Reference no: EM133475842
Problem
What Should Connor Do?
DNP (2,4-dinitrophenol) inserts into the inner mitochondrial membrane and shuttles protons between the intermembrane space and the matrix. The energy released as the protons move down their concentration gradient is dissipated as heat. This is manifested physiologically by a rise in body temperature (a fever). Without the protein gradient, ATP synthase is not able to maintain ATP production.
The mitochondrion tries to adjust its ATP production by increasing the rate of glycolysis and burning more energy reserves (fats). The energy from the fat burning is used to pump protons to the inter membrane space. However, as long as DNP is in the membrane, this is a futile effort as many of the protons flow back into the matrix. This is how DNP works as a weight-loss drug. It uncouples the energy derived from the breakdown of fats and sugars (which pumps protons to the matrix) from the production of ATP.
DNP is but one known mitochondrial uncoupler. Acetylsalicylic acid (Aspirin) and the drug 3,4-methylenedioxyN-methamphetamine (MDMA, or ecstasy) are also mitochondrial uncouplers. In human cells, there are also proteins (called UCPs-uncoupling proteins) that can uncouple the breakdown of sugars and fats from the synthesis of ATP. Variant forms of these proteins have been linked with obesity.
In the course of his web research, Connor encounters a 2006 report of two people dying as a consequence of DNP use. "Surely, they wouldn't be able to sell DNP online if it were dangerous. I'll bet they had another condition."
But the report in the Journal of Analytical Toxicology states that "Death in both cases was attributed to 2,4-DNP toxicity" (Miranda et al., 2006).
Task
Question 1. Based on your understanding of the mechanism of action of DNP presented here, how dangerous do you think DNP really is?
Question 2. For an athlete, what are the consequences of ATP depletion?
Question 3. Should Connor take DNP to lose weight?
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