Electron Transport Chain (ETC) and Oxidative Phosphorylation

NADH starting point

NADH donates electrons to Coenzyme Q via Complex I (NADH:CoQ oxidoreductase)

FADH2 starting point

FADH2 (from succinate) donates electrons to Coenzyme Q via Complex II (Succinate Dehydrogenase)

Coenzyme Q to Cytochrome c

Electrons transfer from QH2 to cytochrome c via Complex III (CoQ:cytochrome c oxidoreductase)

Cytochrome c to O2

Electrons transfer to O2 via Complex IV (Cytochrome c oxidase)

Key principle of electron flow

Electrons flow “downhill” from low to high reduction potential

Complex I

NADH dehydrogenase / NADH:CoQ oxidoreductase

Complex II

Succinate dehydrogenase / succinate:CoQ oxidoreductase

Complex III

Cytochrome bc1 / CoQ:cytochrome c oxidoreductase

Complex IV

Cytochrome c oxidase

Coenzyme Q (Q)

Mobile hydrophobic electron carrier

Cytochrome c

Mobile hydrophilic electron carrier

Reduction potential definition

Likelihood that a carrier gains electrons

Electron acceptor

Carrier with higher (more +) reduction potential

Electron donor

Carrier with lower (more –) reduction potential

Direction of electron flow

Always “downhill” from low to high reduction potential

Proton pumping purpose

ETC uses energy from exergonic electron transfer to pump H+ into IMS

Electrochemical gradient

Created by H+ pumping

Proton-motive force

Combined electrochemical gradient

H+ per NADH

10 H+ pumped per 2 electrons from NADH

ATP Synthase F0

Proton channel in membrane

ATP Synthase F1

Catalytic subunit in matrix

γ subunit of ATP synthase

Rotor connecting F0 and F1

Binding change mechanism

Three β subunit conformations: L (loose

Regulation of respiration

Determined by ATP demand

High ATP/ADP ratio

ETC slows

Low oxygen

ETC stops because O2 is terminal electron acceptor

Cyanide

Inhibits Complex IV

Oligomycin

Inhibits F0 of ATP synthase

Metformin

Inhibits Complex I

Uncouplers

Allow electron transport and H+ pumping but block ATP synthesis

Thermogenin (UCP-1)

Uncoupler in brown fat

Glycerol phosphate shuttle

Electrons from cytosolic NADH enter ETC via FAD (Complex II entry)

Malate-aspartate shuttle

Electrons from cytosolic NADH enter ETC via Complex I

ATP yield NADH

2.5 ATP per NADH entering at Complex I

ATP yield FADH2

1.5 ATP per FADH2 entering at Complex II

ATP from cytosolic NADH

Depends on shuttle: Malate-aspartate ~2.5 ATP

Proton to ATP ratio

~10 H+ pumped per NADH