Branched-Chain Amino Acids, Nitrogen Excretion and Injury in Man

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.

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.5.7481 ◽

2001 ◽

Vol 86 (5) ◽

pp. 2136-2143 ◽

Cited By ~ 1

Author(s):

Zhenqi Liu ◽

Linda A. Jahn ◽

Wen Long ◽

David A. Fryburg ◽

Liping Wei ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Ribonucleic Acid ◽

Nitrogen Excretion ◽

Phenylalanine Concentration ◽

Messenger Ribonucleic Acid ◽

Plasma Phenylalanine ◽

Branched Chain ◽

Urinary Nitrogen Excretion ◽

Urinary Nitrogen

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.

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17 Challenges and implications of feeding diets with excess concentrations of leucine to growing-finishing pigs

Journal of Animal Science ◽

10.1093/jas/skaa054.026 ◽

2020 ◽

Vol 98 (Supplement_3) ◽

pp. 16-16

Author(s):

Mike D Tokach ◽

Henrique S Cemin ◽

Hayden R Kerkaert ◽

Jason C Woodworth ◽

Steve S Dritz ◽

...

Keyword(s):

Amino Acids ◽

Blood Meal ◽

Meta Analysis ◽

Branched Chain Amino Acids ◽

Nitrogen Excretion ◽

Intact Protein ◽

Future Research ◽

Distillers Grains With Solubles ◽

Diet Formulation ◽

Branched Chain

Abstract Excess dietary leucine stimulates the key enzymes involved in branched-chain catabolism causing breakdown of all branched-chain amino acids, including isoleucine and valine. Branched-chain amino acids share a common brain transporter with other large neutral amino acids (LNAA). Excess levels of one of the LNAA increases brain uptake of that amino acid and decreases the uptake of the other LNAA, including tryptophan. Thus, excess leucine can impact the requirements for many amino acids. From a practical basis, this effect was first demonstrated with diets containing blood meal, but was thought to be of limited concern unless high blood meal diets were fed. Use of corn dried distillers grains with solubles (DDGS) or high protein DDGS in corn-based diets results in diets containing excess leucine. These high leucine levels are of limited concern if adequate levels of other branched-chain amino acids and LNAA are fed, which is often the case if the diet consists largely of intact protein sources. Feed grade amino acids, such as L-lysine, L-threonine, L-tryptophan, DL-methionine, L-valine, and L-isoleucine have been widely adopted as a means to lower nitrogen excretion and diet cost. Including these amino acids in diets containing corn products reduces dietary leucine; but the resulting diets are formulated near the requirement for the first 6 limiting amino acids, including valine, isoleucine, and tryptophan, while still being high in leucine. The excess leucine increases the requirements for valine, isoleucine, and possibly other LNAA, such as tryptophan and possibly others. The exact relationship between these amino acids and how to handle them in practical diet formulation is still being elucidated; however, recent meta-analysis and experimental data confirm the importance of these ratios and provide useful direction for future research.

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A Comparison of the Effects of Intravenous Infusion of Individual Branched-Chain Amino Acids on Blood Amino Acid Levels in Man

Clinical Science ◽

10.1042/cs0600095 ◽

1981 ◽

Vol 60 (1) ◽

pp. 95-100 ◽

Cited By ~ 51

Author(s):

S. Eriksson ◽

L. Hagenfeldt ◽

J. Wahren

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Intravenous Infusion ◽

Serum Insulin ◽

Aromatic Amino Acids ◽

Branched Chain Amino Acids ◽

Blood Concentrations ◽

Branched Chain Amino Acid ◽

Amino Acid Levels ◽

Branched Chain

1., Intravenous infusions of l-valine (600 μmol/min), l-isoleucine (150 μmol/min), l-leucine (300 μmol/min) and a mixture of the three branched-chain amino acids (70% l-leucine, 20% l-valine, 10% l-isoleucine; 270 μmol/min) were given to four groups of healthy volunteer subjects. Whole-blood concentrations of amino acids and glucose and serum insulin were measured before and during the infusions. 2. Valine and isoleucine infusions resulted in twelve- and six-fold increases in the respective amino acid. During valine infusion, tyrosine was the only amino acid for which a decrease in concentration was seen (25%, P < 0.05). With isoleucine administration, no significant changes were found. In contrast, leucine infusion (during which the leucine concentration rose about sixfold) was accompanied by significant decreases in tyrosine (35%), phenylalanine (35%), methionine (50%), valine (40%) and isoleucine (55%). The arterial glucose concentration fell slightly (5%) and the insulin concentration increased 20% during leucine infusion. 3. Infusion of the mixture of the three branched-chain amino acids resulted in marked decreases in tyrosine (50%), phenylalanine (50%) and methionine (35%). The decreased amino acid levels remained low for 2 h after the end of the infusion. 4. The present findings demonstrate that intravenous infusion of leucine (not infusion of valine or isoleucine) results in marked reductions in the concentrations of the aromatic amino acids and methionine. Infusion of a mixture of the three branched-chain amino acids gives results similar to those obtained with leucine infusion alone. Thus a mixed branched-chain amino acid solution with leucine as its main constituent seems to be the best alternative in the treatment of patients with hepatic cirrhosis and encephalopathy.

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BLOOD BRANCHED-CHAIN AMINO AND α-KETO ACID CONCENTRATIONS AND NET EXCHANGE ACROSS THE PORTAL-DRAINED VISCERA AND HINDLIMB OF FED AND FASTED RUMINANTS

Canadian Journal of Animal Science ◽

10.4141/cjas87-106 ◽

1987 ◽

Vol 67 (4) ◽

pp. 1011-1020 ◽

Cited By ~ 3

Author(s):

RICHARD J. EARLY ◽

JAMES R. THOMPSON ◽

ROBERT J. CHRISTOPHERSON ◽

GARY W. SEDGWICK

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Hind Limb ◽

Venous Blood ◽

Branched Chain Amino Acids ◽

Keto Acid ◽

Branched Chain Amino Acid ◽

Keto Acids ◽

Branched Chain ◽

Cattle And Sheep

In the first of two experiments, whole blood branched-chain amino acid (BCAA) and plasma branched-chain α-keto acid (BCKA) concentrations in jugular venous blood were determined in cattle and sheep before and during a 6-d fast. In cattle, concentrations of valine, isoleucine, α-ketoisovalerate (KIV) and α-ketomethylvalerate (KMV) remained unchanged whereas leucine and α-ketoisocaproate (KTC) increased (P < 0.05) during fasting. In sheep, only KIV and KMV remained unchanged whereas BCAA and KIC increased (P < 0.05) during fasting. In a second experiment on cattle chronically catheterized to measure BCAA and BCKA exchange across the portal-drained viscera (PDV) and hindlimb (HL), the PDV added and the HL removed BCAA from the blood of fed cattle. The opposite exchange occurred after a 6-d fast. Releases of BCKA from the PDV and HL in both fed and fasted states were small compared to BCAA exchanges. The data suggest that blood BCAA but not BCKA concentrations may respond differently to starvation in sheep versus cattle and that in cattle the PDV and HL do not release appreciable amounts of BCKA relative to the net movements of the BCAA. Key words: Portal-drained viscera, hind limb, branched-chain amino acids, branched-chain α-keto acids, fasting, ruminants

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Utilization of amino acids by preruminant lambs. I. The effect of alterations in total essential amino acid intake at constant nitrogen intake

Australian Journal of Agricultural Research ◽

10.1071/ar9770917 ◽

1977 ◽

Vol 28 (5) ◽

pp. 917 ◽

Cited By ~ 1

Author(s):

H Dove ◽

GR Pearce ◽

DE Tribe

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Nitrogen Balance ◽

Control Diet ◽

Essential Amino Acids ◽

Conclusive Evidence ◽

Metabolizable Energy ◽

Nitrogen Excretion ◽

Urinary Nitrogen Excretion ◽

Urinary Nitrogen

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.

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Effect on Urinary Nitrogen Excretion of Rate of Administration of Solution of Amino Acids in Man

Experimental Biology and Medicine ◽

10.3181/00379727-79-19387 ◽

1952 ◽

Vol 79 (3) ◽

pp. 382-384 ◽

Cited By ~ 2

Author(s):

C. S. Davidson ◽

R. D. Eckhardt

Keyword(s):

Amino Acids ◽

Nitrogen Excretion ◽

Urinary Nitrogen Excretion ◽

Urinary Nitrogen

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Only L-valine among branched-chain amino acids is effective in promoting the growth of the small intestinal mucosa

Gastroenterology ◽

10.1016/s0016-5085(01)83364-3 ◽

2001 ◽

Vol 120 (5) ◽

pp. A676-A676

Author(s):

T TAKAHASHI ◽

H DOI ◽

H KOMATSU ◽

K SATO ◽

O UEDA ◽

...

Keyword(s):

Amino Acids ◽

Intestinal Mucosa ◽

Branched Chain Amino Acids ◽

Small Intestinal Mucosa ◽

Small Intestinal ◽

Branched Chain

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The Weight Loss Effects of Branched Chain Amino Acids and Vitamin B6: A Randomized Controlled Trial on Obese and Overweight Women

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000511 ◽

2018 ◽

Vol 88 (1-2) ◽

pp. 80-89 ◽

Cited By ~ 3

Author(s):

Zahra Shakibay Novin ◽

Saeed Ghavamzadeh ◽

Alireza Mehdizadeh

Keyword(s):

Amino Acids ◽

Weight Loss ◽

Body Composition ◽

Vitamin B6 ◽

Controlled Trial ◽

Density Lipoprotein ◽

Branched Chain Amino Acids ◽

Model Assessment ◽

Waist To Hip Ratio ◽

Branched Chain

Abstract. Branched chain amino acids (BCAA), with vitamin B6 have been reported to improve fat metabolism and muscle synthesis. We hypothesized that supplementation with BCAA and vitamin B6 would result in more weight loss and improve body composition and blood markers related to cardiovascular diseases. Our aim was to determine whether the mentioned supplementation would affect weight loss, body composition, and cardiovascular risk factors during weight loss intervention. To this end, we performed a placebo-controlled randomized clinical trial in 42 overweight and obese women (BMI = 25–34.9 kg/m2). Taking a four-week moderate deficit calorie diet (–500 kcal/day), participants were randomized to receive BCAA (6 g/day) with vitamin B6 (40 mg/day) or placebo. Body composition variables measured with the use of bioelectrical impedance analysis, homeostatic model assessment, and plasma insulin, Low density lipoprotein, High density lipoprotein, Total Cholesterol, Triglyceride, and fasting blood sugar were measured. The result indicated that, weight loss was not significantly affected by BCAA and vitamin B6 supplementation (–2.43 ± 1.02 kg) or placebo (–1.64 ± 1.48 kg). However, significant time × treatment interactions in waist to hip ratio (P = 0.005), left leg lean (P = 0.004) and right leg lean (P = 0.023) were observed. Overall, supplementation with BCAA and vitamin B6 could preserve legs lean and also attenuated waist to hip ratio.

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