The document discusses oxidative stress and redox regulation. It defines oxidative stress as an imbalance between reactive oxygen species and antioxidants in cells. Reactive oxygen species are formed through normal metabolism but also during environmental stress. They can damage biomolecules and lead to diseases. Antioxidants help neutralize reactive oxygen species and may help prevent certain diseases. Redox regulation involves electron transfer processes like oxidation, which is the loss of electrons, and reduction, which is the gain of electrons. An example of redox regulation is the mitogen-activated protein kinase pathway, which is involved in cell survival signaling and can be activated under oxidative stress conditions through redox modification.

1. Group 1
Hadia Azhar
Amna Hafeez
Muqadas Shehzad
Umm-e-Farwa

2. “Oxidative Stress &
Redox Regulation”

3. Oxidative stress
• “A disturbance in the balance between reactive oxygen
species (ROS) and antioxidants is called oxidative
stress.”
• Under normal conditions, cells are able to balance the
production of oxidants and antioxidants.
• Oxidative stress occurs when there is imbalance in our
cells due to either an increase in free radicals or a
decrease in antioxidants.

4. Reactive Oxygen Species
Reactive oxygen species (ROS) are chemically
reactive chemical species containing oxygen.
Examples:
1. peroxides (H2O2),
2. superoxide (O2-֗),
3. hydroxyl radical ( HO-),
4. singlet oxygen(O2).

5. Generation of ROS
In a biological context, ROS are formed as a natural
byproduct of the normal metabolism of oxygen and
have important roles in cell signaling and
homeostasis.
However, during times of environmental stress
(e.g., UV or heat exposure), ROS levels can increase
dramatically.

6. • The reduction of molecular oxygen (O2) produces
superoxide (•O−2) and is the precursor of most other
reactive oxygen species:
O2 + e− → •O−2
• Dismutation of superoxide produces hydrogen
peroxide (H2O2):
2 H+ + •O−2 + •O−2 → H2O2 + O2
• Hydrogen peroxide in turn may be partially reduced to
hydroxyl radical (•OH) or fully reduced to water:
H2O2 + e− → HO− + •OH
2 H+ + 2 e- + H2O2 → 2 H2O
Generation of ROS

7. Exogenous ROS
Exogenous ROS can be produced from pollutants, tobacco,
smoke, drugs, xenobiotics , or radiation.
• Ionizing radiation can generate damaging intermediates
through the interaction with water, a process termed as
radiolysis.
• In the process, water loses an electron and becomes
highly reactive. Then through a chain reaction, water is
sequentially converted to hydroxyl radical (•OH),
hydrogen peroxide (H2O2), superoxide radical (•O−2)
and ultimately oxygen (O2).
• hydrogen peroxide is actually damaging to DNA.

8. Endogenous ROS
• ROS are produced intracellularly through multiple
mechanisms and depending on the cell and tissue types.
• the major producers of ROS are NADPH oxidase
complexes in cell membranes, mitochondria,
peroxisomes, and endoplasmic reticulum.

9. Damaging effects
Harmful effects of reactive oxygen species on the cell are
most often:
1. damage of DNA or RNA
2. oxidations of polyunsaturated fatty acids in lipids (lipid
peroxidation)
3. oxidations of amino acids in proteins
4. oxidative deactivation of specific enzymes by oxidation
of co-factors

11. Antioxidants
• An antioxidant is a molecule that inhibits the oxidation
of other molecules.
• Oxidation is a chemical reaction that can produce free
radicals (ROS).
• Source:
Most antioxidants are obtained from diet but they
can also be taken as supplements in the form of capsules
or tablets.

12. Endogenous Antioxidants:
• Vitamins ( vit A ,C , E , K)
• Minerals ( zinc, selenium)
• Amin acids ( GSH, methionine, N- acetyl cysteine)
• Enzymes ( co enzyme Q, superoxide dismutase ( SOD),
glutathione peroxidase)

14. Disease prevention:
• Antioxidants may be used in disease prevention but the
extent of their benefits is not fully understood. The use
of antioxidants to treat disease states induced by
oxidative stress is controversial.
• For example, antioxidants may be useful in treating
patients after a stroke to protect the nerves and brain
cells from oxidative damage.
• consumption of food rich in vitamin E may reduce the
risk of coronary heart disease in middle-aged to older
men and women.

15. Diseases caused by Oxidative stress
Damage to biomolecules like lipids , proteins , DNA will
eventually lead to diseases like:
• Cancer
• Diabetes
• Rheumatoid arthritis
• Myocardial infarction
• Cardiovascular diseases
• Chronic inflammation
• Atherosclerosis

16. Redox Regulation

17. • Redox (short for reduction–oxidation reaction) is
a chemical reaction in which the oxidation states of atoms
are changed. Any such reaction involves both a reduction
process and a complementary oxidation process, two key
concepts involved with electron transfer processes.

18. It can be explained in simple terms:
• Oxidation is the loss of electrons or an increase in
oxidation state by a molecule, atom, or ion.
• Reduction is the gain of electrons or a decrease in
oxidation state by a molecule, atom, or ion.

19. EXAMPLE OF REDOX
REGULATION

20. • A good example is the reaction between hydrogen and fluorine in
which hydrogen is being oxidized and fluorine is being reduced:
H2 + F2 → 2 HF
We can write this overall reaction as two half-reactions:
the oxidation reaction:
H2 → 2 H+ + 2 e−
and the reduction reaction:
F2 + 2 e− → 2 F−

21. Redox regulation of
cell survival at the
signal-transduction
level

22. • Mitogen-activated protein kinase
MAPK operates in a cascade fashion with a MAP kinase
kinase kinase (MAPKKK) phosphorylating and activating a
MAP kinase kinase (MAPKK), which then phosphorylates
and activates a MAP kinase (MAPK).
Role of MAPK for cell survival under oxidative stress:
signaling promotes cell survival under mild oxidative stress,
whereas SAPKs seem to induce cell death as a response to
oxidative injuries.

23. b. Redox regulation of MAPK:
• Multiple evidence shows that oxidative stress can activate
the ERK pathway.
• Redox modification can regulate ERK activation at the
level of the tyrosine kinase receptor and the Ras
activation.