Leucine metabolism in patients with malignant disease

Studies of the metabolism of the amino acid, leucine, have been carried out in six patients with progressive cancer and compared to similar studies in a group of control subjects. U-14C leucine was given by the single injection technique and the disappearance of radioactive leucine from the plasma as well as the appearance of the label in expired air was determined over a 3-hour interval in both the overnight fasting state and during glucose ingestion. Plasma leucine levels in the basal state were higher in the patients with malignant disease (193 +/- 17 mumol/L vs 135 +/- 16 mumol/L) as was the flux or rate of appearance of unlabeled leucine molecules into the plasma (136 +/- 5 mumol/kg hour vs 79 mumol/kg/hour). Oxidation of leucine resulted in the appearance of about 19% of the injected label in expired CO2 of control subjects with almost twice that amount being found in progressive cancer patients. When the irreversible disposal of leucine to a metabolic fate other than oxidation was calculated (perhaps an indicator of protein synthesis), this was also increased in the progressive cancer patients. Exogenous glucose administration resulted in a fall in both leucine level and flux in the control subjects, while these parameters were less affected in three of the cancer patients. The fall in oxidation when glucose was given was more pronounced in the control subjects. These data are interpreted to mean that all aspects of leucine metabolism, presumably an example of branched chain amino acid metabolism, appear to be accelerated in subjects with cancer and weight loss. In addition, the peripheral control of the metabolism of this group of amino acids, as affected by glucose and insulin, appears to be impaired.