Harpers

THE RESPIRATORY CHAIN & OXIDATIVE PHOSPHORYLATION / 97PhospholipidbilayerOligomycinF 0–ProtoncircuitMitochondrialinner (coupling)membraneH +Uncoupling agentsH +ATPSYNTHASEADP + P iINSIDEH + H +F 1ATP + H 2 OH + IIIH +–translocationProtonINADH+ H + NAD +H 2 O1 /2O 2QCIVpH gradient (∆pH)H +Respiratory(electrontransport)chainElectricalpotentialOUTSIDE+(∆Ψ)Figure 12–8. Principles of the chemiosmotic theory of oxidative phosphorylation. The main proton circuitis created by the coupling of oxidation in the respiratory chain to proton translocation from the inside to theoutside of the membrane, driven by the respiratory chain complexes I, III, and IV, each of which acts as a protonpump. Q, ubiquinone; C, cytochrome c; F 1 , F 0 , protein subunits which utilize energy from the proton gradientto promote phosphorylation. Uncoupling agents such as dinitrophenol allow leakage of H + across themembrane, thus collapsing the electrochemical proton gradient. Oligomycin specifically blocks conductionof H + through F 0 .Table 12–1. States of respiratory control.Conditions Limiting the Rate of RespirationState 1 Availability of ADP and substrateState 2 Availability of substrate onlyState 3 The capacity of the respiratory chain itself, whenall substrates and components are present insaturating amountsState 4 Availability of ADP onlyState 5 Availability of oxygen onlyThe Chemiosmotic Theory Can Accountfor Respiratory Control and the Actionof UncouplersThe electrochemical potential difference across the membrane,once established as a result of proton translocation,inhibits further transport of reducing equivalentsthrough the respiratory chain unless discharged by backtranslocationof protons across the membrane throughthe vectorial ATP synthase. This in turn depends onavailability of ADP and P i .Uncouplers (eg, dinitrophenol) are amphipathic(Chapter 14) and increase the permeability of the lipoidinner mitochondrial membrane to protons (Figure12–8), thus reducing the electrochemical potential andshort-circuiting the ATP synthase. In this way, oxidationcan proceed without phosphorylation.