Many metabolic reactions in the living systems are
oxidation-reduction reactions.
Chemically,
Oxidation is defined as addition of oxygen or removal of
electrons.
Reduction is defined as removal of Oxygen or gain of
electrons Oxidation is always accompanied by reduction of an electron
acceptor. These reactions are also known as redox reactions.
In redox reactions free energy change is proportionate
to the tendency of reactants to donate or accept electrons. Hence,
the change in the free energy can be expressed as redox potential.
Redox reactions can be divided into half reactions. A
half reaction consists of an electron donor and its conjugate
electron acceptor.
Eg. Fe3+ + Cu+ ______________>
Fe2+ + Cu2+ can be divided as
Fe3+ +
e- <______________> Fe2+
(reduction)
Cu+ <__________________>
Cu2+ + e_ (oxidation)
For electrons to be trasferred both half reactions
should occur simultaneously. e- are half reaction's
common intermediate.
The two half reactions of a redox reaction, each
consisting of a conjugate redox pair, can be physically separated to
form an electrochemical cell.
In such a device each half reaction takes place in
separate half cell, and e- are passed between half cells as an
electric current in the wire connecting their two electrodes. A salt
bridge completes the electric circuit by providing a conduit for ions
to migrate and there by maintaining neutrality.
The free energy of a redox reaction can be determined by
measuring the voltage difference between its two half cells.
The equation to measure redox potential is formulated by
Walther Nernst in 1881.
Consider
Aoxn+ + Bred
<________________> Ared + Boxn+
in which n electrons per mole of reactants are
transferred from reductant ( Bred ) to oxidant
( Aoxn ). The equation for the redox potential
can be written as
∆G= ∆G0'
+ RT ln ([
Ared ][Boxn+
] / [ Aoxn+]]
[ Bred
])
∆G= -nF∆E
∆E=∆E0' - RT/nF In([ Ared ][Boxn+ ] / [ Aoxn+]] [ Bred ])
where E= reduction potential
∆E=∆E0' - RT/nF In([ Ared ][Boxn+ ] / [ Aoxn+]] [ Bred ])
where E= reduction potential
∆E=
Electromotive force
(
electron pressure that the electrochemical cell exerts)
The reduction potential when
all components are in their standard state is called standard
reduction potential.
The redox potential of a
redox couple is estimated by measuring the EMF of sample half cell
connected to a standard half cell. The sample half cell contains
1molar solution each of the reductant and oxidant. The reference half
cell has 1M H+ solution
in equilibrium with hydrogen gas at 1atm pressure. The reference half
cell has a reduction potential of 0V. But, in biological systems, the
redox potential is normally expressed at pH 7.0, at which hydrogen
electode is 0.421V
Redox biologically important
systems
Negative and positive redox
potential:
when a substrate has lower
affinity for electrons than hydrogen, it has a negative redox
potential.
If the substance has a
positive redox potential, it has a higher affinity for electrons than
hydrogen.
Thus, NADH, a strong reducing
agent has a negative redox otential where as a sterong oxidant like
Oxygen has a positive redox potential.
Enzymes involved
in oxidation reduction reactions are called oxidoreductases. They can
be classified as
1. Oxidases
2. Dehydrogenases
- Hydroperoxidases
- Oxygenases
Oxidases:
Oxidases catalyze the removal
of Hydrogen from substrate which is accepted byOxygen. They form
mostly water, sometimes Hydrogen peroxide as a reaction product.
AH2 + ½
O2 ------------------> A + H2O
AH2 + O2 ---------------------> A + H2O2
This group includes Cytochrome
oxidase, Tyrosinase, polyphenol oxidase, catachol oxidase and
monoamine oxidase etc.
Cytochrome oxidase
It is a haemoprotein having
heme as the prosthetic group. It is the terminal component of
electron transport chain, and transfers electrons (obtained from the
oxidation of substrate molecules by dehydrogenases) to the their
final acceptor, Oxygen.
The enzyme is poisoned by
Carbon monoxide, cyanide and Hydrogen sulfide. It used to be termed
as cytochrome a3 which
is now termed as cytochrome aa3.
It contains two molecules of heme, each having one Fe atom that oscillates between Fe3+
and Fe2+.
It also contains two atoms of Copper.
Some oxidases are flavo
proteins. They contain FMN ( Flavin mono nucleotide) or FAD (Flavin
adenine dinucleotide) as prosthetic groups. Riboflavin is required
for the formation of FMN and FAD in body.
Examples of flavoprotein
enzymes are L-aminoacid oxidases, xanthine oxidase and aldehyde
dehydrogenase
Dehydrogenases:
these enzymes catalyze the
removal of hydrogen from a substrate but oxygen can not act as the
Hydrogen acceptor. They catalyze the reversible transfer of Hydrogen
from one substrate to another thus bringing abou oxidation and
reductions. The often require co enzymes as acceptors of Hydrogen
atoms.
A large number of enzymes
belong to this group.
NAD+
(Nicotinamide adenine dinucleotide) dependent dehydrogenases:
NAD+
is derived from nicotinic acid, a member of vitamin B-complex. When
NAD+
accepts two Hydrogen atoms, one f the hydrogen atom is removed from
the substrate as such. The other Hydrogen atom is split into one
Hydrogen ion and one electron. The elctron is accepted by NAD+
to neutralize the positive charge on the co enzyme molecule. The
remaining Hydrogen ion is released into the surrounding medium.
H2
-----------------> H + H+ + e-
AH2 + NAD+
-----------------> A + NADH +H+
NAD+
linked dehydrogenases are
- Glyceraldehyde-3- phosphate dehydrogenase
- Isocitrate dehydrogenase
- Malate dehydrogenase
- Glutamate dehydrogenase
- beta hydroxy acyl co A dehydrogenase
- Pyruvate dehydrogenase
- α keto glutarate dehydrogenase
NADP+
(Nicotinamide
adenine dinucleotide phosphate) linked dehydrogenases:
they take part in reductive
biosynthetic reactions like extra mitochondria pathway of fattyacid
synthesis and steroid synthesis. They aso articipate in pentose
phosphate pathway.
Eg. HMG coA reductase, enoyl
reductase
FAD linked dehydrogenases:
Unlike NADP+
and NAD+
dehydrogenases, FAD accepts
both the Hydrogen atoms.
eg. Succinate dehydrogenase,
acyl coA dehydrogenase
Cytochromes:
All
the cytochromes of electron transport chain except cytochrome aa3
belong
to this group.
All cytochromes are heme
proteins having iron atom.
Hydroperoxidases:
They use Hydrogen peroxide and
any organic peroxide as substrate. Two types of enzymes fall in this
category.
- Peroxidases
- catalases
Hydroperoxidases protect the
body against harmful peroxidases. Accumulation of peroxides leads to
the generation of free radicals which may cause cancer and
atherosclerosis.
Peroxidases:
they reduce peroxides using various electron acceptors such as
ascorbate, quinones, and cytochrome C. The reaction catalyzed by
peroxides is complex but the overall reaction is as follows:
H2O2
+ AH2
------Peroxidase-----> 2H2O
Examples of peroxidases are
glutathione peroxidase in RBC which contains Selenium as prosthetic
group, leucocyte peroxidase and Horse radish peroxidase.
Catalases:
It is a heme protein containing four heme groups. Catalases use H2O2
as both electron donor and acceptor.
2H2O
------Catalase------> 2H2O
+ O2
Caalase
is fund in blood, bone marrow, mucus membrane, kidney and liver. It
destructs the H2O2
found by the action of oxidases.
Peroxisomes are subcellular
organelles having both oxidase and catalase activity.
Oxygenases:
This group of enzymes catalyze
direct direct transfer and incorporation of Oxygen into the substrate
molecule.
The catalytic reaction of
oxygenase occurs in two steps:
- Oxygen is bound to enzyme at active site
- the bound oxygen is transferred to substrate
Oxygenases may be subdivided
into
a. monooxygenases
b. dioxygenases
a. Monooxygenase:
They are also known as mixed
function oxidases. They catalyze the incorporation of one atom of
oxygen, while the other atom is reduced to H2O. These
enzymes are also called Hydroxylases because OH group is incorporated
into the substrate. NADPH usually provides reducing equivalents.
Examples of monooxygenases are
- phenyl alanine hydroxylase,
- hydroxylase,
- tryptophan hydroxylase
- Nitricoxide synthase
- Mitochondrial cytochrome P 450 monooxygenase450 denotes that it absorbs light at 450nm, when the heme combines with Carbon Monoxide. It is required for steroid hydroxylation in adrenal cortex, testis and ovary
b.
Dioxygenases:
They incorporate both atoms of
molecular Oxygen into the substrate.
A
+ O2
----------------->AO2
Superoxide dismutase:
Transfer
of single electron to O2
generates Superoxide free radical which is potentially damaging by
giving rise to free radical chain reaction. The enzyme superoxide
dismutase is responsible for the removal of superoxide anion.
The enzyme occurs in all major
tissues in the mitochondria and cytosol.