Cachexia, gluconeogenesis and progressive weight loss in cancer patients

Abstract

Several theories have been proposed to account for the pathogenesis of cachexia in cancer patients. One of these is that the tumor's greater avidity for essential amino acids can result in an amino acid imbalance, which in turn can cause cachexia. In this paper it is shown how, by known biochemical mechanisms, a tumor caused amino acid imbalance can lead to cachexia, progressive weight loss, abnormal gluconeogenesis and lactate recycling. Cachexia leads to a decreased dietary intake, but the cachectic cancer patient, unlike normal man, is unable to adapt. The reason is that the changeover of metabolic fuels from the fed state (glucose) to the starved state (lipids) is hormone regulated, but gluconeogenesis and lactate recycling are substrate regulated. Because of this substrate regulation of gluconeogenesis, the host will be unable to effectively decrease gluconeogenesis as long as the tumor persists in causing an amino acid imbalance.