Cell signaling by oxygen; reactive oxygen Flashcards
Oxygen Homeostasis
- depends on partial pressure of oxygen in tissues
- mainly controlled by blood flow
- too little = ATP depletion
- too much = oxidative damage
Reactive oxygen species
- oxygen-containing molecules that oxidize substrates
- oxidation alters function
- ROS are free radicals or free radical precursors
free radicals
- molecule, atom, or ion that contains an unpaired electron
- very reactive - unpaired electrons don’t like the single life
ROS that are free radicals
- superoxide
- nitric oxide
- hydroxyl radical
- nitrite radical
Which free radical ROs are “very aggressive”?
- hydroxl radical
- nitrite radical
very fast to react and cause a great deal of damage
ROS that are free radical precursors
- hydrogen peroxide
- hypochlorite anion
What gives pus a green color?
MPO = myeloperoxidase
Sources of ROS
Ionizing radiation
- Radon disintegration
- X-ray
- Cosmic rays
Sources of ROS
Metal Catalysts
Fe2+
Sources of ROS
Metabolim
Mitochondrial ubiquinon-cycle
Sources of ROS
Enzymatic Catalysts
- NADPH oxidases (neutrophils and macrophages)
- Myeloperoxidase (neutrophils)
- Nitric oxide synthase (endothelial cells)
ischemia
an inadequate blood supply to an organ or part of the body, especially the heart muscles.
Reperfusion
the action of restoring the flow of blood to an organ or tissue, typically after a heart attack or stroke.
Oxidation and/or nitration caused by ROS can damage what?
- lipids
- proteins
- DNA
What damage happens to lipids from oxidation/ nitration?
- damage to membranes
- ionic gradients collapse
- enzymes spill
What damage happens to proteins from oxidation/ nitration?
- failing enzymes
- failing transporters
- failing cell function
- failing cell signalin
What damage happens to DNA from oxidation/nitration?
- altered expression
- failure to protect
- failure to repair
Damage from ROS to lipids, proteins, and DNA leads to cell injury. From cell injury, where can things lead to?
- apoptosis
- necrosis which leads to damage to tissue and whole organism
Defenses against ROS
- Superoxide dismutase/Catalase
- Glutathione cycle
- Control of iron (Fe2+ and Fe3+)
- Antioxidants
Examples of Antioxidants
- Ascorbic Acid
- Vit. E
- Vit. A
- beta-carotene
- uric acid
Oxygen sensing
- Central sensors in brain
- peripheral sensors: carotid bodies and aortic bodies
- Control center: Brain Stem (Medulla)
Effectors of Oxygen Sensing
Respiratory muscles that deal with depth and frequency of breath
Cell membrane heme-protein
normal and low p(O2)
normal: O2-bound heme-protein keeps K+ channels open
low: empty heme-protein closes K+ channels
ATP production in mitochondria maintains low AMP in cytosol
normal and low p(O2)
normal: low AMP keeps AMP-kinase inactive
low: high AMP via AMP-kinase cause K+ channels to close
Superoxide production by cytosolic NADPH-oxidase
normal and low p(O2)
normal: superoxide oxidizes K+ channels and keeps channels open
low: less superoxide causes K+ channels to close
Hypoxia inducible factor (HIF-1)
- expressed in many cells
- under hypoxia, will upregulate expression of genes to let cells cope with hypoxia or return from hypoxia to normoxia
