In the past, the uncoupler 2,4-dinitrophenol was used as a weight-reducing drug until side effects such as fatigue and breathlessness precluded its use. How could the use of this drug result in weight loss?
ExplanationUncouplers such as 2,4-dinitrophenol dissociate oxidation from phosphorylation. Thus, ADP is not phosphorylated to produce ATP and respiration becomes uncontrolled as it tries to replenish ATP supplies. This leads to increased metabolic turnover (as in fat oxidation) in the attempt to generate ATP. Less ADP will be converted to ATP, causing increased ADP and increased rates of oxidative phosphorylation. Prolonged energy deficits will lead to fatigue in energy-dependent tissues such as muscle or heart (cardiomyopathy), the latter being potentially lethal.
