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ESA2 - Metabolism, Endocrinology and Haematology > Oxidative Stress > Flashcards

Oxidative Stress Flashcards

1
Q

What is a free radical?

A

An atom or molecule that contained one or more unpaired electrons and is capable of independent existence

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2
Q

True or False:

Reaction of a radical with a molecule usually just affects that molecule only.

A

False

Reaction of a radical with a molecule typically generates a second radical thereby propgating damage - sets off a chain reaction

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3
Q

What are some common reactive oxygen species?

A

Superoxide, hydrogen peroxide, hydroxyl radical

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4
Q

What are some common reactive nitrogen species?

A

Nitric oxide, peroxygnitrite

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5
Q

What is produced when superoxide reacts with nitric oxide?

A

Peroxygnitrite (ONOO-)

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6
Q

How is superoxide produced?

A

By adding an electron to molecular oxygen

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7
Q

Why is hydrogen peroxide dangerous if it is not itself a free radical?

A

It can react eg with Fe2+ to produce free radicals and is readily diffusible

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8
Q

What is the most reactive and damaging free radical?

A

Hydroxyl radical

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9
Q

What are the two main types of damage to DNA caused by ROS?

A

1) ROS reacts with base, leading to mispairing and mutation

2) ROS reacts with sugar, causing strand break and mutation on repair

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10
Q

What can be used as measurement of oxidative damage?

A

Amount of 8-oxo-dG present in cells

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11
Q

How can ROS damage proteins?

A

1) Modification of side chains, eg introduction of disulphide bonds
2) Reacting with backbone - fragmentation of protein leading to protein degradation

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12
Q

How can the modification of amino acid side chains by ROS cause damage?

A

Cause change in protein structure leading to loss/gain of function

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13
Q

What is the role of disulphide bonds?

A

Folding and stability of some proteins

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14
Q

What are disulphide bonds formed between?

A

Thiol groups of cysteine residues

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15
Q

How can inappropriate disulphide bond formation occur as a result of ROS damage?

A

If ROS takes electrons from cysteines causing misfoldng, crosslinking and disruption of function

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16
Q

How can ROS cause damage to lipids?

A

Free radical extracts H from a polyunsaturated fatty acid in membrane lipid,

Lipid radical forms which can react with oxygen to form a lipid peroxyl radical,

Chain reaction formed as lipid peroxyl radical extracts hydrogen from nearby fatty acid,

Hydrophobic environment of bilayer disrupted and membrane integrity fails

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17
Q

What are some endogenous sources of biological oxidants?

A

Electron transport chain, nitric oxide synthases, NADPH oxidases, peroxidases, lipooxygenases

18
Q

What are some exogenous sources of biological oxidants?

A

Radiation (cosmic, UV light, X-rays), pollutants, drugs (eg primaquine - an anti-malarial), toxins (paraquat - herbicide)

19
Q

How can the electron transport chain sometimes produce free radicals?

A

Occasionally electrons can accidentally escape chain and react with dissolved oxygen to form superoxide

20
Q

What does nitric oxide usually do?

A

Signalling molecule

Activates guanylyl cyclase which produce cGMP which activates protein kinase G

21
Q

What are the 3 types of nitric oxide synthase?

A

Inducible nitric oxide synthase
Endothelial nitric oxide synthase
Neuronal nitric oxide synthase

22
Q

What is respiratory burst?

A

Rapid release of superoxide and hydrogen peroxide from phagocytic cells (eg neutrophils) - part of antimicrobial defence system

23
Q

What is chronic granulomatous disease?

A

Genetic defect in NADPH oxidase complex causing enhanced susceptibility to bacterial infections

24
Q

What does speroxide dismutase do?

A

Converts superoxide to hydrogen peroxide and oxygen

25
Q

What does catalase do?

A

Converts hydrogen peroxide into water

26
Q

What is glutathione?

A

Tripeptide syntehsised by body to protect against oxidative damage

27
Q

How does glutathione protect against oxidative damage?

A

Thiol group of Cysteine donates e- to ROS. GSH (reduced form) then reacts with another GSH to form disulphide (GSSG)

28
Q

What does glutathione peroxidase require as a cofactor?

A

Selenium

29
Q

What enzyme reduces GSSG back to GSH?

A

Glutathione reductase - catalyses the transfer of electrons from NADPH to disulphide bond

30
Q

True or False:

NADPH from pentose phosphate pathway is not essential for protection against free radical damage

A

False!

It is essential for regeneration of GSH

31
Q

What are the free radical scavengers?

A

Vitamin E and Vitamin C

also carotenoids, flavonoids, uric acid, melatonin

32
Q

Is vitamin E lipid soluble or water soluble?

A

Lipid soluble so important for protection against lipid peroxidation

33
Q

Is vitamin C lipid soluble or water soluble?

A

Water soluble so important in regenerating reduced form of vitamin E

34
Q

How do free radical scavengers reduce free radical damage?

A

By donating hydrogen atom (and its electron) to free radicals in a nonenzymatic reaction

35
Q

What is galactosaemia?

A

High levels of galactose in blood

36
Q

What 3 enzymes are involved in metabolism of galactose?

A

Galactokinase, uridyl transferase and UDP galactose epimerase (deficiency in any of these leads to galactosaemia)

37
Q

What causes cataracts?

A

1) Build up of galacitol
2) Increased activity of aldose reductase consumes excess NADPH, compromised defences against ROS damage, crystallin protein in lens of the eye is denatured

38
Q

What is the antidote to paracetamol overdose and how does it work?

A

Acetylcysteine - works by replenishing glutathione levels

39
Q

What toxic metabolite accumulates with high levels of paracetamol?

A

NAPQI

40
Q

What are Heinz bodies?

A

Inclusions within red blood cells composed of denatured hemoglobin.

41
Q

Which fat soluble vitamin plays an important role in protecting cells against oxidative damage by acting as a free radical scavenger?

A

Vitamin E plays an important role in protecting cells against lipid peroxidation. Vitamin C (Ascorbic acid) is a water soluble antioxidant that plays an important role in regenerating the reduced form of Vitamin E.

ESA2 - Metabolism, Endocrinology and Haematology (19 decks)

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