scholarly journals Branched Chain Amino Acids Activate Messenger Ribonucleic Acid Translation Regulatory Proteins in Human Skeletal Muscle, and Glucocorticoids Blunt This Action1

2001 ◽  
Vol 86 (5) ◽  
pp. 2136-2143 ◽  
Author(s):  
Zhenqi Liu ◽  
Linda A. Jahn ◽  
Wen Long ◽  
David A. Fryburg ◽  
Liping Wei ◽  
...  

Branched chain amino acids (BCAA) are particularly effective anabolic agents. Recent in vitro studies suggest that amino acids, particularly leucine, activate a signaling pathway that enhances messenger ribonucleic acid translation and protein synthesis. The physiological relevance of these findings to normal human physiology is uncertain. We examined the effects of BCAA on the phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (eIF4E-BP1) and ribosomal protein S6 kinase (p70S6K) in skeletal muscle of seven healthy volunteers. We simultaneously examined whether BCAA affect urinary nitrogen excretion and forearm skeletal muscle protein turnover and whether the catabolic action of glucocorticoids could be mediated in part by inhibition of the action of BCAA on the protein synthetic apparatus. BCAA infusion decreased urinary nitrogen excretion (P < 0.02), whole body phenylalanine flux (P < 0.02), plasma phenylalanine concentration (P < 0.001), and improved forearm phenylalanine balance (P = 0.03). BCAA also increased the phosphorylation of both eIF4E-BP1 (P < 0.02) and p70S6K (P < 0.03), consistent with an action to activate the protein synthetic apparatus. Dexamethasone increased plasma phenylalanine concentration (P < 0.001), prevented the BCAA-induced anabolic shift in forearm protein balance, and inhibited their action on the phosphorylation of p70S6K. We conclude that in human skeletal muscle BCAA act directly as nutrient signals to activate messenger ribonucleic acid translation and potentiate protein synthesis. Glucocorticoids interfere with this action, and that may be part of the mechanism by which they promote net protein catabolism in muscle.

1976 ◽  
Vol 50 (5) ◽  
pp. 393-399 ◽  
Author(s):  
J. H. Wedge ◽  
R. De Campos ◽  
A. Kerr ◽  
R. Smith ◽  
Rose Farrell ◽  
...  

1. Venous blood concentrations of the branched-chain amino acids, valine, leucine and isoleucine, and urinary nitrogen excretion have been measured in sixteen adult males, from 2 h to 7 days after injury, and in four adults after elective skin grafts. 2. In the injured group the concentrations of these amino acids rose significantly 24 h after injury and had doubled at 4 days and remained high; in contrast the skin-graft patients showed no significant change. 3. In those injured patients with initial hyperketonaemia, defined as more than 0·2 mmol/l, the increase in concentrations of branched-chain amino acids at the fourth and seventh days after injury was significantly less than in those with normoketonaemia, and was accompanied by lower urinary nitrogen excretion throughout the whole period. 4. It is suggested that the changes in the concentration of branched-chain amino acids after injury indicate decreased uptake by muscle or excessive release due to an imbalance between protein synthesis and protein catabolism in this tissue.


1977 ◽  
Vol 28 (5) ◽  
pp. 917 ◽  
Author(s):  
H Dove ◽  
GR Pearce ◽  
DE Tribe

Male crossbred lambs weighing 12.5 kg (period 1), 20 kg (period 2) and 30 kg (period 3) were infused per abomasum with milk-based diets in which crude protein (CP) and energy contents were constant at a given Iiveweight, but in which the proportion of CP supplied as essential amino acids (EAA) varied from 120 to 876 g EAA/kg CP. Responses in liveweight gain, nitrogen balance and metabolizable energy (ME) intake (period 1 only) were measured. A number of lambs died while receiving diets containing very high or very low proportions of EAA. Possible reasons for these deaths are discussed. In all periods liveweight gains were greatest in lambs given the control diet (513 g EAA/kg CP). In period 1 this liveweight gain was close to that expected on the basis of energy intake, but in periods 2 and 3, liveweight gains on the control diets were less than anticipated. Reductions in liveweight gain were greater for diets containing low proportions of EAA than those containing high proportions. The infusion of diets containing low proportions of EAA markedly increased urinary nitrogen excretion. The effect of diets containing high proportions was less pronounced. As a result of these effects, lambs given the control diet had the highest daily nitrogen balance in all periods. Nitrogen balance was less severely affected by the dietary changes than liveweight gain, particularly with 30 kg lambs. It is suggested that the reduced retention of apparently digested nitrogen in diets other than the control diets reflected the unsuitability of the pattern of absorbed amino acids for protein synthesis. The effect of diet on the components of energy balance in period 1 was less pronounced than its effect on nitrogen balance. The metabolizability of apparently digested energy was lower in diets other than the control diet, especially those containing low proportions of EAA. This is attributed to the energy cost of increased urinary nitrogen excretion on such diets. Alternative interpretations of the results are discussed, and it is suggested that dietary amino acids will be utilized most efficiently for protein synthesis by the tissues of the lamb when essential and non-essential amino acids are provided in approximately equal proportions. There was no conclusive evidence that this optimum proportion was different for older lambs.


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Pierre Singer ◽  
Itai Bendavid ◽  
Ilana BenArie ◽  
Liran Stadlander ◽  
Ilya Kagan

Abstract Background and aims Combining energy and protein targets during the acute phase of critical illness is challenging. Energy should be provided progressively to reach targets while avoiding overfeeding and ensuring sufficient protein provision. This prospective observational study evaluated the feasibility of achieving protein targets guided by 24-h urinary nitrogen excretion while avoiding overfeeding when administering a high protein-to-energy ratio enteral nutrition (EN) formula. Methods Critically ill adult mechanically ventilated patients with an APACHE II score > 15, SOFA > 4 and without gastrointestinal dysfunction received EN with hypocaloric content for 7 days. Protein need was determined by 24-h urinary nitrogen excretion, up to 1.2 g/kg (Group A, N = 10) or up to 1.5 g/kg (Group B, N = 22). Variables assessed included nitrogen intake, excretion, balance; resting energy expenditure (REE); phase angle (PhA); gastrointestinal tolerance of EN. Results Demographic characteristics of groups were similar. Protein target was achieved using urinary nitrogen excretion measurements. Nitrogen balance worsened in Group A but improved in Group B. Daily protein and calorie intake and balance were significantly increased in Group B compared to Group A. REE was correlated to PhA measurements. Gastric tolerance of EN was good. Conclusions Achieving the protein target using urinary nitrogen loss up to 1.5 g/kg/day was feasible in this hypercatabolic population. Reaching a higher protein and calorie target did not induce higher nitrogen excretion and was associated with improved nitrogen balance and a better energy intake without overfeeding. PhA appears to be related to REE and may reflect metabolism level, suggestive of a new phenotype for nutritional status. Trial registration 0795-18-RMC.


1976 ◽  
Vol 27 (1) ◽  
pp. 139 ◽  
Author(s):  
JG Mulholland ◽  
JB Coombe ◽  
WR McManus

Individually penned Border Leicester x Merino wethers, aged 11 months, were fed ad lib. for 16 weeks on a basal ration of ground, pelleted oat straw, urea and minerals, supplemented with 0, 5, 10, 15, 20, 30 or 40% starch. The diets contained equal percentages of nitrogen and minerals. Dry matter intake reached a maximum of 2000 g/day with 30% starch; above this starch level, digestive disturbances were observed. Organic matter digestibility was increased by the addition of starch, but cellulose digestibility was depressed by as much as 18 units with the addition of 30% starch. Up to 10% the starch level had little effect on cellulose digestibility. Liveweight change was significantly correlated with digestible organic matter intake, mean daily weight gains varying from 22 g with no starch to 104 g with 30% starch. However, a large percentage of the liveweight gain was as total body water, and body energy storage increased appreciably only when the diet contained at least 20% starch. The inclusion of 5% starch slightly depressed both intake and liveweight gain. Daily clean wool production was significantly increased at starch levels higher than 20% and ranged from 5.3 to 7.5 g/day with 0 and 40% starch respectively. Increasing levels of starch had little effect on apparent nitrogen digestibility, but resulted in a substantial increase in nitrogen retention through a reduction in urinary nitrogen excretion. Serum urea levels fell from a mean of 42 mg/100 ml during the first week to 31 mg/100 ml during subsequent periods, with no significant differences between diets. With the general exception of potassium, mineral balances were positive or close to zero throughout the experiment.


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