Cancer cachexia demonstrates the energetic impact of gluconeogenesis in human metabolism

A review-based hypothesis is presented on the energy flow in cancer patients. This hypothesis centres on the hypoxic condition of tumours, the essential metabolic consequences, especially the gluconeogenesis, the adaptation of the body, and the pathogenesis of cancer cachexia. In growing tumours the O-2 concentration is critically tow. Mammalian cells need O-2 for the efficient oxidative dissimilation of sugars and fatty acids, which gives 38 and 128 motes of ATP per mote glucose and palmitic acid, respectively. In the absence of sufficient O-2 they have to switch to anaerobic dissimilation, with only 2 motes of ATP and 2 motes of lactic acid from 1 mote of glucose. Since mammalian cells cannot ferment fatty acids, in vivo tumour cells completely depend on glucose fermentation. Therefore, growth of these tumour cells wilt require about 40 times more glucose than it should require in the presence of sufficient O-2.Since lactic acid lowers the intracellular pH, it decreases the activity of pyruvate dehydrogenase, stimulates fermentation, and thus amplifies its own fermentative production. Compensatory glucose is provided by hepatic gluconeogenesis from tactic acid. However, the liver must invest 3 times more energy to synthesize glucose than can be extracted by tumour cells in an anaerobic way. The liver extracts the required energy from amino acids and especially from fatty acids in an oxidative way. This may account for weight loss, even when food intake seems adequate. In the liver 6 motes of ATP are invested in the gluconeogenesis of one mote of glucose. The energy content of 4 out of these 6 motes of ATP is dissipated as heat. This may account for the elevated body temperature and sweating experience by cancer patients. (c) 2006 Elsevier Ltd. All rights reserved.