coenzymes
4- Complex IV: cytochrome oxidase (cytoch.-oxygen oxidoreductase)
It transfers electrons from cytochrome c to oxygen. It needs cyt a and cyt a 3 as
coenzymes
**In addition to these four enzyme complexes there is a fifth complex (complex
V) which is the ATP synthase that is responsible for synthesis of ATP from
ADP and inorganic phosphate

Sequence of events in redox chains:

The hydrogen atoms produced from oxidation of substrates can enter the
chain through NAD+ or FAD.
The hydrogen atoms are then successively transferred through the respiratory
chain to oxygen to produce water and energy.
NAD+ collects the reducing equivalents from substrates as isocitrate, malate,
-hydroxy acyl CoA and -hydroxy butyrate, while FAD collects the
reducing equivalents from substrates as succinate, acyl CoA and choline.
1- NADH, H+ reacts with FMN (by complex ) so that NAD+ is obtained and
FMNH2 are produced (NADH, H+ + FMN NAD+ + FMNH2)
2- H2 are transferred from FADH2 to CO-Q (by complex )
3- FMNH2 transfer H2 to CO-Q CO-QH2 + FMN (by complex )
4- The 2 hydrogen atoms are then removed from CO-QH2 but they can not be
transferred to cyt b this is because the cytochromes can accept or transfer only
electrons. So at this step the two liberated hydrogen atoms (from CO-QH2) will
be ionized to give 2 hydrogen ions (2H+) and e electrons (2e-)
5- The 2 e- will react with the 2 Fe+3 of cytochrome b reducing them to ferrous
ions (2 Fe+2)
6- Then electrons will be successively transferred to 2 Fe +3 of cytochrome c1, c,
a, a3 (cytochrome oxidase) and ionic oxygen is produced O-7- The negatively charged ionic oxygen attracts 2 hydrogen ions from
mitochondrial matrix to form water at the end of the chain
Isocitrate
Malate
- hydroxyl acy1 CoA
- hydroxyl butyrate

Succinate
Acy1 CoA
Choline
Flavoprotein (FAD)
FeS

NAD

Flavoprotein
(FMN) FeS

Cyt b
Fes

O2
Cyt c1

Cyt c

Cyt a
Cu

Cyt a3
Cu

2H

Sequence of events in the electron transport chain

H2O

Oxidative phosphorylation
*Definition: coupling of the electron transport in respiratory chain with
phosphorylation of ADP to form ATP.
It is a process by which the energy of biological oxidation is ultimately
converted to the chemical energy of ATP.
There are 3 sites of the chain that can give enough energy for ATP synthesis:
Site I between FMN and Co-Q at enzyme complex I
Site II between cyt b and c1 at enzyme complex III
Site III between cyt a and a3 at enzyme complex IV
The number of ATP generated depends on the site at which the substrate is
linked to the respiratory chain:
If substrate is linked to the chain through NAD+, 3 ATP are formed for
each molecule oxidized
If substrate is linked to the chain through FAD, 2 ATP are formed for
each molecule oxidized
FAD
FeS

Succinate

Sites of ATP production by oxidative phosphorylation

NADH+H+

FMN

FeS
Site I

ADP+Pi

ATP

Cyt b

Fe
S Site II

ADP+Pi

Cyt c1

Cytc

ATP

Cyt a

Cu

Cyt a3

O2

Cu

Site III

ADP+Pi

ATP

P/O ratio
It is the ratio of the number of molecules of ADP converted to ATP to the
number of oxygen atoms utilized by respiratory chain.
It is a measure to the efficiency of oxidative phosphorylation.
It is 3/1 if NAD is used and 2/1 if FAD is used.

Mechanism of oxidative phosphorylation

- Chemiosomotic theory:
It suggests that the transfer of electrons through the electron transport
chain causes protons to be Translocated from the mitochondrial matrix to
the intermembrane space at the three sites of ATP production (i.e. it acts
as a proton pump) resulting in an electro-chemical potential difference
across the inner mitochondrial membrane.
The electrical potential difference is due to accumulation of positively
charged hydrogen ions outside the membrane.
The chemical potential difference is due to the difference in PH, being
more acidic outside the membrane.
This electrochemical potential difference drives (forces) ATP synthase to
generate ATP from ADP and inorganic phosphate

ATP (adenosine triphophate)

It's high energy compound which is considered as the energy currency of the cell
- It is a nucleotide formed of adenine, ribose and 3 inorganic phosphates.
- It contains 2 high energy phosphate bonds.
Functions of ATP: It is the source of energy for:
1- Biosynthetic reactions.
2- Muscle contraction.
3- Nerve conduction.
4- Active absorption and secretion.
5- Active transport across biological membranes.
6- Activation of monosaccharide, fatty acids and amino acids.
7- Formation of creatine phosphate, which is the energy store in muscles.
8- Biosynthesis of cAMP.