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Updated: Aug 8 2023

Electron Transport Chain

  • 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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