Question

(1) Dintrophenol (DNP) is a small molecule that renders membranes permeable to protons. In the 1940s, small amounts of this highly toxic compound were given to patients to induce weight loss. DNP was effective in melting away the pounds, especially promoting the loss of reserves. Can you explain how it might cause such loss? As an unpleasant side reaction, however, patients had an elevated temperature and sweated profusely during the treatment. provide an explanation for these symptoms.

Answer 1

Answer:

• By uncoupling protons across mitochondrial inner membrane 2,4-dinitrophenol (DNP) causes dissipation of the proton gradient. Loss of proton gradient results in inhibition of ATP synthesis.
• Cells continue to oxidize glucose/food molecules to feed high-energy electrons into the electrontransport chain, but H+ ions pumped across the membrane flow back into the mitochondria in a futile cycle. As a result, the energy of the electrons cannot be tapped to drive ATP synthesis, and instead is released as heat.
• 
  Matrix high pH Cytosol low pH OH он NO2 NO NO2 NO diffusion NO2 2,4-Dinitrophenol (DNP) NO2
  
• The above figure shows the uncoupling of H+ by 2,4-Dinitrophenol (DNP)
• elevated temperature in patients treated with 2,4-Dinitrophenol (DNP): DNP treated patients lose weight because their fat reserves are used more rapidly to feed the electrontransport chain, and the whole process simply "wastes" energy as heat, which explains elevated body temperature and sweating.
• Even brown fat cells utilize similar mechanism to produce heat, such cells are abundant in newborn humans and in hibernating animals. Brown fat cells are packed with mitochondria that leak part of their H+ gradient futilely back across the membrane for the sole purpose of warming up the organism.