based on BSC and MSC courses

1. Free radicals
Introduction formation – photolysis, thermolysis, redox
reactions, radical reactions with biomolecules.
INTRODUCTION
A free radical is defined as a molecule or a molecular species that
contains one or more
unpaired electrons, and is capable of independent existence.

2. Types:
Oxygen is required in many metabolic reactions,
particularly for the release of energy.During these
processes, molecular O2 is completely reduced, and
converted to water.However, if the reduction of O2 is
incomplete, a series of reactive radicals are formed, as
shown.
Besides the above (O2, H2O2, OH-), the other free
radicals and reactive oxygen species ofbiological
importance include singlet oxygen (1O2), hydroperoxy
radical (HOO-), lipidperoxide radical (ROO-), nitric
oxide (NO-) and peroxynit rite (ONOO-).

3. • FORMATION – PHOTOLYSIS, THERMOLYSIS, REDOX REACTIONS
Lipid peroxidation is a source of free radicals
Peroxidation (auto-oxidation) of lipids exposed to oxygen is responsible not
only for deterioration of foods (rancidity) but also for damage to tissues in
vivo, where it may be cause of cancer, inflammatory diseases,
atherosclerosis, and aging. The deleterious effects are considered to be
caused by free radicals (ROO•, RO•, OH•) produced during peroxide
formation from fatty acids containing methylene-interrupted double bonds,
ie, those found in the naturally occurring polyunsaturated fatty acids.
Lipid peroxidation is a chain reaction providing a continuous supply of free
radicals
that initiate further peroxidation.

4. Since the molecular precursor for the
initiation process is generally the
hydroperoxideproduct ROOH, lipid
peroxidation is a chain reaction with
potentially devastating effects. To
control and reduce lipid peroxidation,
both humans in their activities and
nature invoke the use of antioxidants.
Propyl gallate, butylated
hydroxyanisole (BHA),
and butylated hydroxytoluene (BHT)
are antioxidants used as food
additives. Naturally

5. occurring antioxidants include vitamin E (tocopherol), which is lipid-soluble,
and urateand vitamin C, which are water-soluble.
Beta-carotene is an antioxidant at low PO2. Antioxidants fall into two
classes:
(1) preventive antioxidants, which reduce the rate of chain initiation; and
(2) chain-breaking antioxidants, which interfere with chain propagation.
Preventive antioxidants include catalase and other peroxidases that react
with ROOH and chelators of metal ions such as EDTA
(ethylenediaminetetraacetate) and DTPA (diethylenetriaminepentaacetate).
In vivo, the principal chainbreaking antioxidants are superoxide dismutase,
which acts in the aqueous phase to trap superoxide free radicals (O2 −•);
perhaps urate; and vitamin E, which acts in the lipid phase to trap ROO•
radicals.
Peroxidation is also catalyzed in vivo by heme compounds and by
lipoxygenases found in platelets and leukocytes. Other products of auto-
oxidation or enzymic oxidation of physiologic significance include oxysterols
(formed from cholesterol) and isoprostanes(prostanoids).

6. RADICAL REACTIONS WITH BIOMOLECULES.
EFFECT OF FREE RADICALS ON PROTEINS, LIPIDS AND NUCLEIC ACIDS
Free radicals are highly reactive, and are capable of damaging almost all types of
biomolecules (proteins, lipids, carbohydrates, nucleic acids). The fact is that free
radicals beget free radicals i.e. generate free radicals from normal compounds
which
continues as a chain reaction.
Proteins: Free radicals cause oxidation of sulfhydryl groups, and modification of
certain
amino acids (e.g. methionine, cysteine, histidine, tryptophan, tyrosine). ROS may
damage proteins by fragmentation; cross-linking and aggregation.The net result
is that
free radicals mav often result in the loss of biological activity of proteins.
Lipids: Polyunsaturated fatty acids (PUFA) are highly susceptible to damage by
free
radicals. Details have been given under lipid peroxidation.
Carbohydrates: At physiological pH, oxidation of monosaccharides (e.g. glucose)
can
produce H2O2 and oxoaldehydes. It appears that the linkage of carbohydrates to
proteins (glycation) increases the susceptibility of proteins to the attack by free
radicals.
This character assumes significance in diabetes mellitus where protein glycation
is
associated with health complications he. Diabetes Microangiopathy