2,4-Dinitrophenol (DNP) affects electron transport and oxidative phosphorylation

Question

2,4-Dinitrophenol (DNP) affects electron transport and oxidative phosphorylation in mitochondria by binding to H ions in the intermembrane space, and then, because the 2,4-Dinitrophenol is nonpolar, and diffusing with the Ht ion across the mitochondrial membrane into the cytosol. Explain why the pH in the intermembrane space increases after ingesting DNP. You may draw a diagram if it helps your explanation a. b. People who ingest this compound can suffer from fatigue. Explain all of the changes that would occur in the electron transport chain and oxidative phosphorylation after ingesting DNP and describe why these changes could lead to fatique. After DNP was discovered in the 1930's it was used as a dieting drug until it was taken off the market after too many people suffered severe side effects and some died. DNP, however, continues to be used by some body builders because it results in a rapid loss of fat. How does this drug, which affects cell respiration, result in a rapid loss of fat? Think about our discussion in class about how cell respiration is related to other catabolic and anabolic reaction pathways. c.

Explanation / Answer

DNP (Dinitrophenol) is an inhibitor of oxidative phosphorylation. It does not inhibit any of the components of the electron transport chain. However, it increases the fluidity of the inner mitochondrial membrane for protons. So, protons easily diffuse through the inner mitochondrial membrane thereby dissipating the proton gradient created by NADH and FADH2. Hence it results in the uncoupling of proton gradient from oxidative phosphorylation. Due to this property, it is called an uncoupler.

Since the diffusion of protons into the inter membranal space increases, the pH in the inter membranal space decreases after DNP treatment.

pH = -log[H+]

It was used as a therapeutic to reduce weight as energy(ATP) is not produced by the NADH and FADH2. It was discontinued later due to several reasons such as the production of excess heat in the body.

People using DNA suffer from fatigue as aerobic respiration does not produce much energy. SO, they have to depend on limited energy sources. Hence they fatigue quickly.

Fatty acid oxidation produces Acetyl CoA which generates NADH and FADH2 via TCA cycle. Since these molecules cannot synthesize ATP via oxidative phosphorylation in the presence of DNP, there will be rapid degradation of fats in the body.

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