Oxidation and metabolic interconversion in malignant cachexia.

Some patients with progressive malignant disease have an increase in basal metabolic expenditure as well as total caloric expenditure, but the findings are neither striking nor consistent. Studies of specific metabolic changes in such patients have shown the following. (a) The predominant substrate for energy in these subjects is fatty acid, as in normal humans. Comparative studies show, however, that greater proportions of the oxidative metabolism in patients with cancer are from fatty acids, particularly when exogenous glucose is available. While the free fatty acid levels in plasma decrease appropriately with glucose administration, current evidence suggests that the levels of free fatty acids themselves may not necessarily be directly related to the various disposal mechanisms. (b) Increased glycolysis and gluconeogenesis are present after overnight fasting in the patients with malignant disease, but these processes, which depend on liver metabolism, are appropriately suppressed with exogenous glucose. (c) Evidence is presented that leucine, an amino acid representative of branched-chain amino acids, is not under normal metabolic control in these subjects. For example, semistarvation does not result in diminished levels of branched-chain amino acids as it does in other patients. Also, glucose does not have its ordinary suppressive effect on branched-chain amino acid levels. Leucine turnover is increased in these patients as is the percentage of leucine flux which is oxidized. Limited data support the oxidation of this amino acid. All these data suggest that the peripheral effects of insulin and glucose may not be normally mediated in these subjects. They also suggest that amino acid metabolism and consequently protein metabolism may be unaffected by normal control factors in malignant disease.