Question

2,4-dinitrophenol (DNP) and carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP) are well known uncouplers that can dissipate the proton gradient across the inner mitochondrial membrane created by the electron-transport system. Explain how this uncoupling works, in terms of the chemical properties of DNP and FCCP.

Answer 1

Uncouple agents will never disrupt the electron transport (they will not damage or disrupt the mitochondrial structure), they only inhibit the ATP synthesis and best example for this Uncouple agents are 2,4-dinitrophenol (DNP) and carbonylcyanide-ptrifluoromethoxyphenylhydrazone (FCCP) and these agents are known to bear H+ and are capable of diffusing into the matrix. Like this these two chemicals successfully reduce the electrochemical potential across the inner mitochondrial membrane and as a result you can see an inhibition of ATP synthesis.

2,4-Dinitrophenol, dicumarol and carbonyl cyanidep-trifluorocarbonyl-cyanide methoxyphenyl hydrazone (FCCP) chemicals have hydrophobic character, thus these are easily soluble in the bilipid membrane (this gives them any easy entry into the matrix in its protonated form and thus they releases a proton and can successfully dissipate the proton gradients. Another things through resonance stabilization will delocalize the charge which is there on anionic forms and thus this chemical again will diffuse back across the membrane will try to pick up a proton and will try to repeat the process) and in these chemical decouples by having the dissociable protons will carry protons from the intermembrane space to the matrix, so that the pH gradient existing there can be collapsed and all the potential energy of the proton gradient will be seen losing as mere heat. Research has showed when 2,4-dintrophenol is added to the reaction mixture, it has uncoupled electron transfer from that of ATP synthesis and as a result the oxygen is completely seen to be consumed in the absence of ADP.