[Glutamine--a non-essential but important amino acid].
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Critical Care↗
Biomedical subjects
J Wernerman
Publications and source records attributed to J Wernerman.
Long-term changes in muscle free amino acid levels after elective abdominal surgery.
Characteristic changes in the pattern of muscle free amino acids are seen on the third day after elective surgery. The time course of the restoration to normal levels in uncomplicated cases has not been established before. Seven metabolically healthy patients undergoing cholecystectomy were studied. Muscle biopsy specimens and plasma samples were taken before operation and on days 3, 10, 20 and 30 after surgery. The level of total free amino acids in skeletal muscle decreased and the concentrations of branched chain and aromatic amino acids increased on day 3. The original levels were found to be restored on day 10 after surgery. A decrease in glutamine of 38 per cent (P less than 0.001) was seen on day 3, of 20 per cent (P less than 0.05) on day 10 and of 22 per cent (P less than 0.05) on day 30, compared with preoperative values. These results constitute a baseline for future studies in which the impact of nutritional and pharmacological therapies is to be evaluated beyond the immediate postoperative period.
Amino Acids↗
Biosynthetic human growth hormone preserves both muscle protein synthesis and the decrease in muscle-free glutamine, and improves whole-body nitrogen economy after operation.
As a reproducible human trauma model, patients (n = 17) undergoing elective cholecystectomy were studied for 3 postoperative days. They were randomly allocated to receive either recombinant human growth hormone (hGH; 0.3 U/kg/24 hours) or placebo together with total parenteral nutrition, including 0.2 gN/kg/24 hours and 135 kJ/kg/24 hours. Before operation and on the third postoperative day, percutaneous muscle biopsies were performed to determine the concentration and size distribution of ribosomes and the free amino acid concentrations. The significant postoperative decrease in the total ribosome concentration (15.3 +/- 6.4%) and the polyribosome concentration (20.9 +/- 6.5%) in the control group was impeded in the group receiving synthetic hGH. Muscle free glutamine decreased by 35.6 +/- 4.2% in the control group and to a lesser extent in the group that was given hGH after operation (p less than 0.05). The protein content of skeletal muscle was unchanged. The cumulated nitrogen balance for the study period was negative in the control group (-7.09 +/- 0.71 gN), but was not different from zero in the hGH group (-2.32 +/- 1.66 gN). It is concluded that synthetic hGH administered after operation has beneficial effects on the whole-body nitrogen economy, as indicated by the unchanged capacity for protein synthesis in skeletal muscle, the preserved levels of muscle free glutamine, and improvement in the whole-body nitrogen balance. The effects of hGH on skeletal muscle protein and amino acid metabolism can explain the postoperative nitrogen-sparing effect attributed to hGH.
Adult↗
Free amino acids in plasma and muscle during 24 hours post-operatively--a descriptive study.
Intracellular amino acids in skeletal muscle show a specific concentration pattern on the third post-operative day. The temporal development of these changes has not been clarified. Here the amino acid concentrations in skeletal muscle were studied during the first post-operative day in fourteen patients undergoing elective abdominal surgery. Muscle amino acids were determined pre-operatively, as well as at 12 and 24 h post-operatively. In muscle the concentrations of glutamine and the basic amino acids decreased gradually during the first 24 h after surgery to 79% (P less than 0.001) and 67% (P less than .001) respectively. The sum of the essential amino acids decreased to 73% (P less than 0.001) at 12 h, but thereafter rose to 91% (P less than 0.05) at 24 h. The sum of the BCAA decreased to 84% (P less than 0.05) at 12 h but then increased to 116% (P less than 0.05) at 24 h. The alanine concentration increased to 122% (P less than 0.001) during the first post-operative day. In plasma the alanine concentration increased at 12 h while most other amino acids declined. At 24 h post-operatively the plasma concentrations of all amino acids had returned to normal or showed a tendency towards normalization except for phenylalanine, which increased. At the end of the first post-operative day the concentrations of amino acids in muscle were consistent with the alterations previously observed three days after surgery. The changes in plasma amino acid concentrations only partly reflected those in muscle.
Amino Acids↗
Short-term starvation decreases skeletal muscle protein synthesis rate in man.
The rate of protein synthesis in skeletal muscle was determined in the post-absorptive state and after 3 days of starvation in healthy volunteers. The flooding dose technique employing intravenous injection of (1-13C)leucine (0.05 g kg-1) was used and incorporation of isotope into muscle protein was measured by taking percutaneous biopsies at 0 and 90 min. Blood samples were taken during the incorporation period for assessment of the enrichment of the free amino acid precursor of protein synthesis. The median (25,75 quartiles) rate of muscle protein synthesis after an overnight fast was 2.03 (2.00,2.23) % days-1 when the precursor enrichment was obtained by measurement of the plasma alpha-ketoisocaproate, taken to be representative of muscle free leucine. Repeat measurements in the same subjects after 3 days of total starvation showed a decrease to 1.82 (1.57,2.05) % days-1. Rates calculated on the basis of the plasma leucine as precursor were 5% lower at both times. An interindividual variation in response to starvation was observed, but the median decrease of 13% in the rate of protein synthesis was statistically significant (P less than 0.01).
Adult↗
Uncomplicated surgery, but not general anesthesia, decreases muscle protein synthesis.
The impact of anesthesia and surgery on protein metabolism is not well characterized. The single effect of general anesthesia and the combined effects of surgery and general anesthesia on protein synthesis in skeletal muscle were studied in metabolically healthy patients (n = 14) undergoing elective abdominal surgery. The rate of muscle protein synthesis was calculated from the increase in enrichment of [1-13C]leucine in protein during 90 min after an intravenous infusion of [1-13C]leucine (0.05 g/kg, 20 atom percent excess). The 1-13C enrichments of plasma leucine and plasma alpha-ketoisocaproate were used to indicate the enrichment of muscle free leucine. The protein synthesis rate was unaffected by general anesthesia; however, at the end of surgery, a 31.5% decline was seen from 2.19(2.13,2.33)%/24 h before anesthesia to 1.50(1.21,1.77)%/24 h (P less than 0.05) immediately after cholecystectomy while the patients were still under general anesthesia.
Anesthesia, General↗
Amino acid concentrations in plasma and skeletal muscle after transurethral resection syndrome.
The concentrations of amino acids in plasma and skeletal muscle were measured 1 and 4 hours after transurethral prostatic resection in three patients who developed symptoms of the transurethral resection syndrome. The irrigating solution contained 1.5% of glycine and 1% of ethanol. The concentrations of glycine in plasma and muscle were equal within an hour of the operation, and at four hours the abnormally high glycine concentration persisted in muscle, though it had decreased rapidly in plasma. Our data suggest that skeletal muscle is a quantitatively important reservoir for glycine when this amino acid is supplied in potentially toxic amounts, but that the plasma glycine concentration returns to normal as the patient's clinical condition improves.
Acid-Base Equilibrium↗
Effects of insulin on myocardial uptake of branched chain amino acids soon after cardiac operations.
Infusion of insulin-glucose-potassium is used to support the failing heart after cardiac operations. Although the effects on myocardial uptake of carbohydrates and lipids have been described, the effects on myocardial extraction of amino acids are unknown. This study was undertaken to clarify the effect of insulin-glucose-potassium on the pattern of amino acid uptake/release in myocardial and skeletal muscle after coronary operations. The amino acid uptake/release of the heart and of the leg was studied in 18 patients 1 hour after coronary bypass operations. The patients were randomized to treatment with 25 U of fast-acting insulin as a bolus injection followed by a continuous infusion of 1 U/kg body weight for 1 hour, or to serve as control patients. The hyperinsulinemic "clamp" technique was used to keep blood glucose unchanged during the study. In the insulin-treated group, the arterial concentration of 17 of 22 individual amino acids, including the three branched chain amino acids, decreased, the remainder being unchanged. The amino acid uptake/release of the leg was unchanged. The net myocardial uptake of leucine and isoleucine shifted to a no-uptake/no-release in the insulin-treated group, whereas the no-uptake/no-release of tyrosine and phenylalanine turned into a significant release. A positive correlation was observed between arterial concentration and myocardial uptake/release of the three branched chain amino acids. It is suggested that insulin, by lowering the arterial concentration of leucine and isoleucine, inhibited the myocardial uptake of these amino acids. This may have a negative effect on postoperative myocardial protein balance suggested by the release of tyrosine and phenylalanine.
Amino Acids, Branched-Chain↗
Stimulation of protein synthesis in human tumours by parenteral nutrition: evidence for modulation of tumour growth.
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.
Aged↗
Growth hormone improves muscle protein metabolism and whole body nitrogen economy in man during a hyponitrogenous diet.
Healthy male volunteers (n = 12) were given a normocaloric hyponitrogenous diet for a conditioning period of 7 days. Thereafter they were blindly randomized to receive daily injections of methionyl recombinant human growth hormone (met-hGH) 0.06 IU/kg or saline during a second week of hyponitrogenous nutrition. The met-hGH group showed a lower urinary urea excretion and a lower serum concentration of urea as compared with the control group. In skeletal muscle, the polyribosome concentration, indicative of muscle protein synthesis, as well as the concentrations of glutamine, alanine, aspartate, serine, and threonine, decreased in the control group, whereas no such changes were seen in the met-hGH-treated group. Since provision of met-hGH prevented protein catabolism in muscle and improved whole body nitrogen economy, investigations of the possible beneficial effects of met-hGH to prevent skeletal muscle vast after surgical trauma are advocated.
Amino Acids↗
Ribosome and free amino acid content in muscle during hemodialysis.
Patients (N = 8) with chronic renal failure and uremia treated with hospital hemodialysis were in a pilot study investigated before and after a single hemodialysis session. The extracorporeal dialysis circuit was flushed regularly with saline to avoid clotting and the use of heparin. Percutaneous skeletal muscle biopsies were taken before and after the dialysis to determine the content of free amino acids together with the concentration and size distribution of ribosomes before and after dialysis. After dialysis the alanine concentration in muscle decreased by 20% (P less than 0.05), while all other amino acids were unaffected. The total ribosome concentration per mg of DNA decreased by 31% (P less than 0.01) and the relative proportion of polyribosomes by 7% (P less than 0.05) after the dialysis compared to predialytic values. All individual plasma amino acids decreased during the dialysis procedure except for threonine and arginine, which were unaltered, and leucine and isoleucine, which increased. The decline in ribosome and polyribosome content together with the changes in amino acid levels indicate a low capacity for protein synthesis and increased catabolism in muscle of hemodialyzed patients.
Adolescent↗
Measurement of protein synthesis in human skeletal muscle: further investigation of the flooding technique.
1. The rate of protein synthesis in quadriceps muscle of healthy subjects estimated from the incorporation of L-[1-13C]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-[1-13C]phenylalanine, as was obtained with leucine. 3. Incorporation of L-[1-13C]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-[1-13C]leucine (mean difference 0.16%/day) and L-[1-13C]phenylalanine (mean difference 0.2%/day).
Adult↗
Organ-specific measurements of protein turnover in man.
Methods that were originally developed for animal studies have now been modified for measuring tissue protein turnover in man with stable isotopes. Of the three techniques which have been discussed, only the arterio-venous difference method has the capacity to measure both the synthesis and degradation. This technique is, however, difficult to perform and has a number of potential sources of error, one of the most important being the assessment of precursor labelling. Constant infusion of a labelled amino acid with measurement of the incorporation into protein of a biopsy is a simpler and more precise technique for measuring synthesis in patients as well as volunteers, but the most appropriate means of assessing the precursor labelling still remains to be worked out. The flooding-dose procedure aims to minimize the difficulty of assessing precursor labelling and there is no evidence that the unphysiological dose of labelled amino acid given influences the synthesis rate which is measured. It is rapid to perform and is very well suited to measurements in patients, in whom a wide range of tissues can be studied. These advances in techniques have been facilitated particularly by improvements in mass spectrometry, which have allowed the use of stable in place of radioactive isotopes, and have enabled measurements of isotopic enrichments to be made in small samples of tissue. These techniques for assessing the dynamics of protein metabolism in individual tissues are now being used to answer nutritionally and clinically important questions in human volunteers and patients.
Amino Acids↗
Alpha-ketoglutarate preserves protein synthesis and free glutamine in skeletal muscle after surgery.
Serving as a reproducible human trauma model, patients (n = 21) undergoing elective cholecystectomy received postoperative total parenteral nutrition with (n = 9) or without (n = 12) alpha-ketoglutarate (AKG) supplementation. Skeletal muscle biopsy specimens were taken before surgery and on the third postoperative day. The postoperative decreases in the concentrations of free glutamine and basic amino acids seen in the control group were counteracted in the AKG group (p less than 0.05). Muscle protein synthesis was estimated by ribosome analysis. On the third postoperative day the control group showed a decline in the polyribosome concentration (25.8% +/- 4.5%; p less than 0.001). No significant change was observed in the AKG group. On each postoperative day the nitrogen balance was negative in the control group but not in the AKG group. In the control group the cumulative nitrogen balance amounted to -9.9 +/- 1.8 gm of nitrogen and in the AKG group -2.6 +/- 2.6 gm of nitrogen, which was significantly different (p less than 0.05). Administration of AKG, the carbon skeleton corresponding to glutamine, produced results similar to those seen when glutamine is added to postoperative total parental nutrition. The results suggest that the availability of precursors for glutamine synthesis in skeletal muscle is crucial for the degree of muscle protein catabolism after surgical trauma.
Adult↗
Alpha-ketoglutarate and postoperative muscle catabolism.
The hypothesis that muscle protein catabolism after trauma is associated with a shortage of alpha-ketoglutarate, rather than glutamine, was tested. Addition of alpha-ketoglutarate to postoperative total parenteral nutrition prevented the decrease in muscle protein synthesis and free glutamine that usually occurs after surgery. alpha-ketoglutarate supplementation may improve recovery after trauma.
Cholecystectomy↗
Effects of an amino acid solution enriched with either branched chain amino acids or ornithine-alpha-ketoglutarate on the postoperative intracellular amino acid concentration of skeletal muscle.
Patients undergoing elective cholecystectomy provide a highly reproducible model of the effects of trauma on intermediary metabolism. Three parenteral nutrition regimens were given to groups of eight such patients. An isonitrogenous total parenteral nutrition, including a commercially available amino acid solution, an amino acid solution enriched with branched chain amino acids or one supplemented with ornithine-alpha-ketoglutarate, was given after operation. The intra cellular free amino acid concentrations of skeletal muscle were determined in tissue specimens obtained before operation and on the third postoperative day using a percutaneous needle biopsy technique. The mean (s.e.m.) decrease in the concentrations of free intracellular glutamine on the third postoperative day was less pronounced (P less than 0.05) in the ornithine-alpha-ketoglutarate group (18.8(7.5)per cent) than in the control group (39.4(5.1)per cent) or the branched chain amino acid group (45.3(6.1)per cent). In conclusion, in the immediate postoperative period total parenteral nutrition supplemented with ornithine-alpha-ketoglutarate countered the decline in the muscle free glutamine. No difference in this parameter was seen between the control group and the branched chain amino acid group.
Amino Acids↗
Elective abdominal surgery depresses muscle protein synthesis and increases subjective fatigue: effects lasting more than 30 days.
Ten patients without metabolic disease undergoing elective cholecystectomy were studied before surgery and on days 3, 10, 20 and 30 after operation. Percutaneous muscle biopsies were taken and protein synthesis was determined from the total concentration and size distribution of ribosomes. The subjective feeling of fatigue was estimated using a visual analogue scale. The nitrogen balance was calculated at 20 days following surgery. The mean (s.e.m.) total concentration of ribosomes per milligram of DNA decreased by 27.5(6.6) per cent (P less than 0.01), 44.5(6.5) per cent (P less than 0.001), 48.3(8.9) per cent (P less than 0.001) and 45.0(8.2) per cent (P less than 0.01) on days 3, 10, 20 and 30, respectively. By 30 days after surgery no sign of restoration of normality was seen. The relative proportion of polyribosomes had decreased by 20.4(6.4) per cent (P less than 0.05) on the third postoperative day and by 20.4(3.9) per cent (P less than 0.01) on the tenth postoperative day and was restored to the preoperative level by day 20. The subjective fatigue score increased after operation and five of nine patients had not regained their preoperative scores 30 days after surgery. The daily nitrogen balance was negative for 5 days. The cumulated nitrogen losses were not restored until after 18 days following surgery. Elective abdominal surgery caused a sustained depression of protein synthesis for over 30 days, a longer period than previously presumed. These results show that long-term follow-up is required when the effect of different postoperative nutritional regimens are to be evaluated.
Cholecystectomy↗
Trauma metabolism and the heart: studies of heart and leg amino acid flux after cardiac surgery.
Flux of plasma amino acids was measured across the heart and the leg (reflecting mainly skeletal muscle) in 18 patients 1 hour after completion of aorto-coronary bypass surgery. There was a net loss of amino acids from the leg (-324.9 +/- 39 nmol/min/100 ml tissue) while amino acid flux across the heart was not statistically different from zero. There were however positive intertissue correlations between leg and myocardial flux of tyrosine and most other amino acids, suggesting that protein metabolism of both tissues were affected in the same catabolic direction by the trauma response. Alanine and glutamine accounted for 50% of the amino acid release from the leg, which is in accordance with observations in association with other types of trauma. Alanine and glutamine also dominated amino acid release from the heart. Glutamate and aspartate were taken up by both tissues. The principal difference between the tissues was a myocardial uptake of leucine and isoleucine, in contrast to a leg release.
Adult↗