Studies of protein metabolism with stable isotopes require determination of the 'natural' isotopic enrichment in tissues. This has previously been determined by taking a pre-test muscle biopsy or by using the isotopic enrichment of a separate control group of subjects. In this study we have measured and compared the 'natural' 13C enrichment of leucine in plasma protein and muscle protein in 14 subjects. The mean enrichment of leucine (delta 13CPDB) in muscle protein, -26.627, was not significantly different from that in plasma protein, -27.152. The data indicate that the 13C enrichment of leucine in plasma protein reflects that of muscle protein and provides an attractive alternative to an additional muscle biopsy in studies of protein metabolism with stable isotopes.
Eighteen patients with localized colorectal carcinoma were randomized to receive intravenous nutrition or to be fasted during the 24 h before surgery. Protein synthesis, an index of tumour growth, was then measured by the incorporation of [13C]leucine into tumour protein immediately before surgery. The mean (s.e.m.) rate of tumour protein synthesis in patients receiving nutrition (42.7(3.5) per cent per day) was 89 per cent higher than the rate in the fasted group (22.6(1.9) per cent per day) (P = 0.002). As tumours consist of a variety of different cell types, in vitro rates of protein synthesis were measured in malignant cells isolated from colorectal tumours and cultured with autologous serum obtained from the patient in either the fasted or the fed state. There was a mean increase of 81 per cent in protein synthesis when fed rather than fasted serum was used (P less than 0.02), indicating that the malignant cells themselves respond to nutrient supply. This increase in tumour protein synthesis provides the first evidence in vivo that the exogenous supply of nutrients can modulate the rate of growth of a human tumour.
1. Rates of protein synthesis have been measured from the incorporation of 57 mg of L-[1-13C]leucine/kg for 90 min into muscle tissue and colorectal tumours removed at surgery from cancer patients. 2. For the 20 h preceding surgery and during the measurement of protein synthesis, the patients received intravenous saline, conventional intravenous nutrition (0.2 g of N and 103 non-protein kJ/kg body weight) or intravenous nutrition enriched with the branched-chain amino acids leucine, isoleucine and valine (0.2 g of N with 30% from branched-chain amino acids and 103 non-protein kJ/kg body weight). 3. Conventional intravenous nutrition resulted in a significant stimulation of the rate of protein synthesis in both muscle tissue (2.64 +/- 0.75%/day versus 1.78 +/- 0.51%/day in saline control, means +/- SD) and tumour tissue (43.9 +/- 10.3%/day versus 22.6 +/- 5.6%/day in saline control). 4. Pre-operative nutrition enriched with branched-chain amino acids was less effective than conventional intravenous nutrition in stimulating protein synthesis in both muscle and tumour. The rates of protein synthesis were 2.12 +/- 0.41%/day in muscle and 33.7 +/- 5.3%/day in the tumours. 5. The expression of proliferating cell nuclear antigen in sections of the tumours showed changes with intravenous feeding of the two different amino acid mixtures that were similar to the changes in protein synthesis, and these two variables were significantly correlated. This is evidence that feeding with conventional mixtures and mixtures enriched with branched-chain amino acids stimulates tumour growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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