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The electron transport chain (ETC) functions to generate ATP from a high-proton gradient established in the intermembrane space in the mitochondria.
| ETC → lots of protons in mitochondrial intermembrane space → increased ATP-producing turbine activity (Complex V; ATP synthase). |
Here are some facts the USMLE is known to test about the ETC:
2,4-dinitrophenol, ethanol, aspirin, and thermogenin are uncoupling agents. (DEATH)
An uncoupling agent destroys the H+ gradient within the inner mitochondrial membrane necessary for ATP synthesis, so compensatory over-activation measures to restore the H+ gradient yield heat.
| Uncoupling agent → protons leak back into inner mitochondrial space (i.e., do not go through Complex V) → more protons need to be pumped into intermembrane space to achieve same ATP production → more O2 required to generate same # of ATP →
Uncoupling agents ↑ O2 consumption / ATP production ratio Uncoupling agents ↑ CO2 production / ATP production ratio |
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Cyanide (CN–) causes inhibition of electron transfer to molecular oxygen.
Treatment = amyl nitrite + sodium thiosulfate
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Methemoglobinemia = “chocolate brown” blood
Fe3+ hemoglobin cannot bind oxygen, so saturation is decreased.
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In contrast to chocolate brown blood of methemoglobinemia,
| Cherry red blood = bright red lips/face/nail beds = CO poisoning.
CO poisoning causes metabolic acidosis (↓ bicarb) because ↓ O2 delivery to tissues results in lactic acidosis. |
You also need to know (random as fuck):
| Thermogenin is a protein found in the mitochondria of brown fat (brown adipose tissue) and serves to keep neonates (and hibernating animals) warm. It is also an uncoupling agent. |
The USMLE might tell you that a neonate needed surgery for removal of a mass and that the physician needed to remove some of the surrounding fat in the process. If they ask you about a potential post-surgery complication, the answer is hypothermia because of removal of brown fat. Clinically, the scenario is unlikely and completely outrageous and ridiculous, but this is how the USMLE tests thermogenin.
Finally (low-yield, but have been known to show up once in a blue moon):
Rotenone inhibits Complex I (NADH dehydrogenase)
Antimycin A inhibits Complex III
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