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.