5.5 Translocation of Protons and the Establishment of a Proton Motive Force скачать в хорошем качестве

5.5 Translocation of Protons and the Establishment of a Proton Motive Force

Proton Gradient Formation: During electron transport in mitochondria, energy is used to pump protons (H⁺) from the matrix to the intermembrane space, creating a charge separation. This process is electrogenic, generating both a pH gradient (difference in proton concentration) and a voltage gradient (membrane potential). Proton-Motive Force (PMF): The proton-motive force (Δp) combines the energy from the chemical (ΔpH) and electrical (ΔΨ) components of the gradient. This electrochemical gradient powers ATP synthesis. In mammalian mitochondria, ~80% of Δp comes from the voltage gradient (~220 mV total), while ~20% comes from the pH difference (0.5–1 pH unit). ATP Synthesis & Uncoupling: The inner mitochondrial membrane must remain impermeable to protons to maintain Δp. Proton leakage dissipates the gradient, releasing energy as heat instead of producing ATP. Uncoupling agents like 2,4-dinitrophenol (DNP) disrupt this process by carrying protons across the membrane, uncoupling oxidation from phosphorylation. This leads to continued substrate oxidation but no ATP production, causing excess fat burning and heat release. Uncoupling Proteins (UCPs): UCP1 in brown adipose tissue enables heat production (thermogenesis), especially in infants and during cold exposure in adults. Other isoforms (UCP2–UCP5) are present in various tissues, possibly regulating proton-motive force to prevent excessive electron leakage and the formation of reactive oxygen species (ROS). Applications: Understanding PMF and uncoupling mechanisms has implications for weight loss therapies and preventing mitochondrial oxidative stress.