Reactive oxidative species Flashcards

0
Q

Only 0.1-2% of electrons drop out of the ETC, so why is this a major issue?

A

-It has a high cummulative effect, 0.1-2% of each mitochondria results in alot of O2* produced

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1
Q

Why are superoxide radicals produced in miotchondria?

A
  • Electrons drop out of the ETC resulting in a free electron

- Superoxide radicals generated if the free electron is picked up by O2

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2
Q

What are the cellular defences against superoxide radicals?

A
  • Superoxide dismutase oxidises O2* to H2O2

- Catalase oxidises H2O2 to H2O+O2

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3
Q

What are hydroxyl radicals produced from and what causes there production?

A
  • H2O2 or O2

- Ionising radiation, eg, UV, X-rays, g-rays

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4
Q

What are hydroxyl radicals particularly damaging to?

A

-Cell membranes and DNA

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5
Q

How is NO* produced in the body?

A

-From arginine

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6
Q

Why is NO* produced in the body if it is harmful?

A

-Important signalling molecule

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7
Q

How is peroxynitrite produced?

A

-NO+O2->ONOO

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8
Q

What is peroxynitrite associated with?

A

-Inflammation

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9
Q

What is cells primary defence against ROS?

A

-Glutathione

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10
Q

How does glutathione act as an antioxidant?

A

-Donates H+ from cysteine to reduce ROS

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11
Q

What catalyses the reduction of ROS by glutathione?

A

-Glutathione peroxidase

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12
Q

What is the oxidised form of glutathione?

A

-GSSG

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13
Q

What are examples of exogenous oxidising agents?

A
  • Drugs-> primaquine-> anti-malarial

- Toxins->paraquate-> poisons cells, often fatal

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14
Q

What is the secondary cellular defence against ROS?

A

NADPH

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15
Q

Where is NADPH produced?

A

-By G6PD in the pentose phosphate pathway

16
Q

How is NADPH the secondary defence to ROS?

A

-Reduces GSSG back to GSH, catalysed by GSH reductase, therefore freeing up the antioxidant

17
Q

How is NADPH important in maintaining protein structure?

A

-DSB formation is in equilibrium, constantly being made and constantly reduced by NADPH in order to maintain proper protein structure and stop denaturation

18
Q

Why is NADPH important in galactosaemia?

A
  • Galactose accumulates in the eye and is oxidised to galactitol by aldose reductase
  • This reaction uses NADPH, producing NADP+
  • There is no NADPH to keep DSB from forming leading to cataracts
19
Q

Why is NADPH significant in G6PD deficiency?

A
  • No G6PD to reduce NADP+ to NADPH
  • No NADPH to reduce GSSG
  • Inappropriate DSB formation and ROS damage
  • Can lead to the formation of heinz bodies and haemolysis
20
Q

Name some exogenous antioxidants

A
  • Vitamins C, E, A
  • Flavenols - b-carotene
  • Minerals- selenium and zinc
21
Q

What are the steps of protection against H2O2?

A
  • Glutathione reduces H2O2 to H2O and O2
  • NADPH replenishes GSH
  • NADPH replenished by PPP
22
Q

When does oxidative stress occur?

A
  • When there is an imbalance between ROS and protective mechanisms
    i. e increased production or saturated defences
23
Q

What is lipid peroxidation?

A

-Reaction of ROS with unsaturated lipids to form lipid peroxides

24
Q

Which lipids result in the most damage after undergoing peroxidation?

A

-Those in cell membranes

25
Q

What clinical condition are lipid peroxidases associated with?

A

-CVD

26
Q

What is ischaemic reperfusion injury?

A
  • Heart becomes anoxic due to blockage
  • Breakdown of clot leads to sudden influx of blood with high O2
  • Lots of superoxide radicals produce injury
27
Q

List a few diseases associated with oxidative stress?

A
  • Cancer
  • Emphysema
  • Pancreatitis
28
Q

What is oxidative burst?

A

-Rapid release of H2O2 and O2* from cells, particularly neutrophils and macrophages, used to damage bacteria which have been engulfed or bacteria which surrounds the cell

29
Q

What enzyme allows O2* to be produced?

A

-NADPH oxidase