Cell signaling by oxygen; reactive oxygen

Question 1

Oxygen Homeostasis

Answer 1

• depends on partial pressure of oxygen in tissues
• mainly controlled by blood flow
• too little = ATP depletion
• too much = oxidative damage

Question 2

Reactive oxygen species

Answer 2

• oxygen-containing molecules that oxidize substrates
• oxidation alters function
• ROS are free radicals or free radical precursors

Question 3

free radicals

Answer 3

• molecule, atom, or ion that contains an unpaired electron

- very reactive - unpaired electrons don’t like the single life

Question 4

ROS that are free radicals

Answer 4

• superoxide
• nitric oxide
• hydroxyl radical
• nitrite radical

Question 5

Which free radical ROs are “very aggressive”?

Answer 5

• hydroxl radical
• nitrite radical

very fast to react and cause a great deal of damage

Question 6

ROS that are free radical precursors

Answer 6

• hydrogen peroxide

- hypochlorite anion

Question 7

What gives pus a green color?

Answer 7

MPO = myeloperoxidase

Question 8

Sources of ROS

Ionizing radiation

Answer 8

• Radon disintegration
• X-ray
• Cosmic rays

Question 9

Sources of ROS

Metal Catalysts

Answer 9

Fe2+

Question 10

Sources of ROS

Metabolim

Answer 10

Mitochondrial ubiquinon-cycle

Question 11

Sources of ROS

Enzymatic Catalysts

Answer 11

• NADPH oxidases (neutrophils and macrophages)
• Myeloperoxidase (neutrophils)
• Nitric oxide synthase (endothelial cells)

Question 12

ischemia

Answer 12

an inadequate blood supply to an organ or part of the body, especially the heart muscles.

Question 13

Reperfusion

Answer 13

the action of restoring the flow of blood to an organ or tissue, typically after a heart attack or stroke.

Question 14

Oxidation and/or nitration caused by ROS can damage what?

Answer 14

• lipids
• proteins
• DNA

Question 15

What damage happens to lipids from oxidation/ nitration?

Answer 15

• damage to membranes
• ionic gradients collapse
• enzymes spill

Question 16

What damage happens to proteins from oxidation/ nitration?

Answer 16

• failing enzymes
• failing transporters
• failing cell function
• failing cell signalin

Question 17

What damage happens to DNA from oxidation/nitration?

Answer 17

• altered expression
• failure to protect
• failure to repair

Question 18

Damage from ROS to lipids, proteins, and DNA leads to cell injury. From cell injury, where can things lead to?

Answer 18

• apoptosis

- necrosis which leads to damage to tissue and whole organism

Question 19

Defenses against ROS

Answer 19

• Superoxide dismutase/Catalase
• Glutathione cycle
• Control of iron (Fe2+ and Fe3+)
• Antioxidants

Question 20

Examples of Antioxidants

Answer 20

• Ascorbic Acid
• Vit. E
• Vit. A
• beta-carotene
• uric acid

Question 21

Oxygen sensing

Answer 21

• Central sensors in brain
• peripheral sensors: carotid bodies and aortic bodies
• Control center: Brain Stem (Medulla)

Question 22

Effectors of Oxygen Sensing

Answer 22

Respiratory muscles that deal with depth and frequency of breath

Question 23

Cell membrane heme-protein

normal and low p(O2)

Answer 23

normal: O2-bound heme-protein keeps K+ channels open
low: empty heme-protein closes K+ channels

Question 24

ATP production in mitochondria maintains low AMP in cytosol

normal and low p(O2)

Answer 24

normal: low AMP keeps AMP-kinase inactive
low: high AMP via AMP-kinase cause K+ channels to close

Question 25

Superoxide production by cytosolic NADPH-oxidase

normal and low p(O2)

Answer 25

normal: superoxide oxidizes K+ channels and keeps channels open
low: less superoxide causes K+ channels to close

Question 26

Hypoxia inducible factor (HIF-1)

Answer 26

• expressed in many cells

- under hypoxia, will upregulate expression of genes to let cells cope with hypoxia or return from hypoxia to normoxia