Mechanism of Weight Loss with DNP: Disrupting Chemiosmosis in Mitochondria

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In the 1940s, dinitrophenol (DNP) was used by physicians for weight loss but was discontinued due to safety concerns after patient deaths. DNP functions by uncoupling the chemiosmotic process in mitochondria, making the inner mitochondrial membrane permeable to protons (H+). This disrupts the proton gradient necessary for ATP synthesis via ATP synthase, leading to a situation where respiration continues but ATP production is diminished. As a result, the cell experiences a shortage of ATP, prompting an increase in respiration to compensate, which burns more energy without generating usable ATP. While some ATP can still be produced through alternative pathways, the primary mechanism of chemiosmosis is impaired, leading to weight loss through increased energy expenditure.
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This was a question given to one of my classes on an exam some time back. I wonder if anyone here can nail it. I know the answer now of course, but I'm curious to see what the posters will think.

In the 1940s, some physicians prescribed low doses of a drug called dinitrophenol (DNP) to help patients lose weight. This unsafe method was abandoned after a few patients died. DNP uncouples the chemiosmotic machinery by making the lipid bilayer of the inner mitochondrial membrane leaky to H+. Explain how this causes weight loss.
 
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Ah, a biochem question :smile: normally a proton gradient is set up along the respiratory chain, at the end of the chain the ATP synthase unit uses this proton gradient to synthesize ATP. The uncoupler neutrolizes the proton gradient by making the membrane leaky, thus no ATP can be made. DNP doesn't prevent respiration from taking place, so energy is still being burned but it is not turned into anything usefull. There isn't enough ATP in the cell, so it will upregulate respiration, burning more energy :P
 
You're basically right, but you'd only get half-credit for that answer. The professor wanted a more specific description of what would happen. ATP can still be made, just not through chemiosmosis.
 

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