Effect of glutamine on leucine metabolism in humans

1996 ◽  
Vol 271 (4) ◽  
pp. E748-E754 ◽  
Author(s):  
R. G. Hankard ◽  
M. W. Haymond ◽  
D. Darmaun
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Specific Activity ◽  
Excretion Rate ◽  
The Other ◽  
Anabolic Effect ◽  
Protein Breakdown ◽  
Glutamine Concentration ◽  
Putative Protein

The aim of this study was to determine whether the putative protein anabolic effect of glutamine 1) is mediated by increased protein synthesis or decreased protein breakdown and 2) is specific to glutamine. Seven healthy adults were administered 5-h intravenous infusions of L-[1-14C]leucine in the postabsorptive state while receiving in a randomized order an enteral infusion of saline on one day or L-glutamine (800 mumol.kg-1.h-1, equivalent to 0.11 g N/kg) on the other day. Seven additional subjects were studied using the same protocol except they received isonitrogenous infusion of glycine. The rates of leucine appearance (RaLeu), an index of protein degradation, leucine oxidation (OxLeu), and nonoxidative leucine disposal (NOLD), an index of protein synthesis, were measured using the 14C specific activity of plasma alpha-ketoisocaproate and the excretion rate of 14CO2 in breath. During glutamine infusion, plasma glutamine concentration doubled (673 +/- 66 vs. 1,184 +/- 37 microM, P < 0.05), whereas RaLeu did not change (122 +/- 9 vs. 122 +/- 7 mumol. kg-1.h-1), OxLeu decreased (19 +/- 2 vs. 11 +/- 1 mumol.kg-1.h-1, P < 0.01), and NOLD increased (103 +/- 8 vs. 111 +/- 6 mumol. kg-1.h-1, P < 0.01). During glycine infusion, plasma glycine increased 14-fold (268 +/- 62 vs. 3,806 +/- 546 microM, P < 0.01), but, in contrast to glutamine, RaLeu (124 +/- 6 vs. 110 +/- 4 mumol. kg-1.h-1, P = 0.02), OxLeu (17 +/- 1 vs. 14 +/- 1 mumol.kg-1.h-1, P = 0.03), and NOLD (106 +/- 5 vs. 96 +/- 3 mumol.kg-1.h-1, P < 0.05) all decreased. We conclude that glutamine enteral infusion may exert its protein anabolic effect by increasing protein synthesis, whereas an isonitrogenous amount of glycine merely decreases protein turnover with only a small anabolic effect resulting from a greater decrease in proteolysis than protein synthesis.

Changes in protein turnover in rat uterus during pregnancy

1986 ◽  
Vol 250 (2) ◽  
pp. E114-E120 ◽  
Author(s):  
A. J. Morton ◽  
D. F. Goldspink
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Cathepsin D ◽  
Cell Loss ◽  
Protein Breakdown ◽  
Rat Uterus ◽  
Fractional Rate ◽  
Uterine Growth

The adaptive growth and protein turnover of the rat uterus were studied during the 21 days of gestation and up to 3 days after parturition. Despite large increases (13-fold) in uterine size during gestation, the fractional rate of protein synthesis (measured in vivo) remained unchanged when compared with nonpregnant tissue values of 44 +/- 5%/day. However, decreases were found in the rate of protein breakdown after implantation (i.e., 75% on day 7 and 28% on day 11) and in the activity of cathepsin D (i.e., 33 and 85% on days 8 and 16 of gestation). Changes in the degradative processes would therefore appear to be primarily responsible for the massive uterine growth during pregnancy. In contrast to the uterus the fractional rates of synthesis in the placenta and fetus progressively decreased during gestation. After parturition the uterus rapidly returned to its normal size by a combination of cellular atrophy and cell loss. After 2 days, a complementary decrease in the fractional rate of synthesis (30%) and an increase in protein degradation (2-fold) explained the process of involution.

scholarly journals Protein turnover in 3T3 cells transformed with the oncogene c-H-ras1

1992 ◽  
Vol 283 (2) ◽  
pp. 427-433 ◽  
Author(s):  
J M Gunn ◽  
G James
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Transformed Cells ◽  
Protein Breakdown ◽  
3T3 Cells ◽  
Short Term ◽  
Serum Stimulation ◽  
Increased Sensitivity ◽  
Dna And Protein Synthesis

We have examined protein turnover, growth, DNA synthesis and proliferation in three independent clones of 3T3-NR6 cells transformed with the oncogene c-H-ras1. We find that, firstly, the half-maximum concentration of serum and insulin regulating protein turnover in ras-transformed cells is significantly reduced from 0.5 to 0.3% for serum and from 4 nM to 0.5 nM for insulin, and, secondly, ras-transformed cells consistently have lower rates of protein degradation. The catabolic effect of conditioned medium or serum withdrawal is attenuated in transformed lines by maintaining lower basal rates of protein breakdown and higher basal rates of DNA and protein synthesis. Serum stimulation of growth in transformed cells is achieved in the short term by lower rates of protein breakdown rather than higher rates of protein synthesis: rates of protein synthesis become significantly higher 24 h after serum stimulation. Therefore transformed cells have higher rates of proliferation and grow to higher densities, but display characteristics common to normal cells because rates of protein synthesis decrease and protein degradation increase as a function of cell density. We conclude that higher basal rates of protein synthesis and growth with retention of the normal proliferative response to serum result from the pleiotropic nature of ras transformation, whereas lower rates of protein degradation and increased sensitivity to serum and insulin imply a direct regulatory role for ras.

Fiber-type composition of nine rat muscles. II. Relationship to protein turnover

1989 ◽  
Vol 257 (6) ◽  
pp. E828-E832 ◽  
Author(s):  
P. J. Garlick ◽  
C. A. Maltin ◽  
A. G. Baillie ◽  
M. I. Delday ◽  
D. A. Grubb
Keyword(s):  
Protein Synthesis ◽  
Regression Analysis ◽  
Protein Turnover ◽  
Fiber Type ◽  
Female Rats ◽  
Protein Breakdown ◽  
Fiber Type Composition ◽  
Type Composition ◽  
Age Regression

Rates of protein synthesis in vivo and fiber-type composition were measured in nine limb muscles of female rats at ages ranging from weaning to 1 yr. In all muscles, there was a decline in protein synthesis with increasing age, mostly as a result of a fall in the RNA content. Rates of protein breakdown and growth were determined in six muscles and these also declined with age. Regression analysis of the data for all ages showed that protein synthesis was correlated with the content of slow oxidative fibers but not with the relative proportions of fast glycolytic to fast oxidative glycolytic fibers.

Regulation of cardiac protein balance by hydrocortisone: interaction with insulin.

1978 ◽  
Vol 234 (3) ◽  
pp. E306
Author(s):  
E E Griffin ◽  
K Wildenthal
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Cathepsin D ◽  
Specific Activity ◽  
Branched Chain Amino Acids ◽  
Protein Balance ◽  
Net Uptake ◽  
Specific Activities ◽  
Branched Chain ◽  
Net Release

In fetal mouse hearts in organ culture the rate of protein synthesis was substantially reduced and the rate of protein degradation slightly increased by hydrocortisone in the absence of insulin, but in the presence of insulin the steroid caused a small increase in protein synthesis and a significant reduction in protein degradation. Hydrocortisone promoted the net uptake (or reduced the net release) of branched-chain amino acids independent of insulin and independent of simultaneous changes in protein balance. The specific activities of the lysosomal enzymes cathepsin D and glucosaminidase were reduced by hydrocortisone in all media, whereas the specific activity of creatine kinase increased when the medium contained insulin but decreased in the absence of insulin. It is concluded that hydrocortisone regulates cardiac protein balance via alterations both in synthesis and in degradation. Some of the hormone's myocardial effects are influenced by insulin so that hydrocortisone is anabolic in its presence but catabolic in its absence.

Effects of insulin-like growth factor-I, insulin, and leucine on protein turnover and ubiquitin ligase expression in rainbow trout primary myocytes

2010 ◽  
Vol 298 (2) ◽  
pp. R341-R350 ◽  
Author(s):  
Beth M. Cleveland ◽  
Gregory M. Weber
Keyword(s):  
Protein Synthesis ◽  
Rainbow Trout ◽  
Growth Factor ◽  
Protein Degradation ◽  
Ubiquitin Ligase ◽  
Protein Turnover ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The effects of insulin-like growth factor-I (IGF-I), insulin, and leucine on protein turnover and pathways that regulate proteolytic gene expression and protein polyubiquitination were investigated in primary cultures of 4-day-old rainbow trout myocytes. Supplementing media with 100 nM IGF-I increased protein synthesis by 13% ( P < 0.05) and decreased protein degradation by 14% ( P < 0.05). Treatment with 1 μM insulin increased protein synthesis by 13% ( P < 0.05) and decreased protein degradation by 17% ( P < 0.05). Supplementing media containing 0.6 mM leucine with an additional 2.5 mM leucine did not increase protein synthesis rates but reduced rates of protein degradation by 8% ( P < 0.05). IGF-I (1 nM–100 nM) and insulin (1 nM-1 μM) independently reduced the abundance of ubiquitin ligase mRNA in a dose-dependent manner, with maximal reductions of ∼70% for muscle atrophy F-box (Fbx) 32, 40% for Fbx25, and 25% for muscle RING finger-1 (MuRF1, P < 0.05). IGF-I and insulin stimulated phosphorylation of FOXO1 and FOXO4 ( P < 0.05), which was inhibited by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin, and decreased the abundance of polyubiquitinated proteins by 10–20% ( P < 0.05). Supplementing media with leucine reduced Fbx32 expression by 25% ( P < 0.05) but did not affect Fbx25 nor MuRF1 transcript abundance. Serum deprivation decreased rates of protein synthesis by 60% ( P < 0.05), increased protein degradation by 40% ( P < 0.05), and increased expression of all ubiquitin ligases. These data suggest that, similar to mammals, the inhibitory effects of IGF-I and insulin on proteolysis occur via P I3-kinase/protein kinase B signaling and are partially responsible for the ability of these compounds to promote protein accretion.

scholarly journals Effects of glucose and insulin on the activation of lipoprotin lipase and on protein-synthesis in rat adipose tissue

1980 ◽  
Vol 188 (1) ◽  
pp. 193-199 ◽  
Author(s):  
S M Parkin ◽  
K Walker ◽  
P Ashby ◽  
D S Robinson
Keyword(s):  
Protein Synthesis ◽  
Enzyme Activity ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Specific Activity ◽  
The Other ◽  
Lipoprotein Lipase Activity ◽  
Fat Bodies ◽  
Rat Adipose Tissue ◽  
Adipose Tissue Lipoprotein Lipase

Glucose, and certain sugars that can readily be converted to glucose 6-phosphate, bring about an activation of adipose-tissue lipoprotein lipase when epididymal fat-bodies from starved rats are incubated in the presence of cycloheximide. Other substrates do not support the activation. If the tissue is preincubated in the presence of cycloheximide for longer than 2h, the ability of added glucose to activate the enzyme is lost. On the other hand, the addition of glucose still brings about an increase in lipoprotein lipase activity after preincubation in the absence of cycloheximide for as long as 4h. The magnitude of the increase in enzyme activity brought about by the addition of glucose is increased when protein synthesis is stimulated during the preincubation period by insulin. The results are interpreted in terms of the existence in adipose tissue of a proenzyme pool of lipoprotein lipase that is normally maintained by protein synthesis and that is converted to complete enzyme of higher specific activity by a process that specifically requires glucose.

scholarly journals The effects of calcium on protein turnover in skeletal muscles of the rat

1982 ◽  
Vol 204 (1) ◽  
pp. 257-264 ◽  
Author(s):  
S E M Lewis ◽  
P Anderson ◽  
D F Goldspink
Keyword(s):  
Protein Synthesis ◽  
Cyclic Nucleotides ◽  
Protein Turnover ◽  
Skeletal Muscles ◽  
Extensor Digitorum Longus ◽  
Muscle Protein ◽  
Ionophore A23187 ◽  
Protein Breakdown ◽  
External Concentration ◽  
The Media

Several experimental procedures were used to increase the intracellular concentration of Ca2+ and determine its effects on protein turnover in isolated extensor digitorum longus and soleus muscle. These methods included the use of ionophore A23187, caffeine, dibucaine, thymol and procaine, all agents known to induce the release of calcium by acting either on the sarcolemma and/or on the sarcoplasmic reticulum. Another approach involved varying the external concentration of Ca2+ in the media in which the muscles were incubated. The changes in muscle Ca2+ concentrations after exposure to the various calcium-releasing agents were in keeping with accepted modes of action of these agents on muscle membranes. The findings suggest that increasing the sarcoplasmic concentration of Ca2+ inhibits protein synthesis and enhances protein breakdown. These catabolic effects of Ca2+ are compared with the changes induced in muscle protein turnover after exposure to insulin or cyclic nucleotides, and in myopathic muscle and situations of work overload. Attention is also drawn to some of the difficulties involved in definitively implicating Ca2+ as a factor involved in the normal regulation of protein turnover.

scholarly journals PROTEIN METABOLISM IN TUMOR CELLS AT VARIOUS STAGES OF GROWTH IN VIVO

1974 ◽  
Vol 62 (3) ◽  
pp. 585-593 ◽  
Author(s):  
Massimo Olivotto ◽  
Francesco Paoletti
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Tumor Cells ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Specific Activity ◽  
Cell Mass ◽  
Ascites Hepatoma ◽  
Two Phases

Protein metabolism of Yoshida ascites hepatoma cells was studied in the early phase of logarithmic proliferation and in the following stage in which cell mass remains constant (resting phase). The rate of protein synthesis was measured by a short-time incorporation of [8H]lysine, while degradation was concurrently assessed by following the decrease of specific activity of [14C]lysine-labeled proteins. Most of the labeled amino acid injected intraperitoneally into the animal was immediately available for the tumor cells, with only a minor loss towards the extra-ascitic compartment. It was thus possible to calculate the dilution of the isotope in the ascitic pool of the lysine, which increased concurrently with the ascitic plasma volume. Amino acid transport capacity did not change in the log vs. the resting cells. This fact permitted the correction of the specific activity of the proteins synthesized by tumors in the two phases, taking into account the dilution effect. Protein synthesis was found to proceed at a constant rate throughout each of the two phases, although it was 30% lower during the resting as compared to the log phase. When cell mass attained the steady-state, protein degradation occurred at such a level as to balance the synthesis. Throughout the resting phase the amount of lysine taken up by the cells and renewed from the blood remained unchanged. Protein turnover, as studied in subcellular fractions, exhibited a similar rate in nuclei and microsomes, where it proceeded at a higher level than in mitochondria. On the whole, the results encourage the use of the Yoshida ascites hepatoma as a suitable model for studying protein turnover in relation to cell growth in vivo.

scholarly journals Metabolic aspects of growth in HU-treated crown-gall tissue cultures. II. Helianthus annuus

2015 ◽  
Vol 46 (1) ◽  
pp. 101-118
Author(s):  
Aldona Rennert
Keyword(s):  
Protein Synthesis ◽  
Nucleic Acid ◽  
Crown Gall ◽  
Specific Activity ◽  
Tissue Growth ◽  
The Other ◽  
Tissue Cultures ◽  
Rna And Protein Synthesis ◽  
Crown Gall Tissue ◽  
Induced Changes

The dynamics of growth and changes in nucleic acid and protein contents in sunflower calluses and tumours cultured in hydroxyurea (HU) containing media were examined. HU-induced changes in healthy tissues ran in parallel always in the same direction, in tumourous ones however an uncoupling between DNA synthesis and tissue growth on one hand and RNA and protein synthesis on the other took place. A detailed analysis of the results allows to suppose that the specific activity of HU on tumourous tissue could be an index of: 1) quantitative disturbances in its genes function (2) degree of the lass of sensitivity to the factors of regulation.

scholarly journals Exercise-related changes in protein turnover in mammalian striated muscle

1991 ◽  
Vol 160 (1) ◽  
pp. 127-148 ◽  
Author(s):  
D. F. Goldspink
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Striated Muscle ◽  
Contractile Activity ◽  
Whole Body ◽  
Phenotypic Properties ◽  
Type Of Exercise ◽  
Passive Stretch

Contractile activity is an important determinant of the size, rate of protein turnover and phenotypic properties of muscle. Animal models that decrease muscle activity invariably accelerate the rate of protein degradation, usually complementing decreases in the rate of protein synthesis. The net effect is muscle atrophy. By contrast, increased activity and/or passive stretch enhance the synthesis of new proteins, whilst protein catabolism may be either decreased or increased. Muscle hypertrophy results. Endurance activities in man and animals usually induce cardiac hypertrophy, and increased fatigue resistance in skeletal muscle. During exercise the whole body and its skeletal musculature exhibit a negative nitrogen balance, and there is general agreement that rates of protein synthesis are decreased. Changes in protein degradation are, however, much less clearly defined. Resistance exercises induce the opposite changes, with the size of the heart remaining unchanged whilst the bulk and strength of skeletal muscle increase. No real consensus currently exists about the nature of the changes in protein turnover with this type of exercise. More carefully designed and executed experiments are required.

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