Explain the mechanisms that would yield these results. Use the simulation to justify why using mitochondrial uncouplers, like DNP, would work as a diet pill.

Question

DNP (2,4-dinitrophenol) is a banned diet pill. This substance belongs to a group of molecules called mitochondrial uncouplers. Aspirin is another mitochondrial uncoupler. Mitochondrial uncouplers insert into the inner mitochondrial membrane and allow hydrogen ions to diffuse through, preventing the accumulation of hydrogen ions outside of the matrix. Turn on the DNP by clicking on the DNP button, it will turn green when on. Run the simulation varying several of the parameters. Explain the mechanisms that would yield these results. Use the simulation to justify why using mitochondrial uncouplers, like DNP, would work as a diet pill.

Simulation: https://exchange.iseesystems.com/public/jon-darkow/cellular-respiration-accounting-model/index.html#page3

Answer 1

Hi Mads S.,

I'd have to agree with you that the simulator doesn't do what you would want it to -- when you turn on the DNP, that doesn't by itself alter the level-vs-time for any of the compounds of interest!

However, you can still reason your way through that -- if the H+ can't emerge into the matrix outside the inner mitochondrial membrane (whatever it's called), then it can't participate in reactions there, such as getting tacked onto NAD to make NADH+. (And O2 can't get reduced, etc., I think that's where that occurs?). So, although the glucose can be burned, the potential chemical energy is wasted, NOT turned into ATP ultimately, which is what you need to have happen. You can see this on the simulation as a sensitivity of O2 consumption and NADH+ production on pH -- up through 8, things are OK, then by 9 everything stops.

By the way, if you haven't already, look up the toxicity effects of DNP. Hyperthermia would not be a fun way to perish!

--Cheers, --Mr. d.