5. The molecule 2,4 dinitrophenol (DNP) was once sold as a diet drug, because of

Question

5. The molecule 2,4 dinitrophenol (DNP) was once sold as a diet drug, because of its ability to increase catabolism and therefore induce weight Ho loss. Unfortunately, in large quantities it can cause death, often due to fatal hyperthermia (high fevers). We now know that DNP serves as an ionophore, an agent that can shuttle protons across biological membranes NO NO a) What are the thermodynamic issues involved in moving an ion across a membrane? b) In what organelle/which membrane would this occur? c) Explain how such an agent might work inside of the cell, leading to the observed weight loss and death

Explanation / Answer

a) biological membranes are made up of phospholipids, which are ampipathic molecules consisting of a hydrophobic tail and a polar head. In a lipid bilayer, hydrophobic tails are burried in the interior of the membranes and polar heads face the aqueous phase. For crossing the hydrophobic core of the bilayer, ions have to leave its hydration shell which is energetically unfavourable and has a high activation energy barrier. Hence membrane are impermeable to charged species.

b) It occurs in the inner mitochondrial membrane.

c) DNP dissipiates the proton gradient across the inner mitochondrial membrane, by leaking protons through it. This bypasses the ATP synthase and hence uncouples ATP synthesis and the energy of proton gradient is dissipiated as heat. As a result, more fuels are catabolised to compensate for the energy inefficiency and to maintain ATP levels. Thus more fats are burned for this leading to weight reduction.

Excess dose of DNP leads to excess heat production during uncoupling and causes hyperthermia, that can be fatal.

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