5D: Oxygen Deficiency and Oxygen Toxicity
List the uncouplers of oxidative phosphorylation?
- 2,4 - Dinitrophenol - Pentochlorophenol - Valinomycin - Oligomycin - Atractyloside
Describe the structure of Hypoxia-inducible factors (HIFs)
- a stable B subunit - 3 labile a subunits - HIF-1a - HIF-2a - HIF-3a
What is valinomycin?
- an uncoupler of oxidative phosphorylation - transport antibiotic - dissipates the membrane potential
What is 2,4 - Dinitrophenol?
- an uncoupler of oxidative phosphorylation - weak, lipid-soluble organic acids that transport protons across the inner mitochondrial membrane - dissipating proton gradient
What is pentachlorophenol?
- an uncoupler of oxidative phosphorylation - weak, lipid-soluble organic acids that transport protons across the inner mitochondrial membrane - dissipating proton gradient
What is oligomycin?
- antibiotic - prevents ATP synthesis by blocking proton channel in the F1F0-ATP synthase
What are peroxidases?
- destroy hydrogen peroxide by reacting it with an organic substrate - most important substrate is glutathione
What is catalase?
- heme-containing enzyme that destroys hydrogen peroxide - present in blood and tissues - 40% of total protein in peroxisomes
describe the role of reactive oxygen species in immunity
- phagocytic cells use reductive oxygen species for intracellular killing - create reactive oxygen species in phagocytic vacuoles
What is atractyloside?
- plant product - blocks ATP/ADP antiporter in the inner mitochondrial membrane - resulting in a lack of ADP in the mitochondrial matrix stopping ATP synthesis and electron flow
What is antimycin A?
- poison that inhibits oxidative phosphorylation - antibiotic produced by streptomycete - block electron flow through complex III
What is carbon monoxide?
- poison that inhibits oxidative phosphorylation - bind to the ferrous form of iron on the heme of hemoglobin
What is cyanide?
- poison that inhibits oxidative phosphorylation - inhibit complex IV by binding to the ferric form of iron on the heme of cytochrome ala3
What is rotenone?
- poison that inhibits oxidative phosphorylation - inhibits electron flow from the iron-sulfur centers in complex 1 to ubiquinone - obtained from the roots of some tropical plants
What is azide?
- poison that inhibits oxidative phosphorylation - inhibit complex IV by binding to the ferric form of iron on the heme of cytochrome ala3
What is superoxide dismutase?
- protects cells by destroying reactive oxygen species - decomposes superoxide radical into hydrogen peroxide and molecular oxygen - found in the mitochondria and cytoplasm
List the enzymes that function in destruction of reactive oxygen species
- superoxide dismutase - catalase - peroxidases
What is ischemia?
a local obstruction of the blood supply
What is infarction?
an outcome of ischemia that includes cell death and tissue necrosis
Describe the effects of anaerobic glycolysis on cells
causes an accumulation of lactic acid that contributes to cell death by: - acidifying the tissue - activating lysosomal enzymes
What are some examples of infarction?
gangrene, acute myocardial infarction, thromboembolic stroke
What is glutathione reductase?
keeps glutathione in the reduced state
What is glutathione peroxidase?
uses reduced glutathione to destroy hydrogen peroxide
Describe the mechanisms of action of HIFs
-in the presence of oxygen, the a subunits are hydroxylated, triggering proteasomal degradation - in the absence of oxygen, the a subunits can move to the nucleus and combine with the B subunit to form a transcription factor that binds to hypoxia responsive elements in the promoters
List the poisons that inhibit oxidative phosporylation.
1. rotenone 2. antimycin A 3. cyanide 4. azide 5. carbon monoxide
