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Fundamentals > Free Radicals > Flashcards

Free Radicals Flashcards

1
Q

4 types of free radical reactions

A

Hydrogen abstraction
Addition
Termination
Disproportionation

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2
Q

How are ROS produced endogenously (5)

A 
Respiratory chain
Immune system activity 
Cytochrome P450s
Auto-oxidation of biomolecules 
Enzymes with free radicals as intermediates
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3
Q

Exogenous ROS production (5)

A 
UV radiation 
Environmental pollutants 
Tobacco smoke 
Pesticides 
Drugs
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4
Q

Why are most radicals called ROS?

A

As they are derived from oxygen

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5
Q

Respiratory chain and ROS (3)

A

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

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6
Q

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

A

Complex I
Ubiquinone-complex III
Complex IV

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7
Q

Define free radicals (2)

A

Unstable molecules with unpaired electrons

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

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8
Q

Examples ROS free radicals (6)

A 
Superoxide 
Hydroxyl 
Hydroperoxyl 
Peroxyl 
Carbonate 
Carbon dioxide
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9
Q

Examples of ROS non-radicals (5)

A 
Hydrogen peroxide 
Ozone 
Peroxynitrite 
Peroxynitrous acid
Organic peroxides
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10
Q

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

A

Superoxide

Hydrogen peroxide

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11
Q

Which macronutrient is most vulnerable for ROS mediated injury?

A

Lipids

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12
Q

Why are PUFA attractive targets for ROS?

A

Electron density of double bonds

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13
Q

Effects of lipid peroxidation

A

Damage to cell and organelle membranes

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14
Q

Effects of ROS on protein (4)

A 
Changes in :
3D protein structure 
Enzyme active sites 
Receptor binding sites 
Transport functions
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15
Q

ROS injury on nucleic acids (DNA) (3)

A

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

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16
Q

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

A

Mutation

This is the molecular basis of cancer

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17
Q

What causes oxygen toxicity?(3)

A

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

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18
Q

What are antioxidants?

A

Molecules which produce termination reactions with free radicals

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19
Q

3 classes of antioxidants

A

Scavenging antioxidants
Antioxidant enzymes
Proteins with non-enzymatic AOX properties

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20
Q

What scavenging antioxidants?(3)

A

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

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21
Q

Where are scavenging antioxidants located?(2)

A

Biological fluids

Cells and organelle membranes

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22
Q

Water soluble scavenging antioxidants (2)

A

Ascorbic acid

Uric acid

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23
Q

Fat soluble antioxidants (5)

A 
Carotenoids 
Tocopherols
Polyphenols
Flavonoids 
Anthocyanins
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24
Q

Which type of scavenging antioxidants is more important in health?

A

Fat soluble

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25
Q

Where are fat soluble antioxidants found?(3)

A

Membranes
Lipoproteins in circulation
Adipose tissue

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26
Q

Which type of scavenging antioxidant can be stored?

A

Fat soluble

27
Q

How is uric acid formed?

A

From the metabolism of purine

28
Q

Consequences of high levels of uric acid?(2)

A

Gout

Kidney stones

29
Q

Examples of polyphenols (2)

A

Tannins

Gallic acid

30
Q

Examples of flavonoids (2)

A

Catechins

Resveratrol

31
Q

What are antioxidant enzymes?

A

Enzymes which exist to remove ROS

32
Q

What do most antioxidant enzymes have at catalytic centre?

A

Metal ions

33
Q

Metals associated with antioxidant enzymes (4)

A

Copper
Zinc
Manganese
Selenium

34
Q

What happens to the majority of DNA damage

A

It is repaired

35
Q

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

A

Mutation

This is the molecular basis of cancer

36
Q

Examples of antioxidant enzymes (2)

A

Superoxide dismutase

Catalase

37
Q

The role of superoxide dismutase (2)

A

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

38
Q

Isoforms of superoxide dismutase (3)

A

Copper
Zinc
Manganese

39
Q

Role of catalase

A

Converts hydrogen peroxide to water and oxygen

40
Q

Where is catalase located?

A

Peroxisomes

41
Q

What is glutathione?

A

Tripeptide

42
Q

Which AAs does glutathione consist of?

A

Glutamate
Glycine
Cysteine

43
Q

Explain the glutathione system (4)

A

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
Q

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

A

Abundant

60%

45
Q

Where is albumin produced?

A

Liver

46
Q

How does albumin reduce oxidation?

A

It contains several AAs that can react with free radicals

47
Q

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

A

Iron

Copper

48
Q

How can free radical generation of free irons be prevented?

A

Binding to protein

49
Q

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

A

Ferritin
Lactoferrin
Transferrin
Ceruloplasmin

50
Q

What are the two forms of periodontal disease?

A 
Gingivitis (50% of population)
Destructive periodontitis (10-15% of population)
51
Q

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

A

Increases:
Leukocytes
Clotting factors
Pro-inflammatory cytokines

52
Q

What is periodontal disease initiated by?

A

Bacteria

53
Q

Salivary antioxidants (3)

A

Uric acid
Ascorbic acid
Albumin

54
Q

Gingival crevicular fluid antioxidant

A

Glutathione

55
Q

The immune system and ROS (4)

A

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
Q

How are free radical detected?

A

Through their effects in biological systems

57
Q

ROS injury on proteins (3)

A

Causes proteins to:

Cross-link
Aggregate
Fragment

58
Q

Examples of AAs targets for free radical attack (4)

A

Cysteine
Methionine
Phenylalanine
Tyrosine

59
Q

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

A

Cancer
CHD
COPD
Type 1 diabetes

60
Q

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

A

Periodontitis
Ageing
Neurodegeneration

61
Q

Potential negative effects of antioxidant supplements (5)

A

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
Q

What can the immune system use free radicals for?

A

Destroy pathogens

63
Q

Immune system produces free radicals via ______ _____

A

Respiratory burst

Fundamentals (17 decks)

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