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Flashcards in Free Radicals Deck (63):
1

4 types of free radical reactions

Hydrogen abstraction
Addition
Termination
Disproportionation

2

How are ROS produced endogenously (5)

Respiratory chain
Immune system activity
Cytochrome P450s
Auto-oxidation of biomolecules
Enzymes with free radicals as intermediates

3

Exogenous ROS production (5)

UV radiation
Environmental pollutants
Tobacco smoke
Pesticides
Drugs

4

Why are most radicals called ROS?

As they are derived from oxygen

5

Respiratory chain and ROS (3)

Most of oxygen uptake is utilised by ETC
oxidation of nutrients feeds electrons into chain
Leakage of free radicals is a by-product if this process

6

Name the key points of leakage in the ETC (3)

Complex I
Ubiquinone-complex III
Complex IV

7

Define free radicals (2)

Unstable molecules with unpaired electrons
Free radicals are highly reactive and will react with other molecules in order to stabilise them

8

Examples ROS free radicals (6)

Superoxide
Hydroxyl
Hydroperoxyl
Peroxyl
Carbonate
Carbon dioxide

9

Examples of ROS non-radicals (5)

Hydrogen peroxide
Ozone
Peroxynitrite
Peroxynitrous acid
Organic peroxides

10

Mitochondria is the richest sources of which ROS?(2)

Superoxide
Hydrogen peroxide

11

Which macronutrient is most vulnerable for ROS mediated injury?

Lipids

12

Why are PUFA attractive targets for ROS?

Electron density of double bonds

13

Effects of lipid peroxidation

Damage to cell and organelle membranes

14

Effects of ROS on protein (4)

Changes in :
3D protein structure
Enzyme active sites
Receptor binding sites
Transport functions

15

ROS injury on nucleic acids (DNA) (3)

May cause strand scission
This is cleaving of sugar-phosphate backbone
May alter bases

16

What can un-repaired DNA damage lead to (2)

Mutation
This is the molecular basis of cancer

17

What causes oxygen toxicity?(3)

The formation of ROS
Through endogenous processes
Additional environmental burden increases exposure

18

What are antioxidants?

Molecules which produce termination reactions with free radicals

19

3 classes of antioxidants

Scavenging antioxidants
Antioxidant enzymes
Proteins with non-enzymatic AOX properties

20

What scavenging antioxidants?(3)

Molecules which react with ROS to form stable products
They end chain reaction in biological systems
They are converted to non-AOX species

21

Where are scavenging antioxidants located?(2)

Biological fluids
Cells and organelle membranes

22

Water soluble scavenging antioxidants (2)

Ascorbic acid
Uric acid

23

Fat soluble antioxidants (5)

Carotenoids
Tocopherols
Polyphenols
Flavonoids
Anthocyanins

24

Which type of scavenging antioxidants is more important in health?

Fat soluble

25

Where are fat soluble antioxidants found?(3)

Membranes
Lipoproteins in circulation
Adipose tissue

26

Which type of scavenging antioxidant can be stored?

Fat soluble

27

How is uric acid formed?

From the metabolism of purine

28

Consequences of high levels of uric acid?(2)

Gout
Kidney stones

29

Examples of polyphenols (2)

Tannins
Gallic acid

30

Examples of flavonoids (2)

Catechins
Resveratrol

31

What are antioxidant enzymes?

Enzymes which exist to remove ROS

32

What do most antioxidant enzymes have at catalytic centre?

Metal ions

33

Metals associated with antioxidant enzymes (4)

Copper
Zinc
Manganese
Selenium

34

What happens to the majority of DNA damage

It is repaired

35

What can un-repaired DNA damage lead to (2)

Mutation
This is the molecular basis of cancer

36

Examples of antioxidant enzymes (2)

Superoxide dismutase
Catalase

37

The role of superoxide dismutase (2)

Catalyses the conversion of superoxide radials to hydrogen peroxide
Critical in quenching ROS formed in respiration

38

Isoforms of superoxide dismutase (3)

Copper
Zinc
Manganese

39

Role of catalase

Converts hydrogen peroxide to water and oxygen

40

Where is catalase located?

Peroxisomes

41

What is glutathione?

Tripeptide

42

Which AAs does glutathione consist of?

Glutamate
Glycine
Cysteine

43

Explain the glutathione system (4)

Reduced glutathione (GSH) is the substrate for glutathione peroxidase
GPx uses selenium to reduce hydrogen peroxide
GSH is oxidised in process to oxidised glutathione
Which can be regenerated by glutathione reductase

44

Albumin is the most _____ blood plasma protein. It accounts for ____ of protein in circulation

Abundant
60%

45

Where is albumin produced?

Liver

46

How does albumin reduce oxidation?

It contains several AAs that can react with free radicals

47

Free forms of which metals can cause free radical generation?(2)

Iron
Copper

48

How can free radical generation of free irons be prevented?

Binding to protein

49

Which proteins can free irons bind to in order to prevent free radical generation?(4)

Ferritin
Lactoferrin
Transferrin
Ceruloplasmin

50

What are the two forms of periodontal disease?

Gingivitis (50% of population)
Destructive periodontitis (10-15% of population)

51

How does periodontitis increase risk factors for CVD?(3)

Increases:
Leukocytes
Clotting factors
Pro-inflammatory cytokines

52

What is periodontal disease initiated by?

Bacteria

53

Salivary antioxidants (3)

Uric acid
Ascorbic acid
Albumin

54

Gingival crevicular fluid antioxidant

Glutathione

55

The immune system and ROS (4)

Respiratory burst involves greater oxygen uptake by cell
And faster glucose utilisation to generate NADPH

NAPDH oxidase generates superoxide
Which breaks down to form longer-acting oxidants

56

How are free radical detected?

Through their effects in biological systems

57

ROS injury on proteins (3)

Causes proteins to:

Cross-link
Aggregate
Fragment

58

Examples of AAs targets for free radical attack (4)

Cysteine
Methionine
Phenylalanine
Tyrosine

59

Conditions where ROS plays a major role in disease (4)

Cancer
CHD
COPD
Type 1 diabetes

60

Conditions where ROS contributes to the progression of condition (3)

Periodontitis
Ageing
Neurodegeneration

61

Potential negative effects of antioxidant supplements (5)

High dose may be excreted with no benefit
High dose may lead to pro-oxidant effect
Metabolism of the antioxidant may prevent benefit
Supplementation dose may not reach target tissue
High concentrations may enhance disease progression through non-ROS related mechanisms

62

What can the immune system use free radicals for?

Destroy pathogens

63

Immune system produces free radicals via ______ _____

Respiratory burst