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Metabolism > Oxidative Stress > Flashcards

Oxidative Stress Flashcards

1
Q

What is superoxide?

A

O2.-

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2
Q

How is NO useful?

A

Can damage pathogens

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3
Q

List 3 cellular defences

A

Superoxide Dismutase & Catalase
Glutathione
Free radical scavengers

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4
Q

Name some free radical scavengers and how they help defend cells?

A

Vitamin E, C

They donate a H+ and e- to the free radical without the need of enzymes

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5
Q

How is vitamin C used to protect cells from damage?

A

Regenerates vitamin E which donates a H+ and e- to a free radical

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6
Q

How do Superoxide Dismutase (SOD) & Catalase protect from oxidative damage?

A

SOD catalyses conversion of O2.- –> H2O2

Catalase converts H2O2–>2H2O + O2

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7
Q

How does Glutathione protect cells from oxidative damage?

A

Reduced glutathione donates an e- from its think (SH) group to an ROS
Eg H2O2–>H2O

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8
Q

Which enzyme converts/recycles oxidised glutathione to reduced?

A

Glutathione reductase

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9
Q

Which enzyme converts reduced glutathione to oxidised?

A

Glutathione Peroxidase

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10
Q

List some ROS and RNS

A

ROS- superoxide (O2-), H2O2, OH

RNS- NO., ONOO-

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11
Q

What trace element does glutathione Peroxidase need?

A

Selenium

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12
Q

What is peroxinitrite? ONOO-

A

Not technically a free radical but IS a powerful oxidant

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13
Q

How can ROS damage DNA?

A

React with base to cause mispairing
React with sugar to break strand
Failure in repair causes mutations

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14
Q

How can ROS’ damage proteins?

A

Modify the AA causing structure to change, gain or loss of function
Cause fragmentation
All of these lead to degradation of protein

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15
Q

How can ROS’ damage lipids?

A

OH extracts H from unsaturated FA

Forms lipid radical which leads to lipid peroxidation

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16
Q

How do oxidised fatty acids lead to atheromas?

A

Oxidised LDLs engulfed by macrophage
Macrophages accumulate in intima of blood vessel wall forming foam cells then fatty streak
Atherosclerotic plaque encroaches on lumen

17
Q

What is a measure of oxidative damage in cells?

A

8-oxo-dG

Modified nucleotide

18
Q

How are ROS formed?

A

During oxidative phosphorylation

Some e- don’t reach end ETC and so reduce O2 early

19
Q

Why is superoxide so dangerous?

A

Can activate other free radicals

20
Q

What order are ROS’ made?

A

O2–> O2.- –> H2O2–> .OH–> H2O

21
Q

What is the toxic metabolite that builds up in paracetamol metabolism?

A

NAPQI

N-acetyl-p-benzo-quinone imine

22
Q

What class of drug is paracetamol?

A

Anti-pyretic

23
Q

At safe levels, what is paracetamol metabolised to?

A

It is conjugated with glucoronide OR sulphate

24
Q

What is a toxic dose of paracetamol?

A

~10g

25
Q

Why is NAPQI so toxic to hepatocytes?

A

Metabolism of NAPQI uses up stores of Glutathione
Then hepatocytes are more susceptible to oxidative damage

Causes hepatocyte proteins to covalently bind

26
Q

What antidote is used for paracetamol overdose?

A

Acetylcysteine

27
Q

How does the antidote for paracetamol overdose work?

A

Replenishes glutathione source to allow liver to continue to metabolise paracetamol

28
Q

How does NAPQI directly cause damage?

A

NAPQI causes hepatic proteins to bind covalently with each other

29
Q

How does NAPQI indirectly cause damage to hepatocytes?

A

Conjugates with glutathione
Uses up glutathione stores, leaves hepatocytes more susceptible to oxidative damage- eg lipid peroxidation, damage to DNA & proteins

30
Q

What oxidative damage does NAPQI cause?

A

Lipid peroxidation, damage to DNA & proteins

31
Q

What is NAPQI?

A

Strong oxidising agent, toxic metabolite of paracetamol metabolism

32
Q

How quickly should what antidote for paracetamol metabolism be administered?

A

Best- within 2 hours
Still effective within 8 hours
After death is inevitable due to liver failure

33
Q

Which is more important for oxidative damage- NADH or NADPH?

A

NADPH, it donates its H+/e- to oxidised glutathione to allow it to be recycled back to reduced Glutathione (GSH)

Metabolism (10 decks)

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