scholarly journals Determining Ideal Balance Among Branched-Chain Amino Acids (BCAA) as a Proof of Concept Study in Healthy Children

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1068-1068
Author(s):  
Haneen Saleemani ◽  
Rajavel Elango ◽  
Gabriella Horvath ◽  
Sylvia Stockler
Keyword(s):  
Protein Synthesis ◽  
Future Research ◽  
Acid Oxidation ◽  
P Value ◽  
Healthy Children ◽  
Proof Of Concept ◽  
Body Protein ◽  
Wide Range ◽  
Medical Foods ◽  
Total Body

Abstract Objectives Medical foods for children with in-born errors of metabolism (propionic academia, PROP) are formulated with imbalanced mixture of the BCAA (high leucine, to minimal or no valine and isoleucine), and therefore their use is controversial. The objective of the current study was to determine an ideal BCAA ratio at which total body protein synthesis is optimized in healthy children using the indicator amino acid oxidation (IAAO) method. Methods The study design was based on the oxidation of the stable isotope L-[1–,13C] phenylalanine to ,13CO2 to compare protein synthesis among seven different BCAA ratios. Leucine intake was gradually reduced from current high doses in medical foods; isoleucine and valine were kept constant. This study was done as a proof of concept in healthy children, to allow characterization of the metabolic responses to wide range of leucine test intakes, to help design narrow BCAA ratio range to test in children with PROP. Results A total of 8 healthy children were studied, completing 42 study days. ANOVA showed significant differences in F13CO2 with different BCAA ratios; P value <0.001. A BCAA ratio of (leucine: Isoleucine: Valine = 1:0:0) was associated with the highest F13CO2 compared to other ratios (p value <0.001), indicating low total body protein synthesis. By reducing leucine intake, with BCAA ratio between (1: 0.26: 0.28 to 1:0.35:0.4) protein synthesis was optimized. Conclusions Using the IAAO method in healthy children, we tested for the first time the effect of different BCAA ratios on protein synthesis. Results from this study confirmed that the BCAA ratio of (leucine: Isoleucine: Valine = 1:0:0), which is similar to the ratio in medical foods, limited total body protein synthesis. Furthermore, a balanced BCAA ratio that optimized protein synthesis was found to be between (1: 0.26: 0.28) and (1: 0.35:0.4). Thus, we propose reformulating the BCAA mixture in medical foods, by reducing leucine content by 50%. Future research in children with PROP with our proposed BCAA ratio is necessary to confirm improved patient growth outcomes. Funding Sources Faculty of Applied Medical Sciences, Department of Clinical Nutrition, King Abdulaziz University and BC Children's Hospital Research Institute.

Protein turnover in the human fetus studied at term using stable isotope tracer amino acids

1993 ◽  
Vol 265 (1) ◽  
pp. E31-E35 ◽  
Author(s):  
P. F. Chien ◽  
K. Smith ◽  
P. W. Watt ◽  
C. M. Scrimgeour ◽  
D. J. Taylor ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Placental Transfer ◽  
Safety Margin ◽  
Whole Body ◽  
Acid Oxidation ◽  
Maternal Circulation ◽  
Body Protein ◽  
Isotope Tracer ◽  
Elective Cesarean

Before elective cesarean delivery (4 h), we infused L-[1-13C]leucine and L-[15N]phenylalanine into the maternal circulation and measured enrichment and concentration of amino acids and carbon dioxide in cord blood of six normal human fetuses at delivery. There were net fetal uptakes of leucine (2.22 +/- 0.29 mumol.kg-1.min-1) and phenylalanine (0.80 +/- 0.11 mumol.kg-1.min-1) with net outputs of CO2 (6.11 +/- 1.12 ml.kg-1.min-1) and the transamination product of leucine, alpha-ketoisocaproate (1.04 +/- 0.32 mumol.kg-1.min-1). Fetal amino acid oxidation accounted for a substantial proportion of the flux from the mother (leucine, 0.36 +/- 0.09 mumol.kg-1.min-1 and phenylalanine, 0.18 +/- 0.04 mumol.kg-1.min-1). Fetal whole body accretion of leucine carbon (0.82 +/- 0.21 mumol.kg-1.min-1) was 69% of the umbilical uptake, and that of phenylalanine (0.62 +/- 0.08 mumol.kg-1.min-1) was 78%. Fetal whole body protein synthesis was approximately 13 g.kg-1.day-1, i.e., much faster than in adults but similar to that in the newborn. Net protein accretion was 2-4 g.kg-1.day-1. The placental supply of leucine and phenylalanine exceeds the fetal demand for protein synthesis by only a small amount, suggesting that the safety margin of placental transfer may be small for these amino acids. The results suggest that the method could be applied safely to studies of fetal growth retardation.

Nephrotic proteinuria has no net effect on total body protein synthesis: Measurements with 13C valine

2000 ◽  
Vol 35 (6) ◽  
pp. 1149-1154 ◽  
Author(s):  
Monique G.M. de Sain-van der Velden ◽  
Kees de Meer ◽  
Wim Kulik ◽  
Christian F. Melissant ◽  
Ton J. Rabelink ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Body Protein ◽  
Nephrotic Proteinuria ◽  
Total Body

scholarly journals The mysteries of nitrogen balance

1999 ◽  
Vol 12 (1) ◽  
pp. 25-54 ◽  
Author(s):  
J. C Waterlow
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Urea Cycle ◽  
N Balance ◽  
Single Amino Acid ◽  
Whole Body ◽  
Acid Oxidation ◽  
Physiological Level ◽  
Body Protein ◽  
Urea Production

AbstractThe first part of this review is concerned with the balance between N input and output as urinary urea. I start with some observations on classical biochemical studies of the operation of the urea cycle. According to Krebs, the cycle is instantaneous and automatic, as a result of the irreversibility of the first enzyme, carbamoyl-phosphate synthetase 1 (EC 6.3.5.5; CPS-I), and it should be able to handle many times the normal input to the cycle. It is now generally agreed that acetyl glutamate is a necessary co-factor for CPS-1, but not a regulator. There is abundant evidence that changes in dietary protein supply induce coordinated changes in the amounts of all five urea-cycle enzymes. How this coordination is achieved, and why it should be necessary in view of the properties of the cycle mentioned above, is unknown. At the physiological level it is not clear how a change in protein intake is translated into a change of urea cycle activity. It is very unlikely that the signal is an alteration in the plasma concentration either of total amino-N or of any single amino acid. The immediate substrates of the urea cycle are NH3 and aspartate, but there have been no measurements of their concentration in the liver in relation to urea production. Measurements of urea kinetics have shown that in many cases urea production exceeds N intake, and it is only through transfer of some of the urea produced to the colon, where it is hydrolysed to NH3, that it is possible to achieve N balance. It is beginning to look as if this process is regulated, possibly through the operation of recently discovered urea transporters in the kidney and colon. The second part of the review deals with the synthesis and breakdown of protein. The evidence on whole-body protein turnover under a variety of conditions strongly suggests that the components of turnover, including amino acid oxidation, are influenced and perhaps regulated by amino acid supply or amino acid concentration, with insulin playing an important but secondary role. Molecular biology has provided a great deal of information about the complex processes of protein synthesis and breakdown, but so far has nothing to say about how they are coordinated so that in the steady state they are equal. A simple hypothesis is proposed to fill this gap, based on the self-evident fact that for two processes to be coordinated they must have some factor in common. This common factor is the amino acid pool, which provides the substrates for synthesis and represents the products of breakdown. The review concludes that although the achievement and maintenance of N balance is a fact of life that we tend to take for granted, there are many features of it that are not understood, principally the control of urea production and excretion to match the intake, and the coordination of protein synthesis and breakdown to maintain a relatively constant lean body mass.

Body composition of harp seals

1994 ◽  
Vol 72 (3) ◽  
pp. 545-551 ◽  
Author(s):  
Rosemary Gales ◽  
Deane Renouf ◽  
Elizabeth Noseworthy
Keyword(s):  
Body Composition ◽  
Body Mass ◽  
Body Fat ◽  
Body Condition ◽  
Total Body Water ◽  
Body Water ◽  
Accurate Estimation ◽  
Body Protein ◽  
Wide Range ◽  
Total Body

Using chemical analysis we measured the composition of 26 harp seals (Phoca groenlandica) representing both sexes, aged between 3 months and 30 years, and encompassing a wide range of body conditions. Predictive relationships between total body water and total body fat contents, total body protein content, and gross energy were calculated. These equations allow accurate estimation of harp seal body composition provided total body water content and body mass are known. Using these data we compared the accuracy of three existing equations that have been used to predict body fat content of other species. We found that in adult harp seals, lean body mass has a relatively stable hydration of 70% but the hydration of blubber varied with body condition. Lipid content, and thus energy density of blubber, increased with increasing body condition.

Administration of testosterone to wether lambs: effects on protein and energy metabolism and growth hormone status

1987 ◽  
Vol 115 (3) ◽  
pp. 439-445 ◽  
Author(s):  
G. E. Lobley ◽  
A. Connell ◽  
V. Buchan ◽  
P. A. Skene ◽  
J. M. Fletcher
Keyword(s):  
Protein Synthesis ◽  
Energy Expenditure ◽  
Vascular System ◽  
Day Treatment ◽  
Anabolic Steroids ◽  
Control Period ◽  
Nitrogen Retention ◽  
Whole Body ◽  
Acid Oxidation ◽  
Body Protein

ABSTRACT The effects of episodic infusion of testosterone into the vascular system on energy expenditure, nitrogen retention and whole body protein synthesis (determined from [1-14C]leucine kinetics) were studied in castrated male lambs under conditions of controlled food intake. Comparisons were made between a 10-day control period and a 10-day treatment period for each lamb. Infusion of testosterone produced a significant increase in heat production, but the magnitude (198 kJ/day, +2·5% was less than the differences in energy expenditure expected between entire and castrated male ruminants. The retention of nitrogen improved by 1·24 g/day ( + 22%) in response to the administration of androgen, and this was accompanied by a decrease in amino acid oxidation. Total protein synthesis also declined, and the anabolic nature of testosterone supply must, therefore, be effected through a reduction in the breakdown of protein, the mechanism being similar to that proposed for certain anabolic steroids and the β-agonist, clenbuterol. Contrary to other reports, the presence of testosterone had no effect on the plasma concentration of GH. J. Endocr. (1987) 115, 439–445

Effect of testosterone on muscle mass and muscle protein synthesis

1989 ◽  
Vol 66 (1) ◽  
pp. 498-503 ◽  
Author(s):  
R. C. Griggs ◽  
W. Kingston ◽  
R. F. Jozefowicz ◽  
B. E. Herr ◽  
G. Forbes ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Total Body Potassium ◽  
Body Protein ◽  
Total Body

We have studied the effect of a pharmacological dose of testosterone enanthate (3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than 0.02); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than 0.0001). In four subjects, a primed continuous infusion protocol with L-[1–13C]leucine was used to determine whole-body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis.

Total Protein Synthesis in Elderly People: A Comparison of Results with [15N]glycine and [14C]leucine

1977 ◽  
Vol 53 (3) ◽  
pp. 277-288 ◽  
Author(s):  
M. H. N. Golden ◽  
J. C. Waterlow
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Specific Radioactivity ◽  
The Elderly ◽  
Synthesis Rate ◽  
Total N ◽  
Body Protein ◽  
Total Body ◽  
Plasma Leucine ◽  
The Individual

1. Total body protein turnover was studied in six elderly patients. 2. During the study they were fed by continuous infusion of a liquid formula through a nasogastric tube. l-[1-14C]Leucine and [15N]glycine were infused at a constant rate for 30 h. The labelled glycine was infused into the intragastric line; the labelled leucine was given either by this route or intravenously. 3. The specific radioactivity of free leucine in plasma and the rate of output of 14CO2 in expired air both reached a plateau at 10 h, and remained constant until the end of the infusion at 30 h. 4. The 15N abundance in urinary urea and total N was very similar. In neither was a plateau reached by 30 h but in four out of the six patients the abundance in urinary NH4+ had attained a plateau by the end of the infusion. 5. Flux rates and rates of protein synthesis were calculated in four ways: (A) from the specific radioactivity of plasma leucine at plateau; (B) from the proportion of dose excreted as 14CO2 at plateau; (C) from the final rates of 15N excretion in urea or total urinary N; (D) from the final or plateau rates of 15N excretion in urinary NH4+. 6. On average, the estimates of synthesis rate obtained by methods B and C agreed closely; those given by methods A and D were lower. Methods A, B and D ranked the individual patients in almost identical order. 7. The comparison of methods makes it possible to examine the validity of the assumptions on which the different methods depend. Method B is probably theoretically the most satisfactory and, of the methods used in this work, probably gives the best estimate of the absolute turnover rate. The other methods can be used for comparative purposes. 8. The results suggest that the rate of protein turnover is reduced in the elderly, compared with younger subjects.

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