BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012
Chapter 16. ENERGY METABOLISM
16.2.Oxidative Phosphorylation of ADP
16.2.3.Uncoupling of Respiration and Phosphorylation
Certain chemical substances (protonophores) are capable of transporting protons or other ions (ionophores) from the intermembrane space across the membrane into the matrix, bypassing the proton channels of ATP synthase. As a result, the Electrochemical Potential collapses, and ATP synthesis ceases. This phenomenon is known as the uncoupling of Respiration and phosphorylation. Consequently, ATP levels decrease while ADP levels increase. In this state, the oxidation rate of NADH and FADH2 accelerates, as does oxygen consumption, but the energy is released as heat, and the P/O ratio drops sharply. Typically, uncouplers are lipophilic compounds that readily cross Cell/29.html">The Lipid Bilayer of the membrane. One such substance is 2,4-dinitrophenol, which easily transitions between ionized and non-ionized forms, picking up a proton in the intermembrane space and carrying it into the matrix.
Uncouplers can also include certain Pharmaceuticals, such as dicumarol (an anticoagulant), as well as endogenous metabolites like bilirubin (a heme Catabolism product) and thyroxine (a thyroid hormone). All of these substances exhibit uncoupling activity only at high concentrations.
Last update: 06/08/2026
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