GENERAL BIOCHEMISTRY II (BCH 202)

TOPIC: BIOLOGICAL OXIDATION

LECTURER: DR OLUGBENGA OGUNLABI (DEPARTMENT OF BIOCHEMISTRY, OOU)

Biological oxidation

Biological oxidation is an energy-producing reaction in living cells, and it is coupled

with a reduction reaction. When a compound loses an electron (oxidized), another
compound gains the electron (or is reduced). Oxidation-reduction (redox) reactions
represent the main source of biological energy. Oxidation and reduction reactions
occur simultaneously, and one does not occur without the other. Chemically,
oxidation is defined as the removal of electrons and reduction as the gain of
electrons. Thus, oxidation is always accompanied by reduction of an electron
acceptor. This principle of oxidation-reduction applies equally to biochemical systems
and is an important concept underlying understanding of the nature of biologic
oxidation. Many biologic oxidations can take place without the participation of
molecular oxygen (eg dehydrogenations). The life of higher animals is absolutely
dependent upon a supply of oxygen for respiration, the process by which cells derive
energy in the form of ATP from the controlled reaction of hydrogen with oxygen to
form water. In addition, molecular oxygen is incorporated into a variety of substrates
by enzymes designated as oxygenases; many drugs, pollutants, and chemical
carcinogens (xenobiotics) are metabolized by enzymes of this class, known as the
cytochrome P450 system,

Redox Potential

In a redox (reduction-oxidation) reaction, electrons are transferred from an electron

donor (or electron "source") to an electron acceptor (or electron “sink”). The
electron source becomes oxidized while the electron sink becomes reduced. The
tendency for molecules to gain electrons is measured as the reduction potential.
The opposite, oxidation potential, can also be used to discuss redox reactions.

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However, in contemporary practice, the reduction potential value is used and refer
to as redox potential (Eº) values. These values are related to thermodynamics
and to the values of K and Gibbs free energy (∆Go).

Standard reduction potential

A redox reaction can be viewed as two reduction half-reactions. The potential of

the reduction half-reaction is used to determine whether a redox reaction is
favorable or not. Each reduction half reaction is written with the thing being reduced
(electron "sink") on the left and the thing being oxidized (electron "source") on the
right.

For example the following redox reaction,

Zn + Cu2+ → Zn2+ + Cu

can be viewed as two reduction half-reactions:

Zn2+ + 2e− → Zn Eº = − 0.76181 Volts

Cu2+ + 2e− → Cu Eº = + 0.3372 Volts

Spontaneous reactions have a Eºoverall > 0 according to the following equation:

Eºoverall = Eºthing being reduced - Eºthing being oxidized

In the equation above, Eº is the standard reduction potential; the reduction potential
of the half-reaction at standard conditions. Note that standard conditions are those
at standard temperature and pressure, and at pH = 0. However, these are not
biological conditions!

How then do biological systems achieve favourable redox potentials?

Biologica oxidation is made possible through the actions of specialised enzymes and
co-enzymes.

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During the process of biological oxidation, high energy compounds are converted to
low energy compound with the release of energy.

Enzymes of biological oxidation belongs to the oxidoreductase enzyme class which

include the following subclasses

o Oxidase
o Dehydrogenase
o Hydroperoxidase
o Oxygenase

These enzymes are aided by the action of the following co-enzymes:

o NAD+
o NADP+
o FMN
o FAD

Oxidase

An oxidase is an enzyme that catalyses the oxidation-reduction reaction, involving

dioxygen (O2) as the electron acceptor. In reactions involving donation of a
hydrogen atom, oxygen is reduced to water (H2O) or hydrogen peroxide (H2O2).
Some oxidation reactions, such as those involving monoamine oxidase or xanthine
oxidase, typically do not involve free molecular oxygen.

An important example is cytochrome c oxidase, the key enzyme that allows the body
to employ oxygen in the generation of energy and the final component of the
electron transfer chain. Other examples are:

1. Glucose oxidase
2. Monoamine oxidase
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 3. Cytochrome P450 oxidase
4. NADPH oxidase
5. Xanthine oxidase
6. L-gulonolactone oxidase
7. Laccase
8. Lysyl oxidase
9. Polyphenol oxidase
10. Sulfhydryl oxidase. This enzyme oxidises thiol groups

Dehydrogenase

A dehydrogenase is an enzyme belonging to the group of oxidoreductases that

oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a
flavin coenzyme such as FAD or FMN. Dehydrogenase catalyses both the reverse and
forward reactions, and in some cases this has physiological significance: for
example, alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde
in animals, but in yeast it catalyzes the production of ethanol from acetaldehyde.

Peroxidases

Peroxidases, also known as peroxide reductases are a large group of enzymes which
play a role in various biological processes. They commonly catalyse the reduction of
hydrogen peroxide to water.

Oxygenase

An oxygenase catalyse the oxidation of substrates by transferring oxygen from

molecular oxygen O2 to it. Oxygenases consist of both constitutive and inducible
isozymes which are a major intracellular source of iron and carbon monoxide.

There are two types of oxygenases:

Monooxygenases, or mixed function oxidase, transfer one oxygen atom to the

substrate, and reduce the other oxygen atom to water.

Dioxygenases, or oxygen transferases, incorporate both atoms of molecular oxygen

(O2) into the product(s) of the reaction.

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Among the most important monooxygenases are the cytochrome P450 oxidases,
responsible for breaking down numerous chemicals in the body

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Oxidative Phosphorylation

Oxidative phosphorylation is the metabolic pathway in which electrons are

transferred from electron donors to electron acceptors in redox reactions; this series
of reactions releases energy which is used to form ATP. Oxidative phosphorylation is
a highly efficient method of producing large amounts of ATP (the basic unit of
energy for metabolic processes). During this process electrons are exchanged
between molecules which create a chemical gradient that allows for the
production of ATP. The most vital part of this process is the electron transport
chain, which produces more ATP than any other part of cellular respiration

Electron Transport Chain

The electron transport chain is the final component of aerobic respiration and is the
only part of glucose metabolism that uses atmospheric oxygen. Electron transport is
a series of redox reactions that resemble a relay race. Electrons are passed rapidly
from one component to the next to the endpoint of the chain, where the electrons
reduce molecular oxygen, producing water.

A complex is a structure consisting of a central atom, molecule, or protein weakly

connected to surrounding atoms, molecules, or proteins. The electron transport
chain is an aggregation of four of these complexes (labeled I through IV), together
with associated mobile electron carriers. The electron transport chain is present in
multiple copies in the inner mitochondrial membrane of eukaryotes and the plasma
membrane of prokaryotes.

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Fig 1: The electron transport chain is a series of electron transporters
embedded in the inner mitochondrial membrane that shuttles electrons from NADH
and FADH2 to molecular oxygen. In the process, protons are pumped from the
mitochondrial matrix to the intermembrane space, and oxygen is reduced to form
water.

There are four protein complexes (labeled complex I-IV) in the electron transport
chain, which are involved in moving electrons from NADH and FADH2 to molecular
oxygen.

1. Complex I establishes the hydrogen ion gradient by pumping four hydrogen

ions across the membrane from the matrix into the intermembrane space.
2. Complex II receives FADH2, which bypasses complex I, and delivers electrons
directly to the electron transport chain.
3. Ubiquinone (Q) accepts the electrons from both complex I and complex II
and delivers them to complex III.
4. Complex III pumps protons through the membrane and passes its electrons
to cytochrome c for transport to the fourth complex of proteins and enzymes.

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 5. Complex IV reduces oxygen; the reduced oxygen then picks up two hydrogen
ions from the surrounding medium to make water.

Key Terms

 prosthetic group: The non-protein component of a conjugated protein.

 complex: A structure consisting of a central atom, molecule, or protein weakly
connected to surrounding atoms, molecules, or proteins.
 ubiquinone: A lipid soluble substance that is a component of the electron
transport chain and accepts electrons from complexes I and II.

Inhibitors of the electron transport chain

Site of Effect on oxidative

Compounds Use
action phosphorylation

Inhibit the electron transport

Cyanide chain by binding more strongly
Carbon monoxide Complex than oxygen to the Fe–
Poisons
Azide IV Cu center in cytochrome c
Hydrogen sulfide oxidase, preventing the
reduction of oxygen

Inhibits ATP synthase by

Oligomycin Antibiotic Complex V blocking the flow of protons
through the Fo subunit

Poisons,
CCCP Inner Ionophores that disrupt the
weight-
2,4-Dinitrophenol [N 1]
membrane proton gradient by carrying
loss protons across a membrane.

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 This
ionophore uncouples proton
pumping from ATP synthesis
because it carries protons
across the inner mitochondrial
membrane

Prevents the transfer of

electrons from complex I to
Rotenone Pesticide Complex I
ubiquinone by blocking the
ubiquinone-binding site

Competitive inhibitors of
Complex
Malonate and oxaloacetate Poisons succinate dehydrogenase
II
(complex II).[95]

Binds to the Qi site

Complex of cytochrome c reductase,
Antimycin A Piscicide
III thereby inhibiting
the oxidation of ubiquinol.

Site of Effect on oxidative

Compounds Use
action phosphorylation

Cyanide Inhibit the electron transport

Carbon monoxide Complex chain by binding more strongly

Poisons
Azide IV than oxygen to the Fe–

Hydrogen sulfide Cu center in cytochrome c

oxidase, preventing the

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 reduction of oxygen

Inhibits ATP synthase by

Oligomycin Antibiotic Complex V blocking the flow of protons
through the Fo subunit.

Ionophores that disrupt the

proton gradient by carrying
protons across a membrane.
Poisons, This
CCCP Inner
weight- ionophore uncouples proton
2,4-Dinitrophenol membrane
loss pumping from ATP synthesis
because it carries protons
across the inner mitochondrial
membrane

Prevents the transfer of

electrons from complex I to
Rotenone Pesticide Complex I
ubiquinone by blocking the
ubiquinone-binding site

Competitive inhibitors of
Complex
Malonate and oxaloacetate Poisons succinate dehydrogenase
II
(complex II)

Binds to the Qi site

Complex of cytochrome c reductase,
Antimycin A Piscicide
III thereby inhibiting
the oxidation of ubiquinol.

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