Electron transport chain ( ETC ) and Oxidative phosphorylation - USMLE step 1 Medical Biochemistry

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Electron transport chain ( ETC ) and Oxidative phosphorylation

Electron Transport Chain

Electron transport chain: uses NADH and FADH2 electrons (from glycolysis, pyruvate dehydrogenase complex, and the citric acid cycle) to form a proton gradient, coupled to oxidative phosphorylation, that drives the production of ATP
The ETC (electron transport chain) is composed of 5 multi-enzyme complexes, numbered I-V, that accept and donate electrons while molecular oxygen, O2, is the final electron acceptor
Mobile electron carriers, such as cytochrome c and coenzyme Q, shuttle electrons between various enzyme complexes of the ETC
Primary NADH electron transport system: malate-aspartate shuttle, which transports NADH electrons to complex 1 in the mitochondria.

Less commonly used NADH electron transport system: glycerol-3-phosphate shuttle
Theoretically: 1 NADH yields 3 ATP and 1 FADH2 yields 2 ATP (because FADH2 electrons are transferred to complex II, a lower energy level than NADH)

However, since NADH from glycolysis needs to be transported into the mitochondria and the mitochondrial membrane "leaks" protons, the actual yields are smaller
As electrons flow through the ETC, protons (H+) are pumped into the mitochondrial inter-membrane space → this creates an electrochemical protein gradient
ATP Synthase (Complex V): uses the electrochemical proton gradient created by the ETC to pump protons (H+) back into the mitochondrial matrix to produce ATP from ADP and Pi
Toxins that disrupt any component of the ETC disrupt the aerobic production of ATP → tissues that depend highly on aerobic respiration, such as the CNS and the heart are particularly affected
Amobarbital (known as amytal) and rotenONE bind to NADH dehydrogenase (complex 1) → directly inhibit electron transport

Antimycin A binds to cytochrome c reductase (complex III) → directly inhibits electron transport

Carbon monoxide and Cyanide bind to Cytochrome C oxidase (complex IV) → directly inhibit electron transport
Oligomycin (a macrolide) inhibits ATP synthase (complex V) by blocking its proton channel
2,4-Dinitrophenol and ↑ doses of aspirin increase the permeability of the inner mitochondrial membrane → ↓ proton gradient and ↑ oxygen consumption → heat generated instead of ATP (explains the fever generated following toxic doses of aspirin)
Thermogenin in brown fat is an uncoupling agent that disrupts the proton gradient → used to generate heat in animals

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