Altered leucine metabolism in noncachectic sarcoma patients

Leucine and whole body protein metabolism were quantitated in 26 human subjects (6 sarcoma patients, 20 age-matched normal controls) using a primed, continuous infusion of [13C]leucine. Plasma samples were analyzed every 15 min for enrichment of [13C]leucine. Plateau enrichment levels were then used to calculate whole-body protein turnover, synthesis, and breakdown rates. Exhaled gas samples were analyzed every 15 min for enrichment of 13CO2, and plateau enrichment levels (as well as CO2 production rates) were used to calculate leucine oxidation rates. Fasting plasma amino acid levels, serum albumin, and total protein levels were also determined. The 6 patients were otherwise healthy but had a large, localized high-grade sarcoma which had not been previously treated. No patient had weight loss. Amino acid, albumin, and total protein levels were equivalent in patients and controls. Whole-body protein turnover rates were significantly greater in sarcoma patients than age-matched controls (15%). Increased protein turnover rates resulted in increased whole-body protein synthesis and breakdown rates in sarcoma patients compared to controls. Leucine oxidation rates were not different in the 2 groups. The results suggest that in humans with high-grade sarcomas leucine metabolic abnormalities are specific to tumor growth and not malnutrition because abnormalities of turnover, synthesis, and breakdown occur prior to any weight loss or measurable change in blood amino acid or protein level.