1. Lipid Peroxidation

5. Introduction
Oxidative deterioration of lipids containing any number of carbon-carbon double bonds
Fatty acids
Cholesterol
The deleterious effects are considered to be caused by FREE RADICALS produced during peroxide formation from fatty acids containing double bonds, ie, those found in the naturally occurring polyunsaturated fatty acids

6. Free radicals A free radical is any species capable of independent
existence that contains one or more UNPAIRED ELECTRONS
● designation: R●
● to be paramagnetic
● renowned for their high chemical reactivity
Forming: X − e X●+ (oxidation)

7. Free radical reactions
Free radicals easily react with a biological molecules (mainly
non-radicals) generating new radicals – initiate chain reactions
Types of radical reaction:
○ reactions between two radicals (NO●− + O2●− ONOO−)
○ radical addition on to another molecule
(addition of OH● to guanine in DNA)
○ oxidation and reduction of non-radicals
○ abstraction of a hydrogen atom from C–H bond (fatty acids)

8. 1. Mitochondria
Mitochondrial electron transport chain complexes I, II and III take part in O2●− production
Importance of coenzyme Q semiquinone radical! O2 O2
O2●−
O2●− O2
O2●−

9. Mitochondria ● one of the most important sources of ROS production
● complexes of ETC can catalyse one electron reduction of O2
to superoxide
● cytochrome c oxidase produces radical intermediates, although
they are firmly bound to the enzyme
● NADH dehydrogenase (complex I) and cytochrome bc1
(complex III) are major sites of superoxide production
● electron carrier coenzyme Q (ubiquinone) is during electron
transport oxidized and afterwards reduced by single electron
forming radical intermediate (semiquinone) and it can react with
O2 to give superoxide O2●−

10. Free radical sources Exogenous Endogenous Foods Air pollutants
Radiation
Endogenous
Metabolism (mitochondria and peroxisomes)
Detoxification – cytochrome P450
Immune cells

11. Production of toxic compounds
Many secondary by-products of lipid oxidation are potential carcinogens
Hydroperoxides are known to damage DNA
Carbonyl compounds may affect cellular signal transduction
Aldehydes: 4-hydroxynonenal, and MDA
Epoxides and hydrogen peroxide by-products are known carcinogens

12. Mechanisms to induce lipid peroxidation
Photoxidation
Singlet oxygen is involved
Require sensitizers: porphyrins, myoglobin, riboflavin, bilirubin.
Enzymatic Oxidation
Cyclooxygenase and lipoxygenase catalyze the reactions between oxygen and polyunsaturated fatty acids
Autoxidation
Free Radical Chain-reaction

13. Reactive Oxygen Species and Free Radicals
Triplet oxygen
Superoxide
Singlet Oxygen
Hydroperoxyl radical
Hydroxyl radical
Hydrogen peroxide
Ozone
Peroxyl radical (ROO.)
Alkoxyl radical (RO.)
Iron-oxygen complexes (ferryl and perferryl radicals)
Thiyl radicals (RS.)
Nitric oxide (.NO)

15. Implications of Lipid Oxidation to Human Health

16. Oxidative Stress

17. Consequences of Lipid Peroxidation
Structural changes in membranes
Alter fluidity and ion channels
Alter membrane-bound signaling proteins
Increase membrane permeability
Form lipid oxidation products adducts/crosslinks with non lipids
e.g., proteins and DNA
Cause direct toxicity
e.g., 4-hydroxynonenal, MDA
DNA damage and mutagenesis

18. Pathological Conditions that Involve Oxidative Stress
Inflammation
Atherosclerosis
Ischemia/reperfusion injury
Cancer
Aging

19. Inflammation

20. ROS (reactive oxygen species) and atherosclerosis

21. Aging
The process(es) that occur during life which culminate in changes that decrease an individual’s ability to handle biological challenges

22. Free radicals and Aging
Protein cross-linking
Wrinkles in skin
Reduces flexibility in arterial cells
Hampers the functions of proteins and enzymes
Impedes message transmission between nerve cells in the brain
Damage DNA and RNA molecules
Results in impaired DNA replication and protein assembly
Causes chronic degenerative diseases and cancer
Protein degradation

23. Antioxidative defense
An antioxidant is any substance that delays, prevents or removes oxidative damage to a target molecule
There is no universal best antioxidant!
Their relative importance depends upon:
Which, how, where ROS is generated and what target of damage is measured

24. Antioxidants
Antioxidants function by interfering with the chain reaction. If the number of free radicals can be kept low enough, oxidation will not occur. The following is a model for the type of compound that can function effectively as an antioxidant:

25. Main mechanisms for inhibition of oxidative reactions
1. Interrupt the free-radical chain mechanism
2. Function as being preferentially oxidized - poor protection
3. Reducing agents
4. Chelating agents for free iron

26. Ideal Antioxidants No harmful physiological effects
Not contribute an objectionable flavor, odor, or color to the product
Effective in low concentration
Fat soluble
Carry-through effect – no destruction during processing
Readily available
Economical
Non-absorbable by the body

27. Antioxidant Defenses in Biological Systems
Fat-soluble cellular membrane consists
Vitamin E
beta-carotene
Coenzyme Q (10)
Water soluble antioxidant scavengers
Vitamin C
Glutathione peroxidase,
Superoxide dismutase
Catalase

28. Thank you for attention!