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MCM Test 1 > B2.010 Oxidative Balance in Ischemic Damage and Blood Pressure > Flashcards

B2.010 Oxidative Balance in Ischemic Damage and Blood Pressure Flashcards

1
Q

what are the 4 primary ROS?

A

molecular O2
OH- anion
OH* radical
superoxide O2-*

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2
Q

what nitrogen species is reactive?

A

nitric oxide NO*

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3
Q

what species have unstable O-O bonds?

A

H2O2 hydrogen peroxide

ONOO- peroxynitrite

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4
Q

what is the pathways for the interconversion of ROS?

A

O2 + e- makes superoxide O2-*
2O2-* + 2H+ is catalyzed by SOD to make H2O2 and O2
H2O2 interacts with free metal in the Fenton rxn to produce HO* radical and OH- anion

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5
Q

how is NO* converted to HO* and NO2?

A

NO* + O2-* make ONOO-

ONOO- and H+ make HO* and NO2

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6
Q

what are 4 processes enabled by ROS?

A

energy production, signaling molecules, inflammation/immunity, cell redox balance

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7
Q

what proteins are related to ROS processes?

A

mitochondrial EC chain, nitric oxide synthase, AA metabolism, NADPH oxidase, cyt P450, xanthine oxidase

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8
Q

in oxidative stress, what do ROS chemically attack?

A

nucleic acid structures, amino acid side chains, double bonds of unsaturated fatty acids

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9
Q

what anti-oxidant enzymes are located within the mitochondria?

A

SOD2
Glutathione Peroxidase/Reductase
Peroxiredoxin (3 or 5)/ Thioredoxin Reductase 2

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10
Q

what anti-oxidant enzymes are located in the cytoplasm?

A

catalase
SOD1
Glutathione Peroxidase/Reductase
Peroxiredoxin/ Thioredoxin Reductase 1

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11
Q

what antioxidant makes up 1% of soluble protein?

A

superoxide dismutase (SOD)

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12
Q

what enzyme turns peroxide into water and oxygen?

A

catalase

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13
Q

what is the most important non-enzymatic antioxidant? (as noted by Dr. Swint-Kruse)

A

glutathione

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14
Q

what are hydrophilic non-enzymatic antioxidants?

A

glutathione, cysteine, vitamin C, urate, bilirubin, metal binding proteins

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15
Q

what are hydrophobic non-enzymatic antioxidants?

A

vitamin E, beta carotene

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16
Q

how do non-enzymatic antioxidants work?

A

accept or donate electrons becoming radicals themselves, new radicals are more stable than the neutralized radical due to resonance

17
Q

what is the function of the e- transport chain?

A

create a proton gradient for ATP production by passing e- down chain

18
Q

what percentage of e- leak from the chain and don’t make it through complex 4?q

A

1-4%

19
Q

what is the fate of e- that don’t make it through the chain?

A

form superoxide with molecular oxygen

20
Q

what chemicals completely block the e- transport chain and how?

A

CN and CO, by blocking complex 4 function

21
Q

if a large number of substrates feed the citric acid cycle, what are the ROS and ATP outcomes?

A

ROS and ATP both increase

22
Q

how could a transcription factor counter-act mitochrondrial stress caused by an influx in substrates feeding the citric acid cycle?

A

make more ADP to slow down citric acid cycle

23
Q

what happens to the ROS balance in ischemia and reperfusion?

A

wild swings

24
Q

what are the results of ischemia on mitochondrial function?

A

ATP synthase is blocked due to lack of oxygen, which blocks proton gradient and causes leakage of free e-

25
Q

how long does it take for cellular ATP to deplete under ischemic conditions?

A

4 min

26
Q

what accumulates after ATP depletion?

A

AMP, a precursor for ADP

27
Q

what is AMP metabolized to in ischemic conditions?

A

adenosine and hypoxanthine

28
Q

what is AMP metabolized to in reperfused conditions?

A

uric acid

29
Q

what is the result of ATP depletion on ion gradients?

A

ion gradients collapse due to impaired transporter function

30
Q

what does Ca ion gradient disruption lead to?

A
  1. activation of nitric oxide synthase
  2. proteolytic cleavage of xanthine dehydrogenase
  3. activation of the proteolytic enzyme calpain
  4. release of excitatory neurotransmitters such as glutamate
  5. activation of membrane phospholipase A2**
31
Q

what is the purpose of activation of NOS in reperfusion?

A

helps lower blood pressure via vasodilation

32
Q

what does NOS catalyze the production of?

A

NO

33
Q

what smooth muscle cell receptor binds to NO?

A

guanylyl cyclase

MCM Test 1 (23 decks)

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