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Human Function- Exam 4 Material > Oxygen Radicals- Shiemke > Flashcards

Oxygen Radicals- Shiemke Flashcards

1
Q

why is oxygen not spontaneously reduced to water?

A

2 electrons have the same spin in O2, need to flip the spin of one of them, which is very slow

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2
Q

what catalyzes an electron spin flip in oxygen?

A

oxygenases and oxidases

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3
Q

what is conservation of spin?

A

total spin of reactants must equal the total spin of the products

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4
Q

how many electrons are required to fully reduce oxygen?

A

4

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5
Q

what happens when less the 4 electrons reduce oxygen?

A

formation of reactive oxygen species (ROS)

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6
Q

O2 + 1e = ?

A

superoxide radical

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7
Q

O2 + 2e = ?

A

hydrogen peroxide

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8
Q

O2 + 3e = ?

A

hydroxyl radical and water

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9
Q

how are ROS removed?

A

antioxidant defense systems

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10
Q

what causes diseases involving ROS?

A

too much ROS formation

too little ROS removal

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11
Q

what is the main source of ROS?

A

complex I of ETC (maybe III)

anywhere electron pairs are split, forming a radical that can react with oxygen to produce an oxygen radical

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12
Q

what shifts the ETC into a more reduced state?

A

increased NADH/NAD or decreased O2

forces reducing equivalents to be around longer, giving more time to split into radicals

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13
Q

why is hypoxia thought to be worse than anoxia?

A

hypoxia still has low levels of O2, so ETC is still working, just very slowly, so reducing equivalents are still being made
anoxia has no O2, so reducing equivalents are stuck reduced, no ROS are made

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14
Q

what role do phagocytes play in ROS production?

A

inflammation increases amount and action of phagocytes

phagocytes leak ROS and damage surroundings

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15
Q

what role do peroxisomes play in ROS production?

A

oxidize long chain fatty acids and some reducing equivalents go to O2 which forms hydrogen peroxide

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16
Q

characteristics of ROS reactions?

A
  • products and reactants are radicals
  • oxidation via radicals is faster
  • releases a lot of energy
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17
Q

what is unique about ROS?

A

no spin restriction

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18
Q

what is the most damaging ROS? why?

A 
hydroxyl radical
largest driving force for oxidation
no defenses against it
initiate radical chain reactions
immediately reacts with almost any organic compound
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19
Q

what is the radical theory of aging?

A

chronic radical production over time produces damage that can’t be fixed due to overwhelming of antioxidant systems
balance between energy towards repair and reproduction determines lifespan (humans have more repair- live longer than insects that reproduce more)

20
Q

what is the evidence supporting the radical theory of aging?

A
  • increased oxidative damage with age
  • loss of antioxidant enzymes shortens life
  • over expression of antioxidants lengthens life
  • caloric restriction increases lifespan (prevents reduction of ETC) ONLY in rats, not primates
21
Q

evidence against radical theory of aging?

A

loss of antioxidants does not affect lifespan

increase in superoxides extends lifespan

22
Q

what is an alternative theory of aging?

A

caloric restriction- keeps mTOR (regulates calorie distribution) low
low mTOR induces more autophagy to conserve available proteins- broken/old ones are broken down

23
Q

what are the 3 antioxidant enzyme systems?

A

superoxide dismutase (SOD)
glutathione peroxidase
catalase

24
Q

what does superoxide dismutase (SOD) do?

A

removes superoxide anions

2 superoxides + 2 H –>H2O2 + O2 (hydrogen peroxide is less dangerous than superoxide)

25
Q

what are the two isozymes of SOD? how do they differ?

A

Cu-Zn- located in the cytoplasm (loss leads to ALS)

Mn-SOD- located in mitochondrial matrix (loss is lethal)

26
Q

what is the radical theory of aging?

A

chronic radical production over time produces damage that can’t be fixed due to overwhelming of antioxidant systems
balance between energy towards repair and reproduction determines lifespan (humans have more repair- live longer than insects that reproduce more)

27
Q

what is the evidence supporting the radical theory of aging?

A
  • increased oxidative damage with age
  • loss of antioxidant enzymes shortens life
  • over expression of antioxidants lengthens life
  • caloric restriction increases lifespan (prevents reduction of ETC) ONLY in rats, not primates
28
Q

evidence against radical theory of aging?

A

loss of antioxidants does not affect lifespan

increase in superoxides extends lifespan

29
Q

what is an alternative theory of aging?

A

caloric restriction- keeps mTOR (regulates calorie distribution) low
low mTOR induces more autophagy to conserve available proteins- broken/old ones are broken down

30
Q

what are the 3 antioxidant enzyme systems?

A

superoxide dismutase (SOD)
glutathione peroxidase
catalase

31
Q

what does superoxide dismutase do?

A

removes superoxide anions
2 superoxides + 2 H+ –> hydrogen peroxide + O2
(hydrogen peroxide is less dangerous than superoxide)

32
Q

what are the two forms of SOD? how do they differ?

A

Cu-Zn- cytoplasm and EC (loss leads to ALS)

Mn- mitochondrial matrix (loss is lethal)

33
Q

what does catalase do? where is it located?

A

removes hydrogen peroxide
H2O2 + H2O2 –> 2 H2O + O2
located in peroxisomes, mitochondria, and cytosol

34
Q

what does glutathione peroxidase do?

A

uses glutathione (GSH) to reduce H2O2 and organic peroxides (GSH is reduced)

35
Q

what does glutathione reductase do?

A

reduces GSSG to GSH using NADPH

36
Q

what does the ratio of GSH/GSSG measure? what does it mean?

A

oxidative stress
high (lots of GSH)- good, healthy
low (lots of GSSG)- oxidative stress is present

37
Q

what part of GSH is active?

A

thiol on cysteine

38
Q

where does NADPH come from for glutathine reductase reaction?

A

pentose shunt

39
Q

what kind of diseases are linked to oxidative damage?

A

neurodegenerative diseases
Parkinson’s
Alzheimers
ALS

40
Q

what are small antioxidant molecules? what do they do?

A

small molecules that act as reductants to remove ROS

vitamins E, A, C

41
Q

alpha tocopherol is what vitamin?

A

vitamine E

42
Q

asorbate is what vitamin?

A

vitamin C

43
Q

beta carotene is what vitamin?

A

vitamin A

44
Q

how are lipid radicals removed?

A

vitamin E reduces lipid radical
vitamin C reduces vitamin E radical
glutathione peroxidase reduces vitamin C radical
glutathione reductase reduces GSSG using NADPH

45
Q

why is vitamin E a good antioxidant?

A

membrane bound, lipid soluble
reaction between it and lipid radical stops a radical chain reaction
easily recycled

Human Function- Exam 4 Material (25 decks)

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