Updated: 5/29/2019

Electron Transport Chain

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Overview 
  •  Function  
    • couple energy stored in electron acceptors (NADH, FADH2) to ATP synthesis
      • process called oxidative phosphorylation 
        • 3 ATPs per NADH
          • NADH enters mitochondria from production in cytosol via
            • malate-aspartate shuttle
            • glycerol-3-phosphate shuttle
        • 2 ATPs per FADH2
          • lower energy content than NADH
  • Pathway 
    • located in inner mitochondrial membrane
    • series of carrier enzymes
      • NADH and FADH2 create a proton gradient across the inner membrane
      • pass electrons in a stepwise fashion
      • oxygen is the final electron acceptor
      • flow of proton back down concentration gradient drives F0F1 ATP synthase complex
        • net production of ATP
  • Clinical importance
    • electron transport inhibitors  
      • disrupt membrane bound carrier enzymes
        • result
          • ↓ proton gradient
          • ↓ ATP synthesis
          • ↓ O2 consumption
          • ↑ intracellular NADH/NAD+ ratio
      • CO 
        • source
          • combustion (smoking, fires, car exhaust, grills)
          • paint strippers
        • presentation
          • pulse oximeter may read 100% sat but actually O2 sat is ↓
            • pulse oximeters will read both the CO and O2 as saturating hemoglobin
            • patients exposed to CO must use a co-oximeter (that also detects carboxyhemoglobin)
          • cherry-red lips and cheeks
          • headache/nausea
          • tachypnea
          • tachycardia
        • treatment
          • 100% O2
      • CN 
        • source
          • nitroprusside administration
            • byproduct
            • give with thiosulfate to consume produced CN
          • combustion of polyurethane
            • burning furniture, mattresses
          • Mining (gold), metal extraction
        • presentation
          • seizures, tachypnea, tachycardia, headache, flushing
        • treatment
          • sodium thiosulfate
            • forms thiocyanate, less-toxic metabolite, renally excreted
          • nitrites
            • convert hemoglobin to methemoglobin (ferrous to ferric)
            • does not allow cyanide transport to mitochondria
            • must be given shortly after exposure
      • note: victims of house fires may have both CO and CN poisoning
    • ATPase inhibitors
      • directly inhibit mitochondrial ATP synthase
        • result
          • ↑ proton gradient
            • no ATP is produced because electron transport stops
      • e.g. oligomycin
    • uncoupling agents
      • "uncouples" ATP production from the proton gradient
      • ↑ permeability of membrane
        • result
          • ↓ proton gradient
          • ↑ O2, NADH consumption
          • ATP synthesis stops, but electron transport continues
            • produces heat
        • examples
          • 2,4-DNP
          • aspirin/salicylates
            • fevers often occur after aspirin overdose
          • thermogenin in brown fat
            • UCP protein
            • generates heat for newborns
Compound Site of inhibition
CO (carbon monoxide) Cytochrome c
CN (cyanide) Cytochrome c
Antimycin Cytochrome b/c1
Doxorubicin CoQ
Rotenone (pesticide) NADH dehydrogenase

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