When the drug dinitrophenol (DNP) is added to mitochondria, the inner mitochondrial membrane becomes permeable (leaky) to protons (H+). List the effect of a leaky inner mitochondrial membrane on the following: 1. The H+ gradient across the inner membrane. 2. ETC – continues or STOPS? 3. ATP synthesis – continues or STOPS? 4. Energy – from the passive diffusion of H+ due to the "leaky" membrane– what happens to it? 5. Oxygen consumption – continues or STOPS (i.e., will oxygen continue to accept e- from complex IV and becoming reduced to H2O) ? 6. Why does DNP intake result in weight loss? Propose an explanation.
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Dinitrophenol (DNP) is a specific class of drug called an uncoupler. As an uncoupler, DNP dissipates the proton gradient established as part of the electron transport chain but does not alter the flow of electrons through the electron transport chain complexes. Effectively, this uncouples the flow of electrons from the production of ATP in the mitochondria. This means that even though electrons can move through the complexes, no proton gradient exists between the matrix and the intermembrane space to allow for ATP production. Given this information: How many net ATP would be produced from the complete oxidation of one molecule of glucose in the presence of DNP (in a liver cell) ?
Madhur L.
Normally, the flow of electrons to O2 is tightly linked to the production of ATP via the electrochemical gradient. If ATP synthase is inhibited, for example, electrons do not flow down the electron transport chain and respiration ceases. Since the 1940s, several substances—such as 2,4-dinitrophenol (DNP)—have been known to uncouple electron flow from ATP synthesis (see figure to the right). DNP dissipates the proton gradient by carrying H+ across the inner mitochondrial membrane through simple diffusion-mediated transport. DNP was once prescribed as a diet drug to aid in weight loss. A) (3pt) How would an uncoupler of oxidative phosphorylation promote weight loss? (5 sentence max) B) (2pt) Why do you suppose dinitrophenol is no longer prescribed? (5 sentence max)
Sri K.
SCIENTIFIC INQUIRY In the 1930 s, some physicians prescribed low doses of a compound called dinitrophenol $($ DNP ) to help patients lose weight. This unsafe method was abandoned after some patients died. DNP uncouples the chemiosmotic machinery by making the lipid bilayer of the inner mitochondrial membrane leaky to $\mathrm{H}^{+} .$ Explain how this could cause weight loss and death.
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