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Physiology > Cell signaling by oxygen: Reactive Oxygen > Flashcards

Cell signaling by oxygen: Reactive Oxygen Flashcards

1
Q

Does high pO2 or low pO2 cause damage?

A

Both cause damage

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2
Q

Which free radicals cause the most damage

A

hydroxyl radical

nitrite radical

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3
Q

What are reactive oxygen species?

A

Oxygen-containing molecules that oxidize substrates

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4
Q

What are free radicals?

A

Molecule that contains an unpaired electron

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5
Q

What is the fenton reaction?

A

2 H2O2 atoms react with Iron to create water, a peroxide radical and a hydroxyl radical

2 H2O2 -Fe2+–> H2O + HOO* + *OH

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6
Q

Name 2 free radical precursors

A 
Hydrogen peroxide (H2O2)
hypochlorite anion (OCl-)
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7
Q

Describe the superoxide-nitric oxide reaction

A

H+ + O2* + NO* –> H+ + ONOO* –> *OH + *NO2

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8
Q

What reaction produces hypochlorite anion from hydrogen peroxide?

A

myeloperoxidase reaction

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9
Q

Name the 6 reactions that can generate free radicals

A 
Fenton reaction
Haber-Weiss reaction
Superoxide-nitric oxide reaction
Myeloperoxidase reaction
Hypochlorite-iron reaction
Hypochlorite-superoxide reaction
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10
Q

What is the free radical chain reaction?

A

A free radical donates its electron to a substrate (R2)

r2 becomes a free radical

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11
Q

What causes the free radical chain reaction to speed up or slow down?

A

Speeds up when highly reactive radicals are formed

Slows down when unreactive molecules are formed

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12
Q

What is usually the R1 in the free radical chain reaction? What is the resulting R2?

A

R1 is usually a macromolecule (lipid, protein)

R2 is usually an aggressive free radical (*OH or *NO2)

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13
Q

What is the result of oxidation or nitration?

A

Alters function similar to phosphorylation

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14
Q

What are the 5 sources of reactive oxygen species?

A

Ionizing radiation (X-ray, radon, cosmis rays)

Metal catalysts (Fe2+)

ROS reactions

Metabolism (ubiquinon)

Enzymatic catalysts (NADPH oxidases, macrophages)

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15
Q

What is the mitochondrial ubiquinon cycle?

A

Mitochondria generate superoxide as a by-product of electron transport by ubiquinon cycle to the electron transport chain

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16
Q

What causes the most damage during reperfusion after ischemia?

A

Reactive oxygen species burst occurs between ischemia and reperfusion

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17
Q

What produces the ROS burst after ischemia?

A

Mitochondria

18
Q

What can the ROS burst after ischemia lead to?

A

Apoptosis & necrosis

19
Q

What is an example of an ischemia?

A

Heart attack
stroke
gut torsion

20
Q

What occurs to ATP, cytosolic pH and mitochondrial potential during ischemia?

What about cytosolic Na+ and Ca2+?

A

ATP, pH, and mitochondrial potential go down

Na+ and Ca2+ increase

21
Q

Describe the production of ROS by neutrophils

A

Neutrohpil binds with NADPH oxidase (NOX)

NOX associates with RAC to produce a superoxide radical (*O2)

*O2 forms hydrogen peroxide spontaneously or by using enzyme superoxide dismutase (SOD)

Neutrophil binds myeloperoxidase vesicles

MPO makes hypochlorite from H2O2 and Cl-

  • O2 reacts with OCl- to form *OH
  • O2 and *OH kill bacteria
22
Q

What other pathway can nitric oxide take aside from cell signaling?

Why is this reaction important?

A
  • NO + *O2 –> *NO2

* NO2 is highly reactive and capable of substance nitration

23
Q

Name some of the damaging features of oxidation or nitration caused by ROS

A 
Damage to lipid membranes
Failing enzymes
Failing cell function
Altered DNA expression
Failure to repair DNA
24
Q

What are the 2 defense cycles against ROS?

A

Superoxide dismutase and catalase

GLutathione cycle

25
Q

Describe the superoxide dismutase & catalase defense cycle

A

2 *O2 –SOD–> H2O2

2 H2O2 –catalase–> O2 + H2O

26
Q

Describe the glutathione cycle

A

H2O2 + 2 GSH –> GSSG + 2 H2O

2 NADPH + GSSG –> 2 NADP+ + 2 GSH

27
Q

What is GSH?

A

Reduced glutathione

28
Q

What is GSSG?

A

Oxidized glutathione

29
Q

What are the 2 enzmes associated with the glutathione defense cycle?

A

glutathione peroxidase

glutathione reductase

30
Q

How can the control of iron defend against ROS?

A

Iron is bound to transferrin and stored in ferritin

No fenton reaction

31
Q

How can antioxidants combat ROS damage?

A

Ascrobic acid is radicalized by a free radical

2 *Asc –> dehydro-ascorbate (DH-Asc) + Asc

32
Q

Name 5 antioxidants

A 
Ascorbic acid,
Uric acid
Vitamin E
Vitamin A
Beta-carotene
33
Q

What receptors are responsible for oxygen sensing?

A

Peripheral receptors
Carotid bodies
Aortic bodies

34
Q

How do peripheral sensors control oxygen?

A

Send afferent signals to brain to increase respiration

35
Q

What cranial nerve do carotid bodies send signals to?

A

Cranial nerve 9

36
Q

Describe the depolarization of a glomus cell in the carotid body

A

Cell membrane heme closes K+ channels in response to low blood pO2

low blood pO2 initiates AMP kinase to create AMP which acts to keep K+ channels closed

NADPH oxidase produces *O2 to keep K+ channels closed

Depolarization

Depolarization opens Ca2+ voltage-gated channels

Ca2+ influx initiates release of neurotransmitters acetylcholine and dopamine

neurotransmitters activate afferent dendrites of CN IX

37
Q

What are the 3 sensors in the glomus cell that react to low pO2?

A

Cell membrane heme protein
production of AMP via AMP-kinase
Superoxide production by NADPH-oxidase

38
Q

What is HIF-1?

A

During hypoxia, Hypoxia inducible factor upregulates expression of genes that enable cells to cope or to ensure hypoxia returns to normoxia

39
Q

Describe HIF-1 during normoxia

A

prolyl-hydroxylases hydroxylate HIF-1alpha

Hydroxylated HIF-1alpha is ubiquinated

40
Q

Describe HIF-1 during hypoxia

A

In absence of O2, HIF-1alpha moves to nucleus and binds with subunit HIF-1beta and transcription factors p300/CBP

Transcription of lactate dehydrogenase, GLUT1, EPO, VEGF

Physiology (45 decks)

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