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Metabolism > Oxidative Stress > Flashcards

Oxidative Stress Flashcards

1
Q

Define free radicals

A

An atom or molecule that contains one or more unpaired electron and is capable of ‘free’ existence.

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2
Q

Which molecules is the free radical exception?

A

The molecular oxygen that we breathe. Has 2 unpaired electrons but not highly reactive to the same extent.

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3
Q

Name the reactive nitrogen species

A

nitric oxide (NO.) and peroxynitrite (ONOO-)

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4
Q

What is nitric oxide used for?

A

vasodilation and immune response in high concs

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5
Q

What is the most reactive and damaging free radical?

A

Hydroxyl radical (OH.)

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6
Q

Why is hydrogen peroxide dangerous?

A

readily diffusible and can react to produce very damaging free radicals

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7
Q

How can ROS damage DNA?

A

react with base: mispairing and mutation

react with sugar: strand break and mutation on repair

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8
Q

What is 8-oxo-dG used for?

A

Measurement of oxidative damage within the cell

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9
Q

How can ROS damage proteins?

A

damage backbone: fragmentation and degradation

react with side chain: modified amino acids

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10
Q

What can a change in protein structure cause?

A

gain of function, loss of function and degradation

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11
Q

Where do disulfide bonds form?

A

Between thiol groups of cysteine residues

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12
Q

What can inappropriate disulfide bond formation lead to?

A

misfolding, cross-linking, disruption of function

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13
Q

How does ROS damage lipids?

A

free radical extract hydrogen atom from unsaturated FA, lipid radical formed, react with oxygen to produce a lipid peroxyl radical, chain reaction disrupts hydrophobic environment

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14
Q

Name the endogenous oxidant sources

A

electron transport chain, nitric oxide synthases and NADPH oxidases

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15
Q

Name the exogenous sources of oxidants

A

radiation, pollutants, drugs and toxins

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16
Q

How many types of nitric oxide synthases are there and which one is most important?

A

3 types, iNOS is most important: oxidative burst in phagocytes

17
Q

What is an oxidative burst?

A

The rapid released of ROS and RNS from phagocytic cells to destroy invading bacteria.

18
Q

Which enzymes are important in oxidative burst?

A

NADPH oxidase, iNOS, myeloperoxidase

19
Q

Which enzymes work together as a cellular defence against oxidative damage?

A

superoxide dismutase and catalase

20
Q

What is the function of superoxide dismutase?

A

converts superoxide to hydrogen peroxide and oxygen and stops superoxide initiating a chain reaction

21
Q

Where is SOD expressed most?

A

In mitochondria to mop of superoxides from ETC

22
Q

What is the function of catalase?

A

converts hydrogen peroxide to water and oxygen and protects against oxidative burst

23
Q

How does glutathione work?

A

thiol group of Cys residue donates electron to ROS, two GSHs react to form GSSG via the enzyme glutathione peroxidase

24
Q

How is GSSG reduced back to GSH?

A

glutathione reductase, transfers electrons from NADPH to disulfide bond to break it

25
Q

Which vitamins are free radical scavengers?

A

vitamin E and vitamin C

26
Q

How do vitamins protect against oxidative damage?

A

vitamin E is oxidised to prevent lipids being oxidised and vitamin C regenerates the reduced formed of vitamin E

27
Q

Do for vitamins require enzymes to protect against oxidative damage?

A

No

The reactions are non-enzymatic

28
Q

Name 2 other free radical scavengers

A

uric acid and melatonin

29
Q

What happens in galactosaemia that makes the patient susceptible to oxidative damage?

A

increased activity of aldose reductase, more NADPH consumed, less NADPH available to reduce glutathione (GSSG), compromised defence against ROS

30
Q

Which enzymes can be deficient in galactosaemia?

A

galactokinase, galactose-1-P uridyl transferase, UDP-galactose-epimerase

31
Q

How could G6PDH deficiency affect oxidative stress?

A

less pentose phosphate pathway, limits amount of NADPH produced, less NADPH available for reducing glutathione, more susceptible to oxidative damage

32
Q

How is paracetamol normally metabolised?

A

Safely metabolised through conjugation with sulphate or glucuronide

33
Q

What usually reduces the effects of NAPQI?

A

Glutathione

34
Q

How does N-acetylcysteine work?

A

It boosts glutathione levels so cells are less susceptible to oxidative damage and levels of NAPQI can be reduced.

35
Q

What is ischaemia reperfusion injury?

A

Reperfusion of oxygenated blood after ischaemia that results in more damage.

36
Q

Why does the reperfusion injury occur?

A

ROS are produced due to incomplete metabolism and antioxidants are lost in ischaemia

37
Q

Name some diseases that can result from oxidative stress

A

multiple sclerosis, Parkinson’s, cancer, rheumatoid arthritis, COPD, pancreatitis

Metabolism (17 decks)

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