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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Questions (3)
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(M1.BC.14.1) After being warned by the locals not to consume the freshwater, a group of American backpackers set off on a week-long hike into a region of the Ecuadorean Amazon forest known for large gold mines. The group of hikers stopped near a small stream and used the water they filtered from the stream to make dinner. Within the next half hour, the hikers began to experience headaches, vertigo, visual disturbances, confusion, tachycardia, and altered levels of consciousness. Which of the following enzymes was most likely inhibited in this group of hikers? Tested Concept

QID: 106294
1

NADH dehydrogenase

19%

(6/31)

2

Succinate dehydrogenase

10%

(3/31)

3

Cytochrome bc1 complex

3%

(1/31)

4

Cytochrome c oxidase

58%

(18/31)

5

ATP synthase

10%

(3/31)

M 1 E

Select Answer to see Preferred Response

(M1.BC.14.18) An 18-year-old college student presents to the ED straight from chemistry lab where he ingested an unknown compound. He complains of a headache, and is flushed, tachypneic and tachycardic. Suspecting cyanide poisoning, you administer amyl nitrite which causes which of the following? Tested Concept

QID: 100083
1

Oxidation of ferrous iron in hemoglobin to ferric iron

48%

(20/42)

2

A decrease in serum methemoglobin levels

7%

(3/42)

3

Formation of thiocyanate

17%

(7/42)

4

Chelation of the residue

12%

(5/42)

5

Increase in intracellular NADH/NAD+ ratio

10%

(4/42)

M 1 E

Select Answer to see Preferred Response

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