FREE RADICALS &

OXIDATIVE STRESS
LEARNING OBJECTIVES

To define reactive To discuss the To reflect on

oxigen species (ROS) imbalance between consequences related
and oxidative stress. prooxidant and to oxidative stress in
antioxidant systems. patologic conditions.
 Week 7
PRELECTIO QUIZ _BIOCHEM_Free Radicals and
Oxidative Stress

QUIZ Password:
Superoxide
INTRODUCTION
 Oxygen (O2) is essential for the life of aerobic
organisms. 
 Oxygen is relatively inert at body
temperature.
 About 90% of our O2 usage is committed to
oxidative phosphorylation.
 Enzymes that use O2 for hydroxylation and
oxygenation reactions consume another 10%,
and a residual fraction, <1%, is converted
to reactive oxygen species (ROS), such as
superoxide and hydrogen peroxide.
FREE RADICALS
A free radical is any chemical
specie (atom, ion, or molecule)
that has an unpaired electron in an
orbit, in most cases rendering
them highly reactive.

Reactive O2  species

(ROS) are chemically
reactive molecules
containing O2 
 REACTIVE The diradical is the natural, ground-state form
of O2 at body temperature.

OXYGEN SPECIES ROS are partially reduced, reactive forms of

oxygen. 
Free radicals can be formed endogenously in the body or by external stimuli
such as irradiation or chemicals from air pollutants, etc.

Most O2  radicals are generated in the mitochondria by the electron transport

chain.
 FREE RADICALS
Free radicals have important functions in the body:

 Defense against microorganisms: phagocytic cells such as macrophages

and neutrophils use free radicals to destroy infective agents. 

 Signal transduction: free radicals have been shown to act in numerous

signaling pathways such as the nuclear factor-κβ signaling pathways, which are
crucial for immunity, cell development, and growth. 

 Mitogenic effects: gene expression has also been shown to be altered by free
radicals in both a deleterious and desirous manner. 
  Nitric oxide synthases (NOS) catalyze the
production of the free radical nitric oxide (NO •)
from the amino acid L-arginine.

There are three isoforms of NOS:

REACTIVE
NITROGEN  nNOS in neuronal tissue, where NO • serves a
neurotransmitter function;
SPECIES (RNS)  iNOS in the immune system, where it is
involved in regulation of the immune response;
 eNOS in endothelial cells, where NO • , known
as endothelium-derived relaxation factor
(EDRF), has a role in the regulation of vascular
tone.
THE RESPIRATORY
BURST IN
MACROPHAGES
Chronic granulomatous
disease (CGD) is an
inherited disease resulting
from a genetic defect in
NADPH oxidase.

The inability to produce

superoxide leads to
chronic life-threatening
bacterial and fungal
infections.
 ISCHEMIA/REPERFUSION INJURY
 ROS are thought to play a major role in
reperfusion injury. When cells are
deprived of oxygen, they must rely on
anaerobic glycolysis and glycogen stores
for ATP synthesis.

 NADH and lactate accumulate, and all

the components of the mitochondrial
electron transport system are saturated
with electrons because the electrons
cannot be transferred to oxygen. The
mitochondrial membrane potential is
increased (hyperpolarized), and when
oxygen is reintroduced, great quantities
of ROS are rapidly produced.

 ROS flood throughout the cell, damaging

Damage to heart tissue during a myocardial infarction occurs
not during the hypoxic or ischemic phase but during membrane lipids, DNA, and other vital
cellular constituents, leading to necrosis.
reoxygenation of the tissue.
WHAT IS OXIDATIVE
STRESS?
 Increased production
or decreased
scavenging of ROS
may lead to an excess
of free radicals, a
condition called
oxidative stress.
 Commonly measured biomarkers
 Inflammation and oxidative stress are critical to

OXIDATIVE the initiation and progression of

atherosclerosis.

STRESS AND Oxidation of proteins and lipid peroxidation of

membrane polyunsaturated fatty acids in
INFLAMMATION. lipoproteins by reactive oxygen species can
facilitate the development of atherosclerotic
lesions.
 OXIDATIVE STRESS AND
ATHEROSCLEROSIS.
 https://www.youtube.com/watch?v=wbShOXhO6p8

 Atherosclerosis Pathogenesis

TO CHRONIC
INFLAMMATORY
DISEASE
 CLASS ASSIGNMENT
 Workout Groups
 Create a meeting (Professor will join these meetings)
 Discuss & define student roles: seeker, analyzer, writer, figure creator
 Download the Questionnaire avialable at Mis Cursos to work on. You
might use other sources differently from the prelectio articles in order
to answer some of the questions. Remember to cite those references
at the end of the questionnaire
 Upload your questionnaire into Mis Cursos (2:30 CST) and return for
receive feedback.
FEEDBACK
 Free radicals (ROS/RNS) are produced by normal metabolism and are
involved in various physiological and pathological conditions.

 When there is an imbalance between the antioxidants and oxidants, the

fee radicals accumulate leading to vigorous damage to macromolecules
such as nucleic acids, proteins and lipids.

 This leads to tissue damage in various disease conditions such as

diabetes mellitus, neurodegenerative diseases, cancer, cardiovascular
diseases, rheumatoid arthritis, asthma et.
 POSLECTIO ASSIGMENT
 After class, please read the article “Oxidative Stress and
Antioxidants in Atherosclerosis Development and
Treatment” and answer correctly the POSLECTIO Quiz into
MIS CURSOS.