Table 1. Effect of Path on energetics of oxidation
Thyrotoxicosis
Thyroid hormone decreases efficiency possibly by mechanisms involving both uncoupling and cycling described above: oxidative uncoupling as well as increased futile cycling of intermediates [15]. It is observed in thyrotoxic mice that UCP1 decreases efficiency in brown fat at the mitochondrial level [8]. In humans, the role of UCP1 in thyrotoxicosis is less certain due to the relative paucity of brown fat. On the other hand, activation of the adrenergic system via phosphoenolpyruvatecarboxykinase ultimately increases "futile" metabolic cycling of intermediates ([15]). Thyrotoxicosis is well known to result in weight loss, often with increased food intake and increased generation of heat, indicative of metabolic inefficiency. The use of thyroid hormone has even been suggested therapeutically to induce weight loss in obese individuals, although its toxicity has limited this application. Inefficiency in metabolic processes with weight loss and increased heat generation, therefore, is known to occur on clinical grounds. Even without a complete understanding of the relative importance of different underlying cellular mechanisms in humans, the potential for biochemical processes to reduce their efficiency must be considered established as a feature of mammalian metabolism.