Renal handling of amino acids in 5/6-nephrectomized rats: Stimulation of renal amino acid reabsorption after treatment with triiodothyronine or dexamethasone under amino acid load

Glutamine may be a conditionally essential amino acid in low-birth-weight (LBW) preterm neonates. Exogenously administered amino acids, by providing anaplerotic carbon into the tricarboxylic acid cycle, could result in greater cataplerotic efflux and glutamine de novo synthesis. The effect of dose and duration of amino acid infusion on glutamine and nitrogen (N) kinetics was examined in LBW infants in the period immediately after birth. Preterm neonates (<32 weeks gestation, birth weights 809–1,755 g) were randomized to initially receive either 480 or 960 μmol·kg−1·h−1 of an intravenous amino acid solution for 19–24 hours, followed by a higher or lower amino acid load for either 5 h or 24 h. Glutamine de novo synthesis, leucine N, phenylalanine, and urea kinetics were determined using stable isotopic tracers. An increase in amino acid infusion from 480 to 960 μmol·kg−1·h−1 for 5 h resulted in decreased glutamine de novo synthesis in every neonate (384.4 ± 38.0 to 368.9 ± 38.2 μmol·kg−1·h−1, P < 0.01) and a lower whole body rate of proteolysis ( P < 0.001) and urea synthesis ( P < 0.001). However, when the increased amino acid infusion was extended for 24 h, glutamine de novo synthesis increased (369.7 ± 92.6 to 483.4 ± 97.5 μmol·kg−1·h−1, P < 0.001), whole body rate of proteolysis did not change, and urea production increased. Decreasing the amino acid load resulted in a decrease in glutamine rate of appearance (Ra) and leucine N Ra, but had no effect on phenylalanine Ra. Acutely stressed LBW infants responded to an increase in amino acid load by transiently suppressing whole body rate of glutamine synthesis, proteolysis, and oxidation of protein. The mechanisms of this transient effect on whole body protein/nitrogen metabolism remain unknown.

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Portal infusion of amino acids is more efficient than peripheral infusion in stimulating liver protein synthesis at the same hepatic amino acid load in dogs

American Journal of Clinical Nutrition ◽

10.1093/ajcn/88.4.986 ◽

2008 ◽

Vol 88 (4) ◽

pp. 986-996 ◽

Cited By ~ 9

Author(s):

Dominique Dardevet ◽

Scot R Kimball ◽

Leonard S Jefferson ◽

Alan D Cherrington ◽

Didier Rémond ◽

...

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Amino Acid ◽

Liver Protein ◽

Amino Acid Load ◽

Acid Load ◽

Portal Infusion

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The disposal of an intravenously administered amino acid load across the human forearm

Metabolism ◽

10.1016/0026-0495(82)90235-9 ◽

1982 ◽

Vol 31 (5) ◽

pp. 463-470 ◽

Cited By ~ 43

Author(s):

Naji N. Abumrad ◽

David Rabin ◽

Kendall L. Wise ◽

W.W. Lacy

Keyword(s):

Amino Acid ◽

Amino Acid Load ◽

Human Forearm ◽

Acid Load

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Differential effect of three commercial heparins on Na+/H+ exchange and growth of PASMC

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.270.2.l260 ◽

1996 ◽

Vol 270 (2) ◽

pp. L260-L265 ◽

Cited By ~ 7

Author(s):

C. G. Dahlberg ◽

B. T. Thompson ◽

P. M. Joseph ◽

H. G. Garg ◽

C. R. Spence ◽

...

Keyword(s):

Amino Acid ◽

Antiproliferative Activity ◽

Fluorescent Microscopy ◽

Variable Effect ◽

Chemical Content ◽

Acid Load ◽

Pulmonary Artery Smooth Muscle ◽

Intracellular Alkalinization ◽

Heparin Preparation ◽

Stimulation Of

Heparin preparations vary in chemical content and in antiproliferative activity for pulmonary artery smooth muscle cells (PASMC). Intracellular alkalinization via stimulation of the Na+/H+ antiporter appears to be a permissive event for proliferation of PASMC. We wondered whether the variable effect of heparin preparations on PASMC growth might be due to different degrees of inhibition of the Na+/H+ antiporter and whether variations in chemical formulation might correlate with the inhibition. Fluorescent microscopy of bovine PASMC was done using a dye with which fluorescence varies directly with intracellular pH (pHi). Bovine PASMC were preincubated with three heparin preparations previously shown to vary in antiproliferative activity, at 1.0 microgram/ml for 24 h. Platelet-derived growth factor (PDGF; 60 ng/ml) on PASMC without heparin resulted in a rise in pHi of 0.27 +/- 0.02 pH units. The rise in pH units in heparin-treated PASMC was 0.34 +/- 0.03 with Choay, 0.21 +/- 0.02 with Elkins-Sinn, and 0.07 +/- 0.02 with Upjohn (+/-SE; all P < 0.05; n = 5). Upjohn heparin incubation for as little as 15 min still impeded the rise in pH induced by PDGF. Heparin did not block the Na+/H+ exchanger directly, as it still restored pHi in response to an acid load. Compared with PASMC proliferation induced by 60 ng/ml PDGF, 1 microgram/ml of Choay, Elkins-Sinn, and Upjohn heparin produced -4 +/- 7.4, 1.4 +/- 4.8, and 48 +/- 2.2% inhibition of PDGF control, respectively (P < 0.05 for Upjohn compared with PDGF and Choay). The heparins varied in protein content and amino acid composition. However, amino acid and glucosamine composition, total sulfation, and extent of 3-O-sulfation did not predict their activity. Thus inhibition of PDGF activation of the Na+/H+ antiporter by a given heparin preparation correlated well with its ability to inhibit PASMC proliferation.

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Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans

Physiological Reviews ◽

10.1152/physrev.1992.72.2.419 ◽

1992 ◽

Vol 72 (2) ◽

pp. 419-448 ◽

Cited By ~ 205

Author(s):

R. L. Jungas ◽

M. L. Halperin ◽

J. T. Brosnan

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Urea Cycle ◽

Liver Mitochondria ◽

Carbon Flow ◽

Acid Oxidation ◽

Peripheral Tissues ◽

Amino Acid Oxidation ◽

Atp Production ◽

Acid Load

Significant gaps remain in our knowledge of the pathways of amino acid catabolism in humans. Further quantitative data describing amino acid metabolism in the kidney are especially needed as are further details concerning the pathways utilized for certain amino acids in liver. Sufficient data do exist to allow a broad picture of the overall process of amino acid oxidation to be developed along with approximate quantitative assessments of the role played by liver, muscle, kidney, and small intestine. Our analysis indicates that amino acids are the major fuel of liver, i.e., their oxidative conversion to glucose accounts for about one-half of the daily oxygen consumption of the liver, and no other fuel contributes nearly so importantly. The daily supply of amino acids provided in the diet cannot be totally oxidized to CO2 in the liver because such a process would provide far more ATP than the liver could utilize. Instead, most amino acids are oxidatively converted to glucose. This results in an overall ATP production during amino acid oxidation very nearly equal to the ATP required to convert amino acid carbon to glucose. Thus gluconeogenesis occurs without either a need for ATP from other fuels or an excessive ATP production that could limit the maximal rate of the process. The net effect of the oxidation of amino acids to glucose in the liver is to make nearly two-thirds of the total energy available from the oxidation of amino acids accessible to peripheral tissues, without necessitating that peripheral tissues synthesize the complex array of enzymes needed to support direct amino acid oxidation. As a balanced mixture of amino acids is oxidized in the liver, nearly all carbon from glucogenic amino acids flows into the mitochondrial aspartate pool and is actively transported out of the mitochondria via the aspartate-glutamate antiport linked to proton entry. In the cytoplasm the aspartate is converted to fumarate utilizing urea cycle enzymes; the fumarate flows via oxaloacetate to PEP and on to glucose. Thus carbon flow through the urea cycle is normally interlinked with gluconeogenic carbon flow because these metabolic pathways share a common step. Liver mitochondria experience a severe nonvolatile acid load during amino acid oxidation. It is suggested that this acid load is alleviated mainly by the respiratory chain proton pump in a form of uncoupled respiration.(ABSTRACT TRUNCATED AT 400 WORDS)

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Liver intracellular L-cysteine concentration is maintained after inhibition of the trans-sulfuration pathway by propargylglycine in rats

British Journal Of Nutrition ◽

10.1079/bjn19970198 ◽

1997 ◽

Vol 78 (5) ◽

pp. 823-831 ◽

Cited By ~ 22

Author(s):

Ana Triguero ◽

Teresa Barber ◽

Concha GarcÍa ◽

Inmaculada R. Puertes ◽

Juan Sastre ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Protein Degradation ◽

Histological Examination ◽

Blood Concentration ◽

Urea Cycle ◽

Blood Levels ◽

Liver And Kidney ◽

Amino Acid Homeostasis ◽

Stimulation Of

To study the fate of l-cysteine and amino acid homeostasis in liver after the inhibition of the trans-sulfuration pathway, rats were treated with propargylglycine (PPG). At 4 h after the administration of PPG, liver cystathionase (EC 4.4.1.1) activity was undetectable, l-cystathionine levels were significantly higher, l-cysteine was unchanged and GSH concentration was significantly lower than values found in livers from control rats injected intraperitoneally with 0.15 M-NaCl. The hepatic levels of amino acids that are intermediates of the urea cycle, l-ornithine, l-citrulline and l-arginine and blood urea were significantly greater. Urea excretion was also higher in PPG-treated rats when compared with control rats. These data suggest a stimulation of ureagenesis in PPG-treated rats. The inhibition of γ-cystathionase was reflected in the blood levels of amino acids, because the L-methionine: l-cyst(e)ine ratio was significantly higher in PPG-treated rats than in control rats; blood concentration of cystathionine was also greater. Histological examination of liver and kidney showed no changes in PPG-treated rats when compared with controls. The administration of N-acetylcysteine (NAC) to PPG-treated rats reversed the changes in blood urea and in liver GSH. These data suggest that when liver l-cysteine production was impaired by the blockage of the trans-sulfuration pathway, the concentration of this amino acid was maintained mainly by an increase in protein degradation and by a depletion in GSH concentration that may spare l-cysteine.

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Biochemical and behavioural effects of acute tryptophan depletion in abstinent bulimic subjects: a pilot study

Psychological Medicine ◽

10.1017/s003329170003748x ◽

1995 ◽

Vol 25 (5) ◽

pp. 995-1001 ◽

Cited By ~ 19

Author(s):

A. Oldman ◽

A. Walsh ◽

P. Salkovskis ◽

C. G. Fairburn ◽

P. J. Cowen

Keyword(s):

Amino Acid ◽

Food Intake ◽

Free Amino ◽

Acute Tryptophan Depletion ◽

Tryptophan Depletion ◽

Healthy Controls ◽

Behavioural Effects ◽

Amino Acid Load ◽

Healthy Female ◽

Acid Load

SYNOPSISWe studied the effect of acute tryptophan (TRP) depletion in a group of eight abstinent bulimic (BN) subjects and in 12 healthy female controls. Despite being free of episodes of bingeeating and vomiting for a prolonged period, the abstinent BN subjects still appeared to practice dietary restraint as judged by their food intake in a test meal. In addition, their plasma TRP concentrations were significantly lower than those of the controls. Administration of a TRP-free amino acid load (52 g) significantly lowered plasma total and free TRP. However, compared to a balanced amino acid load, this procedure did not have significant effects on mood, appetite or food intake in either the abstinent BN subjects or the healthy controls.

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Effects of flooding amino acids on incorporation of labeled amino acids into human muscle protein

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.275.1.e73 ◽

1998 ◽

Vol 275 (1) ◽

pp. E73-E78 ◽

Cited By ~ 42

Author(s):

Kenneth Smith ◽

Nigel Reynolds ◽

Shaun Downie ◽

Ayyub Patel ◽

Michael J. Rennie

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Amino Acid ◽

Large Dose ◽

Human Skeletal Muscle ◽

Muscle Protein ◽

Human Muscle ◽

Leucine Incorporation ◽

Nonessential Amino Acids ◽

Stimulation Of

We investigated the effects of the nature of the flooding amino acid on the rate of incorporation of tracer leucine into human skeletal muscle sampled by biopsy. Twenty-three healthy young men (24.5 ± 5.0 yr, 76.2 ± 8.3 kg) were studied in groups of four or five. First, the effects of flooding with phenylalanine, threonine, or arginine (all at 0.05 g/kg body wt) on the incorporation of tracer [13C]leucine were studied. Then the effects of flooding with labeled [13C]glycine [0.1 g/kg body wt, 20 atoms percent excess (APE)] and [13C]serine (0.05 g/kg body wt, 15 APE) on the incorporation of simultaneously infused [13C]leucine were investigated. When a large dose of phenylalanine or threonine was administered, incorporation of the tracer leucine was significantly increased (from 0.036 to 0.067 %/h and 0.037 to 0.070 %/h, respectively; each P < 0.01). However, when arginine, glycine, or serine was administered as a flooding dose, no stimulation of tracer leucine incorporation could be observed. These results, together with those previously obtained, suggest that large doses of individual essential, but not nonessential, amino acids are able to stimulate incorporation of constantly infused tracer amino acids into human muscle protein.

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Amino acid requirement for the growth-hormone stimulation of incorporation of precursors into protein and nucleic acids of liver slices

Biochemical Journal ◽

10.1042/bj1190629 ◽

1970 ◽

Vol 119 (4) ◽

pp. 629-634 ◽

Cited By ~ 40

Author(s):

M. J. Clemens ◽

A. Korner

Keyword(s):

Amino Acids ◽

Growth Hormone ◽

Protein Synthesis ◽

Amino Acid ◽

Mechanism Of Action ◽

Plasma Concentrations ◽

Liver Slices ◽

Hypophysectomized Rats ◽

Stimulation Of

1. Incorporation of [14C]leucine into protein in rat liver slices, incubated in vitro, increased as the concentration of unlabelled amino acids in the incubation medium was raised. A plateau of incorporation was reached when the amino acid concentration was 6 times that present in rat plasma. Labelling of RNA by [3H]orotic acid was not stimulated by increased amino acid concentration in the incubation medium. 2. When amino acids were absent from the medium, or present at the normal plasma concentrations, no effect of added growth hormone on labelling of protein or RNA by precursor was observed. 3. When amino acids were present in the medium at 6 times the normal plasma concentrations addition of growth hormone stimulated incorporation of the appropriate labelled precursor into protein of liver slices from normal rats by 31%, and into RNA by 22%. A significant effect was seen at a hormone concentration as low as 10ng/ml. 4. Under the same conditions addition of growth hormone also stimulated protein labelling in liver slices from hypophysectomized rats. Tissue from hypophysectomized rats previously treated with growth hormone did not respond to growth hormone in vitro. 5. No effect of the hormone on the rate or extent of uptake of radioactive precursors into acid-soluble pools was found. 6. Cycloheximide completely abolished the hormone-induced increment in labelling of both RNA and protein. 7. It was concluded that, in the presence of an abundant amino acid supply, growth hormone can stimulate the synthesis of protein in rat liver slices by a mechanism that is more sensitive to cycloheximide than is the basal protein synthesis. The stimulation of RNA labelling observed in the presence of growth hormone may be a secondary consequence of the hormonal effect on protein synthesis. 8. The mechanism of action of growth hormone on liver protein synthesis in vitro was concluded to be similar to its mechanism of action in vivo.

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THE CONTROL OF ARGININE-INDUCED INSULIN SECRETION IN THE RAT: THE ROLE OF CATECHOLAMINES

Journal of Endocrinology ◽

10.1677/joe.0.0580111 ◽

1973 ◽

Vol 58 (1) ◽

pp. 111-122 ◽

Cited By ~ 2

Author(s):

R. A. BACCHUS ◽

L. MEADE ◽

J. S. M. HUTCHINSON ◽

D. R. LONDON

Keyword(s):

Insulin Secretion ◽

Blood Glucose ◽

Amino Acid ◽

Insulin Response ◽

Catecholamine Metabolism ◽

Catecholamine Synthesis ◽

Amino Acid Load ◽

Acid Load ◽

Anaesthetized Rat

SUMMARY The effect of alterations in catecholamine metabolism on arginine-induced insulin release was studied in the anaesthetized rat. Alpha-methyl-p-tyrosine, which inhibits catecholamine synthesis, guanethidine, which prevents catecholamine release, and reserpine, which depletes catecholamine stores, all enhanced the secretion of insulin and reduced the rise in blood glucose after the amino acid load. Adrenalectomy, with or without corticosterone replacement, had a similar effect. Adrenaline inhibited the insulin response to arginine. It was concluded that in the rat, adrenergic mechanisms modulate the insulin response to arginine.

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