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MEH > Oxidative stress > Flashcards

Oxidative stress Flashcards

1
Q

What is a ROS?

A

Reactive Oxygen Species

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2
Q

What is a RNS?

A

Reactive Nitrogen Species

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3
Q

What is a free radical?

A

A species with an unpaired electron

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4
Q

How is a free radical denoted?

A

Using a superscript dot

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5
Q

How are ROS produced?

A

O2 gains an electron forming Superoxide (O2•–)

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6
Q

What happens to Superoxide?

A

It is a ROS so can cause direct damage
Can react with Nitric oxide to form Peroxynitrite (ONOO-) a powerful oxidant

Or converted into Hydrogen peroxide H2O2 a powerful oxidant

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7
Q

What enzyme converts superoxide into Hydrogen peroxide H2O2?

A

Superoxide dismutase (SOD)

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8
Q

How does Hydrogen peroxide go onto cause damage?

A

Fenton reaction
H2O2 reacts with Fe2+ producing ROS/free radicals

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9
Q

What can H2O2 by reduced to to cause damage?

A

Water and Hydroxyl radical OH .

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10
Q

What 2 ways can ROS/RNS damage DNA?

A

ROS reacts with base (takes e-) changing the base leading to misplacing and mutation

ROS reacts with sugar (causes strand break and mutation on repair).

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11
Q

What can the mutation on repair of DNA caused by ROS/RNS damage lead to?

A

Cancer

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12
Q

What 2 ways can ROS damage proteins?

A

Damage the:
-Backbone
-Sidechains

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13
Q

How does ROS interacting with the protein back bone cause problems?

A

Leads to backbone fragmenting
Leads to protein degradation

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14
Q

How does ROS reacting with the amino acid side chains of a protein cause problems?

A

Modifies the amino acid and it’s properties
Can lead to the inappropriate formation of disulphide bonds (between thiol groups) thus changing the structure of the proteins at the secondary level

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15
Q

How can changing the protein structure affect a protein?

A

Lead to loss of function
Degradation
Or gain of function

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16
Q

How do inappropriate disulphide bonds form when a ROS reacts with a protein?

A

ROS takes electrons from cysteines
Causes misfolding, cross linking and disruption of function

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17
Q

How do ROS cause damage to lipids?
(General process)

A

Free radical reacts with polyunsaturated fatty acid removing a H
Lipid radical forms
Lipid radical reacts with oxygen forming lipid peroxyl radical
CHAIN REACTION OCCURS
Lipid peroxyl radical reacts with a polyunsaturated fatty acid removing H ETC….

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18
Q

Why are ROS dangerous to cellular membranes?

A

The hydrophobic environment of the bilayer gets disrupted by Lipid peroxidation and membrane integrity fails

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19
Q

What is Lipid peroxidation?

A

The chain reaction caused by the damage of free radical/ROS to lipids of the cell membrane

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20
Q

What are the 2 types of sources of oxidants?

A

Endogenous
Exogenous

21
Q

List 3 main examples of endogenous oxidants

A

Electron transport chain
Nitric oxide synthases
NADPH oxidases

22
Q

List 4 examples of Exogenous oxidants

A

Radiation (UV, X-rays and cosmic rays)
Pollutants
Drugs (primaquine =anti malarial)
Toxins (herbicides)

23
Q

How is the Electron Transport chain a source of ROS?

A

Electrons sometimes escape and react with dissolved O2 forming Superoxide

24
Q

What is Respiratory burst?

A

The rapid production of Superoxide and H2O2 from Phagocytes to destroy invading bacteria

25
Q

Which enzyme provides the electron to oxygen to form superoxide in phagocytes?

A

NADPH Oxidase

26
Q

What is Chronic granulomatous disease?

A

Genetic defect in NADPH oxidase

27
Q

Why does Chronic granulomatous disease cause increased susceptibility to bacterial infections?

A

Superoxide can’t be produced by phagocyte so respiratory burst will not occur to destroy bacteria

28
Q

What are the 2 key enzymes that are important in the cellular defences against ROS?

A

Superoxide dismutase (SOD)
Catalase

29
Q

What is the role of Superoxide dismutase in cellular defences against ROS?

A

Converts Superoxide to H2O2 and oxygen
Superoxide is very good at initiating chain reactions

30
Q

What is the role of catalase in the cellular defences against ROS?

A

Converts H2O2 to water and oxygen

31
Q

What is GSH?

A

The reduced/active form of Glutathione

32
Q

How does GSH protect from oxidative stress/ROS?

A

Electron from thiol group of cysteine in GSH is donated to the ROS
This causes GSH to form a disulphide bond with another GSH forming GSSG

33
Q

What is GSSG?

A

The oxidised/inactive form of Glutathione

34
Q

How is GSSG recycled back into the active reduced form of Glutathione (GSH)?

A

NADPH transfers electron to disulphide bond
GSH reforms

35
Q

Which pathway is a major source of NADPH?

A

Pentose Phosphate pathway

36
Q

What is the significance of Vitamin E and Vitamin C in cellular defences against free radicals?

A

Vitamin E protects against lipid peroxidation
Vitamin C regenerates reduced/active form of Vitamin E

37
Q

What is oxidative stress?

A

The imbalance in Oxidants and defences/antioxidants

38
Q

How does cataracts form occur as a result of oxidative stress in Galactosaemia?

A

Galactose accumulates , enters ALDOSE reductase pathway depleting NADPH forming galactitiol
Depleted NADPH means Glutathione can’t be converted back to its active reduced form
Damage as a result of ROS occurs in eye
Inappropriate disulphide bonds in crystallin protein in eye form causing protein getting denatured

39
Q

Why are individuals with G6PDH (Glucose 6 phosphate dehydrogenase) Deficiency susceptible to oxidative damage?

A

Pentose phosphate pathway ceases
Major source of NADPH
NADPH essential in regenerating GSH

40
Q

What are Heinz bodies?

A

When inappropriate disulphide bonds result in aggregations of cross linked haemoglobin

41
Q

What is a clinical sign of G6PDH deficiency?

A

Heinz bodies

42
Q

Which part of the body removes Heinz bodies?

A

Spleen

43
Q

How are normal levels of paracetamol normally metabolised?

A

Metabolised via pathways producing safe products

44
Q

What is the toxic product produced when somebody overdoses on paracetamol and why is this produced?

A

NAPQI
Made since safe metabolic pathways of paracetamol fully saturated

45
Q

How is NAPQI directly and indirectly toxic?

A

Directly causes oxidative damage to Hepatocyte

Indirectly: Depleted GSH making cell vulnerable to oxidative damage

46
Q

How is an overdose of Paracetamol treated?

A

Drug Acetylcysteine

47
Q

How does Acetylcysteine help treat a Paracetomol overdose?

A

Replenishes GSH (Active Glutathione) to protect against oxidative damage

48
Q

What are the 3 ways by which a cell can be damaged by an oxidant?

A

Lipid peroxidation
Damage to proteins
Damage to DNA

MEH (33 decks)

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