2,4-Dinitrophenol (Don't mess with the mitochondria)

Fundamental to learning how energy is moved around in biology is understanding ATP equivalents. You've probably heard about how ATP is "the energy currency of life" - and rightly so; every mole of ATP hydrolyzed is equivalent to about 10 kcals. Bioenergetics isn't really a direct food-to-ATP transaction, though. One crucial part of the indirect dance that is bioenergetics is called oxidative phosphorylation. Here, some molecules (NADH and FADH2) that constitute the business end of a lot of the enzymes responsible for oxidation reactions get regenerated (becoming NAD+ and FAD).

Still following? This explains that we regenerate FAD and NAD+, but not why it matters in energy terms. As this transfer of oxidizing equivalents is occuring in the mitochondrion (a substructure within the cell), a "proton gradient" is formed. That is, there are more protons on one side of the membrane than the other (in other words, one side is more acidic). Having a chemical gradient is a lot like being atop a hill - that is, we have some potential energy to work with. The cell makes good use of such gradients to (finally!) make some ATP. This is ultimately how the oxygen you get from air helps you net the energy from your food.

For these reasons, the transfer of oxidizing equivalents is crucial to bioenergetics - the overwhelming majority of the energy you get from metabolizing a molecule of glucose comes via this indirect mechanism (only 2 of the >30 ATP equivalents you get in glycolysis are generated directly!)

So you might imagine you tinker with such a mechanism at your own peril. You'd be right. Poisoning the mitochondria is a pretty good way to kill something - cyanide and carbon monoxide, for example, throw a wrench in this particular system of electron transfer. Nobody's taking cyanide willingly - no, wait, they are. Some people go absolutely crazy for the stuff as a quack cancer treatment.

Cancer often being such a desperate situation, some people will try anything. More baffling are the people who tinker with the electron transport chain with known-to-be-dangerous compounds for reasons of vanity:


2,4-dinitrophenol will pretty effectively collapse that proton gradient that all those NADH and FADH2 molecules helped generate. Since a hydrophobic membrane separates the high- and low-proton concentration sides of the gradient, the protons cannot cross this membrane very easily (except when being used to generate some ATP). The lipophilic 2,4-DNP, however, will move through the membrane with facility, shuttling protons down the gradient along the way. It does this for free, too - you don't get any ATP out of the deal! The proton gradient is converted into heat. Effectively having a severed fuel line, a DNP-dosed subject will burn many calories (and run a fever) just to keep up with basic ATP requirements.

It can cause one to lose weight like crazy. For a time, it was present in diet pills. There is a pro-drug subculture in sport, particularly bodybuilding, that still uses the compound today (presumably obtained from industrial and fine chemical type sources). It is not safe. See, for example, here and here.


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I have also seen HF used as a homeopathic remedy against, wait for it male pattern baldness. I thought I would fall of my chair because the one time I have seen it used is when a particularly bad stain was on one of our NMR tubes and undergrad used it while in the fume hood, dressed up in gloves that came up to his elbows and a rubber apron, and there my father was with a small vial of "super diluted" HF that was supposed to help him with his hairloss.

Reading your final 'not safe' link, the 2006 study, I notice the second in the "Related" list is a study on toxicity of dibutyl phthalate, one of the extremely widely used plasticizers.

Why would this chemical be considered a 'related' item, do you know?