Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism

1998 ◽  
Vol 274 (5) ◽  
pp. E801-E807 ◽  
Author(s):  
Dominique Darmaun ◽  
Susan Welch ◽  
Annie Rini ◽  
Brenda K. Sager ◽  
Astride Altomare ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
De Novo ◽  
Oral Treatment ◽  
Healthy Adults ◽  
Whole Body ◽  
Dependent Manner ◽  
Glutamine Concentration ◽  
Body Protein ◽  
Healthy Humans ◽  
Appearance Rate

The present study was designed to determine whether sodium phenylbutyrate (ΦB) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g ⋅ kg−1 ⋅ day−1) of ΦB were administered for 24 h before study: postabsorptive plasma glutamine concentration declined in a dose-dependent manner, achieving an ≈25% decline for a dose of 0.36 g ΦB ⋅ kg−1 ⋅ day−1. A second group of six healthy adults received 5-h infusions ofl-[1-14C]leucine andl-[1-13C]glutamine in the postabsorptive state on two separate days: 1) under baseline conditions and 2) after 24 h of oral treatment with ΦB (0.36 g ⋅ kg−1 ⋅ day−1) in a randomized order. The 24-h phenylbutyrate treatment was associated with 1) an ≈26% decline in plasma glutamine concentration from 514 ± 24 to 380 ± 15 μM (means ± SE; P < 0.01 with paired t-test) with no change in glutamine appearance rate or de novo synthesis; 2) no change in leucine appearance rate (Ra), an index of protein breakdown (123 ± 7 vs. 117 ± 5 μmol ⋅ kg−1 ⋅ h−1; not significant); 3) an ≈22% rise in leucine oxidation (Ox) from 23 ± 2 to 28 ± 2 μmol ⋅ kg−1 ⋅ h−1( P < 0.01), resulting in an ≈11% decline in nonoxidative leucine disposal (NOLD = Ra − Ox), an index of protein synthesis, from 100 ± 6 to 89 ± 5 μmol ⋅ kg−1 ⋅ h−1( P < 0.05). The data suggest that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a “glutamine trap” to create a model of glutamine depletion; 2) a moderate decline in plasma glutamine does not enhance rates of endogenous glutamine production; and 3) a short-term depletion of plasma glutamine decreases estimates of whole body protein synthesis.

Effects in vivo of decreased plasma and intracellular muscle glutamine concentration on whole-body and hindquarter protein kinetics in rats

1999 ◽  
Vol 96 (6) ◽  
pp. 639-646 ◽  
Author(s):  
Steven W. M. OLDE DAMINK ◽  
Ivo DE BLAAUW ◽  
Nicolaas E. P. DEUTZ ◽  
Peter B. SOETERS
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Whole Body ◽  
Glutamine Supplementation ◽  
Constant Infusion ◽  
Glutamine Concentration ◽  
Protein Kinetics ◽  
Body Protein

Glutamine is considered to be a ‘conditionally’ essential amino acid. During situations of severe stress like sepsis or after trauma there is a fall in plasma glutamine levels, enhanced glutamine turnover and intracellular muscle glutamine depletion. Under these conditions, decreased intramuscular glutamine concentration correlates with reduced rates of protein synthesis. It has therefore been hypothesized that intracellular muscle glutamine levels have a regulatory role in muscle protein turnover rates. Administration of the glutamine synthetase inhibitor methionine sulphoximine (MSO) was used to decrease glutamine levels in male Wistar rats. Immediately after the MSO treatment (t = 0 h), and at t = 6 h and t = 12 h, rats received intraperitoneal injections (10 ml/100 g body weight) with glutamine (200 mM) to test whether this attenuated the fall in plasma and intracellular muscle glutamine. Control animals received alanine and saline after MSO treatment, while saline was also given to a group of normal rats. At t = 18 h rats received a primed constant infusion of l-[2,6-3H]phenylalanine. A three-pool compartment tracer model was used to measure whole-body protein turnover and muscle protein kinetics. Administration of MSO resulted in a 40% decrease in plasma glutamine and a 60% decrease in intracellular muscle glutamine, both of which were successfully attenuated by glutamine infusions. The decreased intracellular muscle glutamine levels had no effect on whole-body protein turnover or muscle protein kinetics. Also, glutamine supplementation did not alter these parameters. Alanine supplementation increased both hindquarter protein synthesis and breakdown but the net balance of phenylalanine remained unchanged. In conclusion, our results show that decreased plasma and muscle glutamine levels have no effect on whole-body protein turnover or muscle protein kinetics. Therefore, it is unlikely that, in vivo, the intracellular muscle concentration of glutamine is a major regulating factor in muscle protein kinetics.

The metabolic consequences of critical illness: acute effects on glutamine and protein metabolism

1999 ◽  
Vol 276 (1) ◽  
pp. E163-E170 ◽  
Author(s):  
N. C. Jackson ◽  
P. V. Carroll ◽  
D. L. Russell-Jones ◽  
P. H. Sönksen ◽  
D. F. Treacher ◽  
...  
Keyword(s):  
Critical Illness ◽  
Whole Body ◽  
Control Group ◽  
Metabolic Clearance ◽  
Glutamine Concentration ◽  
Protein Loss ◽  
Body Protein ◽  
Appearance Rate ◽  
Catabolic State ◽  
Major Increase

Net protein loss and large decreases in plasma glutamine concentration are characteristics of critical illness. We have used [2-15N]glutamine and [1-13C]leucine to investigate whole body glutamine and leucine kinetics in a group of critically ill patients and matched healthy controls. Glutamine appearance rate (Ra,Gln) was similar in both groups. However, in the patients, the proportion of Ra,Gln arising from protein breakdown was higher than in the control group (43 ± 3 vs. 32 ± 2%, P < 0.05). Glutamine metabolic clearance rate (MCR) was 92 ± 8% higher ( P < 0.001), whereas plasma glutamine concentration was 38 ± 5% lower ( P < 0.001) than in the control group. Leucine appearance rate (whole body proteolysis) and nonoxidative leucine disposal (whole body protein synthesis) were 59 ± 14 and 49 ± 15% higher in the patients ( P < 0.001). Leucine oxidation and MCR were increased in the patients by 104 ± 37 and 129 ± 39%, respectively ( P < 0.05). These results demonstrate that critical illness is associated with a major increase in protein turnover. The acute decrease in plasma glutamine concentration and the unaltered plasma Ra,Gln suggest that the increase in proteolysis is insufficient to meet increased demand for glutamine in this severe catabolic state.

Whole-Body Protein Turnover and Hepatic Protein Synthesis Are Increased by Vaccination in Man

1995 ◽  
Vol 89 (4) ◽  
pp. 389-396 ◽  
Author(s):  
M. Cayol ◽  
I. Tauveron ◽  
F. Rambourdin ◽  
J. Prugnaud ◽  
P. Gachon ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Acute Phase ◽  
Protein Metabolism ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Constant Infusion ◽  
Mild Stress ◽  
Phase Reaction ◽  
Body Protein ◽  
Healthy Humans

1. The ability of diphtheria—tetanus—poliomyelitis—typhoid vaccination to induce modifications in protein metabolism was investigated in post-absorptive healthy humans. 2. Seven subjects were studied before and 2 days after vaccination. They underwent an intravenous primed constant infusion of l-[1-13C]leucine for 4 h. Plasma protein concentrations, whole-body amino acid fluxes and acute-phase protein synthesis were determined. 3. Plasma concentrations of fibrinogen, α1-acid glycoprotein, haptoglobin and α1-antitrypsin were significantly elevated 2 days after vaccination (P < 0.05). Leucine oxidation was unaffected but whole-body protein synthesis and breakdown were both increased (P < 0.05), by 25 and 16% respectively, in subjects who had an elevated body temperature (n = 5). Albumin synthesis was unchanged, but hepatic synthesis of fibrinogen was 56% higher after vaccination. 4. The present investigation indicates that diphtheria—tetanus—poliomyelitis—typhoid vaccination could induce a sustained acute-phase reaction. Moreover, protein metabolism appeared to be extremely sensitive to a mild stress since leucine kinetics and fibrinogen synthesis were affected. Therefore, diphtheria—tetanus—poliomyelitis—typhoid vaccination might represent an attractive model for studying the inflammatory process in humans.

scholarly journals Effect of dietary protein on energy metabolism including protein synthesis in the spiny lobster Sagmariasus verreauxi

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuangyao Wang ◽  
Chris G. Carter ◽  
Quinn P. Fitzgibbon ◽  
Basseer M. Codabaccus ◽  
Gregory G. Smith
Keyword(s):  
Protein Synthesis ◽  
Energy Metabolism ◽  
Dietary Protein ◽  
Spiny Lobster ◽  
Ammonia Excretion ◽  
Metabolic Energy ◽  
Whole Body ◽  
Body Protein ◽  
Energy Substrate ◽  
Sagmariasus Verreauxi

AbstractThis is the first study in an aquatic ectotherm to combine a stoichiometric bioenergetic approach with an endpoint stochastic model to explore dietary macronutrient content. The combination of measuring respiratory gas (O2 and CO2) exchange, nitrogenous (ammonia and urea) excretion, specific dynamic action (SDA), metabolic energy substrate use, and whole-body protein synthesis in spiny lobster, Sagmariasus verreauxi, was examined in relation to dietary protein. Three isoenergetic feeds were formulated with varying crude protein: 40%, 50% and 60%, corresponding to CP40, CP50 and CP60 treatments, respectively. Total CO2 and ammonia excretion, SDA magnitude and coefficient, and protein synthesis in the CP60 treatment were higher compared to the CP40 treatment. These differences demonstrate dietary protein influences post-prandial energy metabolism. Metabolic use of each major energy substrate varied at different post-prandial times, indicating suitable amounts of high-quality protein with major non-protein energy-yielding nutrients, lipid and carbohydrate, are critical for lobsters. The average contribution of protein oxidation was lowest in the CP50 treatment, suggesting mechanisms underlying the most efficient retention of dietary protein and suitable dietary inclusion. This study advances understanding of how deficient and surplus dietary protein affects energy metabolism and provides approaches for fine-scale feed evaluation to support sustainable aquaculture.

Effect of dietary protein on bed-rest-related changes in whole-body-protein synthesis

1990 ◽  
Vol 52 (3) ◽  
pp. 509-514 ◽  
Author(s):  
C A Stuart ◽  
R E Shangraw ◽  
E J Peters ◽  
R R Wolfe
Keyword(s):  
Protein Synthesis ◽  
Dietary Protein ◽  
Bed Rest ◽  
Whole Body ◽  
Body Protein

scholarly journals Comprehensive assessment of post-prandial protein handling by the application of intrinsically labelled protein in vivo in human subjects

2021 ◽  
pp. 1-9
Author(s):  
Jorn Trommelen ◽  
Andrew M. Holwerda ◽  
Philippe J. M. Pinckaers ◽  
Luc J. C. van Loon
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Stable Isotope ◽  
Dietary Protein ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Human Subjects ◽  
Whole Body ◽  
Body Protein

All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.

Contribution of Skin to Whole-Body Protein Synthesis in Rats at Different Stages of Maturity

1992 ◽  
Vol 122 (11) ◽  
pp. 2167-2173 ◽  
Author(s):  
Christiane Obled ◽  
Maurice Arnal
Keyword(s):  
Protein Synthesis ◽  
Whole Body ◽  
Body Protein

Measurement of protein turnover in the small intestine of lambs. 2. Effects of feed intake

1997 ◽  
Vol 128 (2) ◽  
pp. 233-246 ◽  
Author(s):  
S. A. NEUTZE ◽  
J. M. GOODEN ◽  
V. H. ODDY
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Small Intestine ◽  
Experimental Model ◽  
Feed Intake ◽  
Protein Turnover ◽  
Jugular Vein ◽  
Specific Radioactivity ◽  
Whole Body ◽  
Body Protein

This study used an experimental model, described in a companion paper, to examine the effects of feed intake on protein turnover in the small intestine of lambs. Ten male castrate lambs (∼ 10 months old) were offered, via continuous feeders, either 400 (n = 5) or 1200 (n = 5) g/day lucerne chaff, and mean experimental liveweights were 28 and 33 kg respectively. All lambs were prepared with catheters in the cranial mesenteric vein (CMV), femoral artery (FA), jugular vein and abomasum, and a blood flow probe around the CMV. Cr-EDTA (0·139 mg Cr/ml, ∼ 0·2 ml/min) was infused abomasally for 24 h and L-[2,6-3H]phenylalanine (Phe) (420±9·35 μCi into the abomasum) and L-[U-14C]phenylalanine (49·6±3·59 μCi into the jugular vein) were also infused during the last 8 h. Blood from the CMV and FA was sampled during the isotope infusions. At the end of infusions, lambs were killed and tissue (n = 4) and digesta (n = 2) samples removed from the small intestine (SI) of each animal. Transfers of labelled and unlabelled Phe were measured between SI tissue, its lumen and blood, enabling both fractional and absolute rates of protein synthesis and gain to be estimated.Total SI mass increased significantly with feed intake (P < 0·05), although not on a liveweight basis. Fractional rates of protein gain in the SI tended to increase (P = 0·12) with feed intake; these rates were −16·2 (±13·7) and 23·3 (±15·2) % per day in lambs offered 400 and 1200 g/day respectively. Mean protein synthesis and fractional synthesis rates (FSR), calculated from the mean retention of 14C and 3H in SI tissue, were both positively affected by feed intake (0·01 < P < 0·05). The choice of free Phe pool for estimating precursor specific radioactivity (SRA) for protein synthesis had a major effect on FSR. Assuming that tissue free Phe SRA represented precursor SRA, mean FSR were 81 (±15) and 145 (±24) % per day in lambs offered 400 and 1200 g/day respectively. Corresponding estimates for free Phe SRA in the FA and CMV were 28 (±2·9) and 42 (±3·5) % per day on 400 g/day, and 61 (±2·9) and 94 (±6·0) on 1200 g/day. The correct value for protein synthesis was therefore in doubt, although indirect evidence suggested that blood SRA (either FA or CMV) may be closest to true precursor SRA. This evidence included (i) comparison with flooding dose estimates of FSR, (ii) comparison of 3H[ratio ]14C Phe SRA in free Phe pools with this ratio in SI protein, and (iii) the proportion of SI energy use associated with protein synthesis.Using the experimental model, the proportion of small intestinal protein synthesis exported was estimated as 0·13–0·27 (depending on the choice of precursor) and was unaffected by feed intake. The contribution of the small intestine to whole body protein synthesis tended to be higher in lambs offered 1200 g/day (0·21) than in those offered 400 g/day (0·13). The data obtained in this study suggested a role for the small intestine in modulating amino acid supply with changes in feed intake. At high intake (1200 g/day), the small intestine increases in mass and CMV uptake of amino acids is less than absorption from the lumen, while at low intake (400 g/day), this organ loses mass and CMV uptake of amino acids exceeds that absorbed. The implications of these findings are discussed.

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