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Physiology Exam 4 > Cell Signaling by Oxygen: Reactive Oxygen > Flashcards

Cell Signaling by Oxygen: Reactive Oxygen Flashcards

1
Q

O2 saturation of hemoglobin is mainly controlled by?

A

Ventilation

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2
Q

p(O2) is?

A

O2 partial pressure

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3
Q

p(O2) in tissues is mainly controlled by?

A

Blood flow

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4
Q

p(O2) damage can be caused by?

A

Too high or low p(O2)

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5
Q

Oxygen containing molecules can be?

A

Very reactive

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6
Q

ROS stands for?

A

Reactive oxygen species

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7
Q

ROS are?

A

Free radicals or their precursors

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8
Q

What is ROS?

A

Oxygen-containing molecules that oxidize substrates (lipids, proteins, DNA, etc.) to alter their function

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9
Q

What are free radicals?

A

Molecule, atom or ion containing an unpaired electron → want to find a partner (very reactive)

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10
Q

4 free radicals

A
  1. Superoxide
  2. Nitric oxide
  3. Hydroxyl radical
  4. Nitrite radical
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11
Q

2 very aggressive free radicals (cause most damage)

A
  1. Hydroxyl radical

2. Nitrite radical

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12
Q

2 free radical precursors

A
  1. Hydrogen peroxide

2. Hypochlorite ion

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13
Q

Fenton reaction

very important to know

A

2 hydrogen peroxide in presence of iron →

water + peroxide radical + hydroxyl radical

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14
Q

Haber-weiss reaction

A

Hydrogen peroxide + superoxide radical →

O2 + OH- + hydroxyl radical

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15
Q

Hydroxyl radical

A

●OH

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16
Q

Superoxide-NO reaction

A

H+ + superoxide radical + nitric oxide →

hydroxyl radical + nitrite radical

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17
Q

Hydrogen peroxide

A

H2O2

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18
Q

Hypochlorite anion

A

OCl-

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19
Q

Superoxide

A

O2●-

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20
Q

Nitrite radical

A

●NO2

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21
Q

MPO stands for?

A

Myeloperoxidase

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22
Q

MPO reaction

A

Hydrogen peroxide + chloride anion →MPO→

hypochlorite anion + water

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23
Q

Hypochlorite-iron reaction

A

H+ + OCl- + Fe2+ →

Fe3+ + Cl- + hydroxyl radical

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24
Q

Hypochlorite-superoxide reaction

A

H+ + OCl- + superoxide radical →

O2 + Cl- + hydroxyl radical

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25
Q

Free radical chain reaction

A

R1● donates unpaired electron to substrate R2 → forms free radical R2●

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26
Q

Free radical chain reaction speeds up when?

A

Highly reactive radicals formed

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27
Q

Free radical chain reaction slows down when?

A

Unreactive radicals are formed

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28
Q

Free radical terminal reaction

A

R1● (macromolecule radical) + R2● (aggressive radical) →oxidation or nitration→ R1-R2

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29
Q

5 sources of ROS

A
  1. Ionizing radiation
  2. Metal catalysts
  3. ROS reactions
  4. Metabolism
  5. Enzymatic catalysts
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30
Q

3 ways ionizing radiation causes ROS

A
  1. Radon disintegration
  2. X-ray
  3. Cosmic rays
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31
Q

Example of metal catalyst which can cause ROS

A

Fe2+

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32
Q

Enzymatic catalysts which can form ROS

A
  1. NADPH oxidases
  2. Myeloperoxidase (MPO)
  3. Nitric oxide synthase
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33
Q

NADPH oxidases found in?

A
  1. Neutrophils

2. Macrophages

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34
Q

Myeloperoxidases found in?

A

Neutrophils

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35
Q

NO synthase found in?

A

Endothelial cells

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36
Q

Mitochondria generates superoxide as byproduct of?

A

Electron transport by ubiquinon-cycle (UQ)

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37
Q

What injury is mediated by free radicals?

A

Ischemia / reperfusion

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38
Q

What does mitochondria generate after ischemia?

A

ROS burst

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39
Q

NOX stands for?

A

NADPH-oxidase

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40
Q

Initial activation of neutrophil leads to?

A

Fusion of vesicles containing NOX

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41
Q

NOX associates with?

A

Required accessory proteins including RAC

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42
Q

What is RAC?

A

Small G-protein

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43
Q

Completely assembled NOX-RAC complex uses ____ to generate ___ from?

A

Uses NADPH to generate superoxide radical from O2

44
Q

Superoxide radical dimutates to?

A

Hydrogen peroxide (spontaneous or facilitated by SOD)

45
Q

SOD stands for?

A

Superoxide dismutase

46
Q

Further activation of neutrophil leads to?

A

Fusion of vesicles containing MPO

47
Q

MPO makes?

A

Hydrogen peroxide + chloride anion → hypochlorite

48
Q

Hypochlorite

A

OCl- (bleach)

49
Q

Superoxide radical + hypochlorite forms?

A

Hydroxyl radical

50
Q

Hydroxyl radical and superoxide radical do what?

A

Kill bacteria

51
Q

SOD catalyzes?

A

Superoxide radical → hydrogen peroxidation

52
Q

How do ROS damage lipids?

A

Damage membranes → ionic gradients collapse and enzymes spill

53
Q

How do ROS damage proteins?

A
  1. Failing enzymes
  2. Failing transporters
  3. Failing cell function
  4. Failing cell signaling
54
Q

How do ROS damage DNA?

A
  1. Altered expression
  2. Failure to protect
  3. Failure to repair
55
Q

CAT stands for?

A

Catalase

56
Q

GSH is?

A

Reduced glutathione

57
Q

GSSG is?

A

Oxidized glutathione

58
Q

CAT catalyzes?

A

2 hydrogen peroxide → O2 + H2O

59
Q

SOD / CAT defense

A

SOD converted superoxide radical to hydrogen peroxide → CAT converts hydrogen peroxide to oxygen and water

60
Q

Glutathione cycle

A

Hydrogen peroxide + 2 GSH → GSSG + 2 H2O

GSSG regenerated

61
Q

How is GSSG regenerated?

A

GSSG + 2 NADPH → 2 GSH + 2 NADP+

62
Q

What catalyzes hydrogen peroxide + 2 GSH → GSSG

A

Glutathione peroxidase

63
Q

What catalyzes GSSG → 2 GSH

A

Glutathione reductase

64
Q

Iron is bound to?

A

Transferrin

65
Q

2 transferrins store?

A

2 iron atoms

66
Q

Iron uptake into cell is guarded by?

A

Transferrin receptor

67
Q

Iron is stored how?

A

Ferritin

68
Q

Asc stands for?

A

Ascorbic acid

69
Q

Asc cycle against free radicals

A

R● + Asc → Asc● + R

Asc● + Asc● → Asc + DH-Asc

70
Q

DH-ASc stands for?

A

Non-toxic dehydro-ascorbate

71
Q

1st step of Asc cycle

A

Asc reacts with R● and becomes free radical Asc●

72
Q

2nd step of Asc cycle

A

2 Asc● combine → break down unevenly into Asc and DH-Asc

73
Q

4 defenses against ROS

A
  1. SOD/CAT (Superoxide dismutase / Catalase)
  2. Glutathione cycle
  3. Iron control
  4. Antioxidants (ex: Asc)
74
Q

2 types of oxygen sensing

A
  1. Central sensors

2. Peripheral sensors

75
Q

Central sensors are located in?

A

Brain

76
Q

Peripheral sensors are located in?

A
  1. Carotid bodies

2. Aortic bodies

77
Q

Control center of oxygen sensing

A

Brain stem (medulla)

78
Q

Effectors

A

Respiratory mm. control depth and frequency of breathing

79
Q

Peripheral sensory cells are called?

A

Glomus cells

80
Q

Glomus cells are innervated by?

A

CN IX afferent dendrites

81
Q

3 sensors for p(O2)

A
  1. Cell membrane heme-protein
  2. ATP production in mitochondria maintains low AMP in cytosol
  3. Superoxide radical production by cytosolic NOX
82
Q

Heme-protein at normal p(O2)

A

Bound to O2, keeps K+ channels open

83
Q

Heme-protein at low p(O2)

A

Empty, closes K+ channels

84
Q

ATP production in mitochondria at normal p(O2)

A

Low AMP keeps AMP-kinase inactive

85
Q

ATP production in mitochondria at low p(O2)

A

High AMP via AMP-kinase cause K+ channels to close

86
Q

Superoxide radical production by cytosolic NOX at normal p(O2)

A

Superoxide radical oxidizes K+ channels (keeps channels open)

87
Q

Superoxide radical production by cytosolic NOX at low p(O2)

A

Less superoxide radical causes K+ channels closed

88
Q

Inhibition of K+ channels causes?

A

Depolarization of membrane potential

89
Q

Depolarization of membrane potential causes?

A

Opens voltage-gated Ca2+ channel

90
Q

Open voltage-gated Ca+ channel allows?

A

Influx of Ca2+

91
Q

Elevation of Ca2+ initiates?

A

Release of neurotransmitters Ach and dopamine

92
Q

Released neurotransmitters do what?

A

Activate afferent dendrites of CN IX

93
Q

Activated CN IX activates?

A

Respiratory center in medulla of brainstem

94
Q

HIF-1 stands for?

A

Hypoxia inducible factor

95
Q

HIF-1 senses?

A

O2

96
Q

Under hypoxia, HIF-1 does what?

A

Upregulates expression of genes that help cells return to normoxia

97
Q

Examples of genes HIF-1 upregulates under hypxoia

A
  1. Lactate DHN
  2. GLUT1
  3. EPO
  4. VEGF
98
Q

Lactate DHN is involved in what process?

A

Glycolysis

99
Q

GLUT1 is involved in what process?

A

Glucose uptake

100
Q

EPO is involved in what process?

A

Erythropoiesis

101
Q

VEGF is involved in what process?

A

Angiogenesis (making new vessels)

102
Q

In presence of O2, what happens to HIF-1alpha?

A

HIF-1alpha hydroxylated by prolyl-hydroxylases

103
Q

What happens to hydroxylated HIF-1alpa?

A

Ubiquinated → marked for destruction in proteosomes

104
Q

Under hypoxia, HIF-1alpha survives and does what?

A

Moves to nucleus → interacts with accessory subunit HIF-1beta and transcription factors → initiates gene transcription

105
Q

Transcription factors involved with HIF-1

A
  1. p300

2. CBP

Physiology Exam 4 (10 decks)

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