1. The short-term effect of oral feeding on albumin synthesis rate was investigated in 12 healthy volunteers using two meal regimens. Albumin synthesis was measured over 90 min after injection of a ‘flooding’ amount (43 mg/kg body weight) of phenylalanine enriched to 7.5, 10 or 15 atoms% with the stable isotope [ ring - 2 H 5 ]phenylalanine. 2. In one set of subjects, consumption of five small hourly meals resulted in a consistent and significant increase ( P < 0.05) in albumin fractional synthesis rate from a mean (± SEM) fasting value of 5.8 (± 0.4)%/day to 7.1 (± 0.4)%/day in the fed state. 3. A second study in which albumin synthesis was measured 30 min after consumption of a single larger meal was carried out in another set of volunteers. The fractional rate of albumin synthesis was again significantly elevated after feeding ( P < 0.05), rising from 7.1 (± 0.4)%/day in the fasted state to 9.1 (± 0.6)%/day in the fed state. In both studies, similar responses were observed in the absolute rate of albumin synthesis (mg day −1 kg −1 ). 4. Albumin secretion time was significantly shorter ( P < 0.05) after feeding in both studies, suggesting that the acute stimulation in albumin synthesis observed after feeding may in part be mediated via a post-transcriptional mechanism. 5. The response of total liver protein synthesis to oral feeding was investigated in an animal model employing adult rats studied with a flooding amount of [2,6- 3 H]phenylalanine. 6. The results indicated a stimulation of 20% with no difference in the proportion of albumin synthesis relative to total liver synthesis, determined from the immunoprecipitation of albumin from the liver.

1 Rates of protein synthesis have been measured from the incorporation of 57 mg of l-[1- 13 C]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. 6. In this study the mixture enriched with branched-chain amino acids provided no clear advantage for cancer patients, since a smaller response to branched-chain amino acids was observed in both tumours and host muscle tissue.

1. The rate of protein synthesis in quadriceps muscle of healthy subjects estimated from the incorporation of l -[1- 13 C]leucine given by continuous infusion was 1.1%/day. The estimate of protein synthesis from the incorporation of a flooding amount of labelled leucine was 1.8%/day ( sd 0.65). The possibility that the higher rate obtained with the flooding technique arose from stimulation of protein synthesis by the large amount of leucine is unlikely. 2. The same rate of protein synthesis (1.7%/day, sd 0.3) was obtained with a flooding amount (0.05 g/kg) of a different amino acid, l -[1- 13 C]phenylalanine, as was obtained with leucine. 3. Incorporation of l -[1- 13 C]phenylalanine was not affected by simultaneous injection of leucine (1.7%/day, sd 0.7) or valine (1.6%/day, sd 0.4). 4. Protein synthesis, assessed in a completely different way from the proportion of polyribosomes isolated from the skeletal muscle, was unaltered by the injection of 0.05 g of l -leucine/kg (44.6%, sd 8.5 versus 43.8%, sd 7.7). 5. Good agreement in estimates of protein synthesis was observed in subjects in whom both legs were measured with both l -[1- 13 C]leucine (mean difference 0.16%/day) and l -[1- 13 C]phenylalanine (mean difference 0.2%/day).

1. A method is described for measuring the rates of protein synthesis in vivo in human colorectal and breast tumours by the intravenous injection of l -[1- 13 C]leucine as a ‘flooding dose'. 2. The incorporation of isotope into colorectal tumour protein was measured in six patients, whose tumours were biopsied after the injection. Fractional rates of protein synthesis were calculated from the enrichment of leucine in protein and the average free leucine enrichment in plasma. The range of rates obtained was 17.2–33.9%/day, with a mean rate (± sem ) of 22.5 ± 2.6%/day. 3. Tumour protein synthesis rates were also measured in 15 patients with breast cancer. The range of rates obtained was 5.3–15.9%/day, with a mean rate (± sem ) of 10.3 ± 0.8%/day. These rates are significantly lower than those obtained with colorectal tumours ( P < 0.001). 4. In 9 of the breast cancer patients, protein synthesis was measured in multiple random biopsies taken from the same tumour. The mean (± sem ) difference between the highest and lowest rates in biopsies from the same tumour was only 1.1 ± 0.3%/day. Only 13% of the variation in protein synthesis between separate tumours could be explained by sampling error because of variation within the tumour itself, the remainder being genuine variation between individual tumours.

1. Rates of protein synthesis were measured, in vivo , in lung, liver, heart and skeletal muscle of young male rats. Groups of rats were exposed for 1 h duration to one of the following anaesthetic regimens: 1.4% halothane, 2.2% halothane, 1.4% halothane in 66% nitrous oxide, intravenous pentobarbitone (20 mg/kg) and intravenous midazolam (18 mg/kg) combined with fentanyl (2 μg/kg). Fractional rates of protein synthesis were determined by injecting [ 3 H]phenylalanine (150 μmol/100 g body weight) 2. Liver protein synthesis was depressed significantly by all regimens, except midazolam/fentanyl, by up to 37.7% of control values. Lung protein synthesis was significantly reduced by all the anaesthetic agents by up to 30% of control rates 3. The effects of the anaesthetic agents on skeletal muscle and heart were small and not statistically significant 4. There was no evidence of ventilatory depression as manifested by changes in arterial blood gas partial pressures of CO 2 and O 2 , except in the group treated with 2.2% halothane.

1. Protein synthesis was measured in muscle of fed and fasted rats. Synthesis rates were 29% higher with feeding. Treatment with indomethacin before feeding completely blocked the stimulation of protein synthesis. 2. Whole-body protein synthesis was measured in six healthy volunteers with [ 15 N]glycine in fasted and fed states. Feeding increased synthesis rates by 50%. An oral dose of indomethacin 2 h before the measurement of protein synthesis had no effect in either the fasted or fed state.

1. Twenty-two children were studied as in-patients at a Nigerian Hospital. 2. They were divided into four groups on the basis of weight for age: I, adequately nourished, acutely infected; II, moderately under weight, acutely infected; III, malnourished, chronically infected; IV, malnourished, uninfected. 3. Urinary nitrogen excretion was highest in group I and lowest in groups III and IV. Urinary creatinine was highest in group I, but did not differ significantly in groups II, III and IV. The excretion of 3-methylhistidine closely paralleled that of creatinine. It is suggested that the high rates of creatinine and methylhistidine excretion in group I resulted in part from destruction of muscle. 4. Rates of whole body protein turnover were measured by administration of a single dose of [ 15 N]glycine with measurement of the excretion of 15 N in urinary NH 3 for the next 9 h. 5. Rates of protein synthesis and breakdown were very high in infected children of groups I and II. Although rates were lower in the malnourished groups, in infected children of group III they were nearly twice as high as in the uninfected group IV. The net balance of protein (synthesis minus breakdown) was negative in group I, less negative in group II, zero in group III and positive in group IV. 6. Repeat measurements in group I during recovery from infection showed a decline in rates of excretion of nitrogen, creatinine and 3-methylhistidine. Rates of protein synthesis and breakdown declined and the protein balance became less negative, but these changes were not statistically significant. 7. Multiple regression analysis of the results of all groups taken together showed independent contributions to rates of protein metabolism from infection and nutritional state, especially plasma albumin. 8. It was concluded that infection caused a rise in protein breakdown which was larger than the concomitant rise in synthesis, leading to net loss of protein, and that these responses were reduced by malnutrition.

1. The rate of whole-body nitrogen flux; protein synthesis and protein breakdown were measured in patients with colorectal cancer (Dukes A—C) just before and 12 weeks after surgical removal of the tumour. The rates were determined from the urinary excretion of 15 N in ammonia and in urea over a 9 h period after an oral dose of [ 15 N]glycine. 2. The food intake during the 2 study days was identical for individual patients. The amount each received was determined from measurement of their intake of food ad libitum on the day preceding the pre-operative study and was consumed in six equal portions every 2 h during the experimental period. 3. No significant differences in the rates of nitrogen flux, protein synthesis and protein breakdown were found before and after tumour resection, whether calculated from the excretion of 15 N in ammonia or in urea. Some changes in flux, both increases and decreases, were observed in individual patients after tumour removal but these could not be related to classification of the tumour, or to the presence of pre-operative anorexia or weight loss. 4. The results suggest that the primary tumour itself does not alter the overall rate of protein metabolism in the whole body.

1. Four normal adults were given [ 15 N]-glycine in a single dose either orally or intravenously. Rates of whole-body protein turnover were estimated from the excretion of 15 N in ammonia and in urea during the following 9 h. The rate derived from urea took account of the [ 15 N]urea retained in body water. 2. In postabsorptive subjects the rates of protein synthesis given by ammonia were equal to those from urea, when the isotope was given orally, but lower when an intravenous dose was given. 3. In subjects receiving equal portions of food every 2 h rates of synthesis calculated from ammonia were much lower than those from urea whether an oral or intravenous isotope was given. Comparison of rates obtained during the post-absorptive and absorptive periods indicated regulation by food intake primarily of synthesis when measurements were made on urea, but regulation primarily of breakdown when measurements were made on ammonia. 4. These inconsistencies suggest that changes in protein metabolism might be assessed better by correlating results given by different end-products, and it is suggested that the mean value given by urea and ammonia will be useful for this purpose.

1. Six men were infused intravenously for 10 h with a tracer amount of l-[U- 14 C]tyrosine while on a standardized food intake. 2. Measurements of plasma l-[ 14 C]-tyrosine specific radioactivity and the excretion rate of 14 CO 2 were made at frequent intervals and showed plateau labelling of plasma and expired carbon dioxide within 6–8 h. The tyrosine flux was calculated from the specific radioactivity in plasma at plateau value. 3. The excretion rate of 14 CO 2 , corrected for retention of label within the bicarbonate pool, showed that oxidation accounted for 20% of the tyrosine flux. Urinary excretion of label was negligible. 4. Rates of protein synthesis were calculated from the flux of tyrosine after subtracting the proportion oxidized. Although the mean rate of synthesis was consistent with other measurements of protein turnover, the individual values ranged from 284 to 387 g/day. The variation was not reduced by relating turnover to body weight, lean body mass or energy expenditure. 5. Estimating the rates of protein breakdown from the tyrosine flux involved some assumptions about pathways of phenylalanine metabolism. The use of a labelled essential amino acid would therefore give more accurate values for short-term measurements of whole body protein turnover.