Biochem final pt. 4 ETC and ATP Synthase

Purpose of the Electron Transport Chain (ETC)

To transfer electrons from NADH/FADH₂ to O₂ and use the energy to pump protons, creating a proton gradient for ATP production

Location of ETC

Inner mitochondrial membrane

Final electron acceptor in ETC

Oxygen (O₂), reduced to water (H₂O)

Complex I (name enzyme first)

NADH dehydrogenase. Accepts 2 electrons from NADH, transfers to Coenzyme Q (CoQ), pumps 4 protons into intermembrane space

Complex II

(Succinate Dehydrogenase) Accepts electrons from FADH₂, transfers to CoQ, does not pump protons

Complex III

Ubiquinol Cytochrome C oxidoreductase (Cytochrome bc₁ Complex) Accepts electrons from reduced CoQ (QH₂), transfers to cytochrome c, pumps 4 protons

Complex IV

(Cytochrome c Oxidase) Accepts electrons from cytochrome c, transfers to O₂ to form H₂O, pumps 2 protons

Mobile electron carriers in ETC

Coenzyme Q (ubiquinone) and Cytochrome c

How many protons pumped per NADH

10 protons (4 from Complex I, 4 from Complex III, 2 from Complex IV)

How many protons pumped per FADH₂

6 protons (no Complex I contribution)

Purpose of proton gradient (PMF)

Stores potential energy that drives ATP synthesis by ATP synthase

Components of Proton-Motive Force (PMF)

ΔpH (proton concentration difference) and ΔΨ (electric voltage difference)

What is the Chemiosmotic Theory

Proton gradient across inner mitochondrial membrane drives ATP synthesis

Structure of ATP Synthase

F₀ subunit (membrane channel) and F₁ subunit (catalytic head in matrix)

Mechanism of ATP Synthase

Proton flow through F₀ rotates the γ subunit, driving conformational changes in F₁ to produce ATP

Proton requirement per ATP

~3 protons for ATP synthase rotation + 1 proton for phosphate transport → ~4 protons per ATP

Effect of uncouplers (e.g., DNP)

Destroy the proton gradient → ETC still works, but no ATP is made

Examples of ETC inhibitors

Rotenone (blocks Complex I), Antimycin A (blocks Complex III), Cyanide (blocks Complex IV)

Effect of oligomycin

Inhibits ATP synthase → proton flow stops → ETC slows due to backpressure

Why FADH₂ produces less ATP than NADH

Enters ETC at Complex II, bypassing Complex I and fewer protons pumped

Relationship between ETC and oxygen

Without oxygen, ETC backs up and stops because there’s no final electron acceptor

Key evidence for chemiosmotic model

Isolated mitochondria experiments showed ATP synthesis depends on a proton gradient