LICEO DE CAGAYAN UNIVERSITY

COLLEGE OF MEDICINE
BIOCHEMISTRY 4TH BIMONTHLY

NAME: HAMIDA G. MAROHOM DATE SUMITTED: APRIL 12,2020

FREE RADICALS AND ANTIOXIDANT NUTRIENTS

LEARNING OBJECTIVES:

1. Define the following:

 1.1.Free radicals

 Formed in the body under normal conditions and highly reactive molecular species with an
unpaired electron. They cause damage to nucleic acids, proteins, and lipids in cell
membranes and plasma lipoproteins. This can cause cancer, atherosclerosis and coronary
artery disease, and autoimmune diseases.

 1.2.antioxidants

 Compounds that inhibit oxidation. Oxidation is a chemical reaction that can produce free

radicals, thereby leading to chain reactions that may damage the cells of organisms.
Antioxidants such as thiols or ascorbic acid (vitamin C) terminate these chain reactions. To
balance the oxidative stress, plants and animals maintain complex systems of overlapping
antioxidants, such as glutathione and enzymes example catalase and superoxide dismutase
are produced internally, or the dietary antioxidants vitamin C and vitamin E.

2. Identify and give the biomedical importance of free radicals and antioxidants.

i. They cause damage to nucleic acids, proteins, and lipids in cell membranes and plasma
lipoproteins. This can cause cancer, atherosclerosis and coronary artery disease, and
autoimmune diseases.
ii. Epidemiological and laboratory studies have identified a number of protective antioxidant
nutrients: selenium, vitamins C and E, β-carotene, and other carotenoids, and a variety of
polyphenolic compounds derived from plant foods.

3. Describe the damage caused to DNA, lipids, and proteins by free radicals.

 Interaction of radicals with bases in DNA can lead to chemical changes that, if not repaired
may be inherited in daughter cells. Radical damage to unsaturated fatty acids in cell
membranes and plasma lipoproteins leads to the formation of lipid peroxides, then highly
reactive dialdehydes that can chemically modify proteins and nucleic acid bases. Proteins are
also subject to direct chemical modification by interaction with radicals. Oxidative damage to
tyrosine residues in proteins can lead to the formation of dihydroxyphenylalanine that can
undergo nonenzymic reactions leading to further formation of oxygen radicals.

4. Identify and describe the diseases associated with radical damage.

i. Cancer
ii. Autoimmune Disease
iii. Atherosclerosis
 5. Describe the main sources of oxygen radicals in the body.

 Oxygen radicals arise as a result of the following:

i. Exposure to ionizing radiation such as X-rays and UV rays that can lyse water, leading to
the formation of hydroxyl radicals.

ii. Nonenzymic reactions of transition metal ions including Cu+, Co2+, Ni2+, and Fe2+ can
react nonenzymatically with oxygen or hydrogen peroxide, again leading to the formation
of hydroxyl radicals.

iii. Nitric oxide (an important compound in cell signaling, originally described as the
endothelium-derived relaxation factor) is itself a radical, and, more importantly, can react
with superoxide to yield per-oxy-nitrite, which decays to form hydroxyl radicals.

iv. The respiratory burst of activated macrophages increases the utilization of glucose via
the pentose phosphate pathway to reduce NADP+ to NADPH, and utilization of oxygen to
oxidize NADPH to produce oxygen radicals as cytotoxic agents to kill phagocytosed
microorganisms. The respiratory burst oxidase (NADPH oxidase) is a flavoprotein that
reduces oxygen to superoxide.

v. The normal oxidation of reduced flavin coenzymes. Flavin semiquinone radical will bound
to protein and forms a oxygen radicals this considered as leakage of radicals. Instead of
undergoing complete reduction to water, daily consumption of this will results to daily
production of reactive oxygen species.

6. Describe the mechanisms and dietary factors that protect against radical damage.

 Ascorbate, uric acid and a variety of polyphenols derived from plant foods act as water-
soluble radical trapping antioxidants, forming relatively stable radicals that persist long
enough to undergo reaction to nonradical products. Ubiquinone and carotenes similarly act as
lipid-soluble radical-trapping anti- oxidants in membranes and plasma lipoproteins.

7. Explain how antioxidants can also act as pro-oxidants.

 Prooxidant refers to any endobiotic or xenobiotic that induces oxidative stress either by
generation of ROS or by inhibiting antioxidant systems. It can include all reactive, free radical
containing molecules in cells or tissues. Some of the popular and well known antioxidant
flavonoids have been reported to act as prooxidant also when a transition metal is available.
Other antioxidant can also convert to pro-oxidant such as vitamin C when it is in highest
concentrations.

8. Identify intervention trials of antioxidant nutrients have generally yielded

disappointing results.

 A considerable body of epidemiological evidence suggests that carotene is protective against

lung and other cancers. However, two major intervention trials in the 1990s showed an
increase in death from lung (and other) cancer among people given supplements of β-
carotene. The problem is that although β-carotene is indeed a radical-trapping antioxidant
under conditions of low partial pressure of oxygen, as in most tissues, at high partial
pressures of oxygen (as in the lungs) and especially in high concentrations, β-carotene is an
auto- catalytic pro-oxidant, and hence can initiate radical damage to lipids and proteins.

REFERENCE: HARPER’S ILLUSTRATED BIOCHEMISTRY 31ST EDITION