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Keywords: amino acid
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Articles
Journal:
Clinical Science
Clin Sci (Lond) (2010) 119 (11): 465–466.
Published: 17 August 2010
... 7 2010 15 7 2010 15 7 2010 © The Authors Journal compilation © 2010 Biochemical Society 2010 amino acid cachexia heart failure inflammation insulin proteolysis sarcopenia The syndrome of CHF [chronic HF (heart failure)] is a complex multi-organ response mechanism to...
Abstract
Derangements in systemic and local metabolism develop in patients with CHF [chronic HF (heart failure)] and contribute to the progression of the disease. Impaired skeletal muscle metabolism, morphology and function leading to exercise intolerance are hallmarks of the syndrome of CHF. These changes result in abnormal glucose and lipid metabolism, and the associated insulin resistance, which contribute to progression of skeletal muscle catabolism and development of muscle atrophy in patients with advanced HF. In the present issue of Clinical Science , Toth and co-workers demonstrate the impairment of skeletal muscle protein metabolism in patients with HF, and specifically show an impaired anabolic response in the skeletal muscle of these patients following a period of nutritional deficiency.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (2010) 119 (11): 467–476.
Published: 17 August 2010
... (insulin and amino acids) and whether alterations in protein metabolism correlate to circulating cytokine levels. No differences in phenylalanine balance, rate of appearance or rate of disappearance were found between patients and controls under fasting conditions. However, the anabolic response to...
Abstract
Patients with chronic HF (heart failure) experience muscle atrophy during the course of the disease. The mechanisms underlying muscle atrophy in HF, however, are not understood. Thus we evaluated leg phenylalanine balance and kinetics in HF patients and controls following a brief fast (24 h) and under euglycaemic–hyperinsulinaemic–hyperaminoacidaemic conditions to determine whether HF increases muscle protein catabolism in response to nutritional deprivation and/or diminishes the anabolic response to meal-related stimuli (insulin and amino acids) and whether alterations in protein metabolism correlate to circulating cytokine levels. No differences in phenylalanine balance, rate of appearance or rate of disappearance were found between patients and controls under fasting conditions. However, the anabolic response to hyperinsulinaemia–hyperaminoacidaemia was reduced by more than 50% in patients compared with controls. The diminished anabolic response was due to reduced suppression of the leg phenylalanine appearance rate, an index of protein breakdown, in HF patients; whereas no group difference was found in the increase in the leg phenylalanine disappearance rate, an index of protein synthesis. The diminished responses of both phenylalanine balance and appearance rate to hyperinsulinaemia–hyperaminoacidaemia were related to greater circulating IL-6 (interleukin-6) levels. Our results suggest that, following a brief period of nutritional deprivation, HF patients demonstrate an impaired muscle protein anabolic response to meal-related stimuli, due to an inability to suppress muscle proteolysis, and that this diminished protein anabolic response correlates with markers of immune activation. The inability to stimulate muscle protein anabolism following periods of nutritional deficiency may contribute to muscle wasting in HF patients.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (2009) 117 (9): 339–344.
Published: 01 September 2009
... glutathione and amino acid metabolism. Previous studies in humans have demonstrated that ischaemia and reperfusion in skeletal muscle for up to 120 min have no major effect on muscle glutathione concentrations. Liver ischaemia and reperfusion in animals have demonstrated diverging results concerning...
Abstract
Glutathione is a major antioxidant, and, in the present study, we investigated whether a clinical model of short warm ischaemia and reperfusion of the human liver during surgery would influence glutathione and amino acid metabolism. Previous studies in humans have demonstrated that ischaemia and reperfusion in skeletal muscle for up to 120 min have no major effect on muscle glutathione concentrations. Liver ischaemia and reperfusion in animals have demonstrated diverging results concerning glutathione metabolism. In the present study, six patients with liver malignancies, undergoing liver resection during warm ischaemia, were included. Liver biopsies were obtained from healthy appearing liver tissue from both lobes before ischaemia and at maximal ischaemia, and from the remaining liver lobe after 5, 10, 15, 20, 25 and 30 min of reperfusion. The biopsies were analysed for glutathione, amino acids and lactate. Median ischaemia time was 28 (range, 15–36) min. Lactate increased 266% at maximal ischaemia ( P <0.05). No alterations in glutathione concentrations or the redox status of glutathione (GSH/total glutathione) were observed. Glutamate decreased 22% ( P <0.05) at maximal ischaemia and increased thereafter 72% at 30 min of reperfusion ( P <0.05). Alanine increased 105% at maximal ischaemia ( P <0.05) and was normalized during reperfusion. BCAAs (branched-chain amino acids) increased 67% at maximal ischaemia ( P <0.05). In conclusion, short-time ischaemia and reperfusion in the human liver did not affect glutathione concentrations, whereas changes were observed in amino acid concentrations during both ischaemia and reperfusion.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (2009) 117 (9): 321–330.
Published: 01 September 2009
... glucose- and amino-acid-responsive clonal insulin-secreting cell line BRIN-BD11. Aralar1 overexpression increased long-term (24 h) and acute (20 min) glucose- and amino-acid-stimulated insulin secretion, cellular glucose metabolism, L -alanine and L -glutamine consumption, cellular ATP and glutamate...
Abstract
In the present study, we have investigated the effects of the transduction with recombinant adenovirus AdCA-Aralar1 (aspartate–glutamate carrier 1) on the metabolism, function and secretory properties of the glucose- and amino-acid-responsive clonal insulin-secreting cell line BRIN-BD11. Aralar1 overexpression increased long-term (24 h) and acute (20 min) glucose- and amino-acid-stimulated insulin secretion, cellular glucose metabolism, L -alanine and L -glutamine consumption, cellular ATP and glutamate concentrations, and stimulated glutamate release. However, cellular triacylglycerol and glycogen contents were decreased as was lactate production. These findings indicate that increased malate–aspartate shuttle activity positively shifted β-cell metabolism, thereby increasing glycolysis capacity, stimulus–secretion coupling and, ultimately, enhancing insulin secretion. We conclude that Aralar1 is a key metabolic control site in insulin-secreting cells.
Articles
Neville H. McClenaghan, Siobhan M. Scullion, Brian Mion, Chandralal Hewage, J. Paul G. Malthouse, Peter R. Flatt, Philip Newsholme, Lorraine Brennan
Journal:
Clinical Science
Clin Sci (Lond) (2009) 116 (4): 341–351.
Published: 15 January 2009
...Neville H. McClenaghan; Siobhan M. Scullion; Brian Mion; Chandralal Hewage; J. Paul G. Malthouse; Peter R. Flatt; Philip Newsholme; Lorraine Brennan Acute insulin-releasing actions of amino acids have been studied in detail, but comparatively little is known about the β-cell effects of long-term...
Abstract
Acute insulin-releasing actions of amino acids have been studied in detail, but comparatively little is known about the β-cell effects of long-term exposure to amino acids. The present study examined the effects of prolonged exposure of β-cells to the metabolizable amino acid L -alanine. Basal insulin release or cellular insulin content were not significantly altered by alanine culture, but acute alanine-induced insulin secretion was suppressed by 74% ( P <0.001). Acute stimulation of insulin secretion with glucose, KCl or KIC (2-oxoisocaproic acid) following alanine culture was not affected. Acute alanine exposure evoked strong cellular depolarization after control culture, whereas AUC (area under the curve) analysis revealed significant ( P <0.01) suppression of this action after culture with alanine. Compared with control cells, prior exposure to alanine also markedly decreased ( P <0.01) the acute elevation of [Ca 2+ ] i (intracellular [Ca 2+ ]) induced by acute alanine exposure. These diminished stimulatory responses were partially restored after 18 h of culture in the absence of alanine, indicating reversible amino-acid-induced desensitization. 13 C NMR spectra revealed that alanine culture increased glutamate labelling at position C4 (by 60%; P <0.01), as a result of an increase in the singlet peak, indicating increased flux through pyruvate dehydrogenase. Consistent with this, protein expression of the pyruvate dehydrogenase kinases PDK2 and PDK4 was significantly reduced. This was accompanied by a decrease in cellular ATP ( P <0.05), consistent with diminished insulin-releasing actions of this amino acid. Collectively, these results illustrate the phenomenon of β-cell desensitization by amino acids, indicating that prolonged exposure to alanine can induce reversible alterations to metabolic flux, Ca 2+ handling and insulin secretion.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (2008) 114 (9): 603–610.
Published: 02 April 2008
... translation was quantified. Plasma glucose, and serum insulin, glycerol, triacylglycerols (triglycerides) and NEFAs (non-esterified fatty acids; ‘free fatty acids’) were not significantly altered during TPN infusion, whereas total plasma amino acids increased, as shown by increases in methionine...
Abstract
Previous studies have provided conflicting conclusions concerning the efficacy of improving protein balance in patients by standard intravenous nutrition [TPN (total parenteral nutrition)], which is either explained by suboptimal nutritional regimens or insensitive clinical methods. The aim of the present study was therefore to evaluate the effects on the initiation of translation of skeletal muscle proteins by standard overnight TPN. A total of 12 patients who underwent standard surgery were included. TPN was provided as an all-in-one treatment by constant infusion [0.16 gN·kg −1 of body weight·day −1 (30 kcal·kg −1 of body weight·day −1 )]. Saline-infused patients served as controls. Rectus abdominis muscle biopsies were taken at the time of the operation. The phosphorylation state of the proteins for initiation of translation was quantified. Plasma glucose, and serum insulin, glycerol, triacylglycerols (triglycerides) and NEFAs (non-esterified fatty acids; ‘free fatty acids’) were not significantly altered during TPN infusion, whereas total plasma amino acids increased, as shown by increases in methionine, phenylalanine, threonine, alanine, arginine, aspartic acid, glycine and histidine ( P <0.05). Overnight TPN increased the formation of active eIF4G–eIF4E (where eIF is eukaryotic-initiation factor) complexes ( P <0.05), whereas the inhibitory complex 4E-BP1 (eIF4E-binding protein)–eIF4E was moderately decreased ( P <0.06). TPN increased the amount of the most phosphorylated form of 4E-BP1 ( P <0.05), and increased the amount ( P <0.04) and phosphorylation ( P <0.01) of p70 S6K (70 kDa ribosomal protein S6 kinase). In conclusion, an overnight pre-operative constant infusion of standard TPN altered initiation factor complexes, indicating activation of the initiation of protein translation in rectus abdominis muscle in the presence of increased plasma amino acid levels, but without a concomitant increase in energy substrates and insulin. In contrast with our results from previous studies, the methodology used in the present study appears to be more sensitive in reflecting directional changes in human muscle protein synthesis compared with traditional methods, particularly based on measurements of amino acid flux.
Includes: Supplementary data
Articles
Marcel C. G. van de Poll, Sebastiaan J. P. Hanssen, Maaike Berbée, Nicolaas E. P. Deutz, Diethard Monbaliu, Wim A. Buurman, Cornelis H. C. Dejong
Journal:
Clinical Science
Clin Sci (Lond) (2008) 114 (3): 231–241.
Published: 08 January 2008
... C. G. van de Poll (email mcg.vandepoll@ah.unimaas.nl ). 24 4 2007 23 7 2007 21 8 2007 21 8 2007 © The Authors Journal compilation © 2008 Biochemical Society 2008 amino acid arginase-1 arginine cell injury liver resection hepatocyte transplantation The...
Abstract
Arginine is an important substrate in health and disease. It is a commonly held view that arginase-1 release from injured erythrocytes and hepatocytes leads to arginine breakdown; however, the true relationship between plasma arginase-1 concentration and activity has remained unaddressed. In the present study, blood was sampled from patients undergoing liver resection, a known cause of hepatocyte injury and arginase-1 release, to determine arginase-1, arginine and ornithine plasma levels. Arginase activity was assessed in vitro by measuring changes in arginine and ornithine plasma levels during incubation of plasma and whole-blood samples at 37 °C. Arginase-1 plasma levels increased 8–10-fold during liver resection, whereas arginine and ornithine levels remained unchanged. In accordance with these in vivo findings, arginine and ornithine levels remained unchanged in plasma incubated at 37 °C irrespective of the arginase-1 concentration. In contrast, arginine plasma levels in whole blood decreased significantly during incubation, with ornithine increasing stoichiometrically. These changes were irrespective of arginase-1 plasma levels and were explained by arginase activity present in intact erythrocytes. Next, plasma samples with 1000-fold normal arginase-1 concentrations were obtained from patients undergoing cadaveric liver transplantation. A significant decrease in arginine plasma levels occurred in vivo and in vitro . In contrast with commonly held views, moderately increased arginase-1 plasma levels do not affect plasma arginine. Very high plasma arginase-1 levels are required to induce potential clinically relevant effects.
Articles
Bo Westman, Lars Weidenhielm, Olav Rooyackers, Katarina Fredriksson, Jan Wernerman, Folke Hammarqvist
Journal:
Clinical Science
Clin Sci (Lond) (2007) 113 (7): 313–318.
Published: 03 September 2007
...Bo Westman; Lars Weidenhielm; Olav Rooyackers; Katarina Fredriksson; Jan Wernerman; Folke Hammarqvist The temporal pattern of metabolic alterations in muscle tissue during total ischaemia and reperfusion are not well-characterized in humans with respect to glutathione, amino acids and energy-rich...
Abstract
The temporal pattern of metabolic alterations in muscle tissue during total ischaemia and reperfusion are not well-characterized in humans with respect to glutathione, amino acids and energy-rich compounds. In the present study, knee replacement surgery was used as a clinical model to elucidate this pattern of metabolic alterations. Patients ( n =15) undergoing elective knee replacement surgery employing tourniquet ischaemia were studied. Muscle biopsies were taken from the quadriceps femoris muscle on the operated side preoperatively, at maximal ischaemia and after 24 h of reperfusion. The biopsies were analysed for glutathione, amino acids and energy-rich compounds. In addition the patients were randomized to receive either glucose or a mannitol infusion in the 24 h following tourniquet ischaemia. During ischaemia, muscle lactate increased by 400% ( P <0.05) and phosphocreatine decreased by 70% ( P <0.05). During the subsequent 24 h of reperfusion, muscle-reduced glutathione and total glutathione decreased by 27% and 22% ( P <0.05) respectively. The muscle amino acid pattern changed during ischaemia with an increase in alanine by 65% ( P <0.001) and a decrease in glutamate by 29% ( P <0.001). During the reperfusion part of the study, no differences attributable to the infusion of mannitol or glucose were observed. During tourniquet ischaemia and subsequent reperfusion, changes in glutathione metabolism developed, indicating oxidative stress. Knee replacement surgery as a clinical model was useful during the ischaemia period, whereas the reperfusion period was dominated by the general changes seen postoperatively.
Includes: Supplementary data
Articles
Yvonne L. J. Vissers, Maarten F. von Meyenfeldt, Yvette C. Luiking, Cornelis H. C. Dejong, Wim A. Buurman, Nicolaas E. P. Deutz
Journal:
Clinical Science
Clin Sci (Lond) (2007) 112 (10): 527–532.
Published: 12 April 2007
... 2007 amino acid arginine cancer metabolism nitric oxide stable isotope surgery We have described recently [ 1 ] that patients with malignant tumours inducing various degrees of metabolic derangements have decreased plasma arginine concentrations, even without weight loss being...
Abstract
We have described recently that cancer patients have low plasma arginine concentrations, even without weight loss being present, suggesting that decreased arginine availability may be a specific feature of the presence of tumour. As arginine is important in post-operative repair, we hypothesized that abnormalities in arginine metabolism in cancer lead to an aberrant post-operative response in arginine and NO metabolism. To investigate this, we studied post-operative alterations in arginine and NO production and the acute-phase response in MCA (methylcholanthrene) sarcoma-bearing mice. Controls, mice with small MCA tumours (<15% of carcass weight) and large MCA tumours (>15% of carcass weight) were studied, either with or without undergoing laparotomy. The stable isotopes L -[guanidino- 15 N 2 - 2 H 2 ]arginine and L -[ureido- 15 N]citrulline were used to study whole-body arginine and NO production rates. SAP (serum amyloid P component) concentrations were measured to assess the acute-phase response. Significance was tested using Mann–Whitney U test. In healthy FVB mice, laparotomy significantly increased whole-body arginine production (from 42±3 to 54±3 nmol·10 g −1 of carcass weight·min −1 ), NO production (from 1.1±0.1 to 1.4±0.2 nmol·10 g −1 of carcass weight·min −1 ) and levels of SAP (from 4±1 to 115±23 ng/ml), whereas in all MCA tumour-bearing mice baseline values of arginine metabolism and SAP concentration were already elevated and the response to laparotomy was absent. In conclusion, MCA tumour-bearing mice had a disturbed post-operative metabolic response, as evidenced by attenuated post-operative arginine and NO production, concomitant with an attenuated acute-phase response. This indicates that altered arginine metabolism may be an important characteristic of the metabolic changes in cancer.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (2005) 109 (6): 523–530.
Published: 23 November 2005
... following exercise may be due, in part, to an increase in the transport of L -arginine in CHF patients. Correspondence: Professor David M. Kaye (email david.kaye@baker.edu.au ). 1 6 2005 4 8 2005 19 8 2005 23 8 2005 The Biochemical Society 2005 amino acid cationic...
Abstract
We have reported previously a decrease in the clearance of the NO (nitric oxide) precursor L -arginine in the forearm circulation of CHF (congestive heart failure) patients, suggesting a potential rate-limiting mechanism contributing to the common finding of endothelial dysfunction in CHF. Given data that show exercise training augments endothelial function in CHF, the aim of the present study was to investigate whether these improvements were due to an increase in L -arginine transport. Measures of L -arginine transport, endothelial function and exercise capacity were repeated before and after 8 weeks of ‘usual living’ or exercise training in 21 CHF patients [NYHA (New York Heart Association) class II/III]. Exercise capacity (6-min walk test) increased following exercise training (496±21 to 561±17 m; P =0.005), whereas the control group demonstrated no change [488±18 to 484±21 m; P =ns (not significant)]. Basal FBF (forearm blood flow) remained stable following exercise training (2.68±0.55 to 2.46±0.32 ml·min −1 ·100 ml −1 of tissue) and ‘usual living’ (2.16±0.37 to 2.91±0.55 min −1 ·100 ml −1 of tissue). FBF responses to ACh (acetylcholine) increased following exercise by 49.6±17.7% (area under curve; P =0.01) demonstrating augmented endothelial function. FBF responses to SNP (sodium nitroprusside) were also improved following exercise training (30.8±8.2%; P =0.02). There was no change in vascular function in the ‘usual living’ group. The clearance of L -arginine was significantly increased following involvement in the exercise programme (69.4±7.8 to 101.0±9.5 ml/min; P =0.04), whereas there was no change in the ‘usual living’ group (78.4±17.5 to 81.0±14.9 ml/min; P =ns). In conclusion, the augmentation in endothelial function observed following exercise may be due, in part, to an increase in the transport of L -arginine in CHF patients.
Articles
Evelina GEORGIADES, Wilhelmina M. H. BEHAN, Liam P. KILDUFF, Marios HADJICHARALAMBOUS, Eileen E. MACKIE, John WILSON, Susan A. WARD, Yannis P. PITSILADIS
Journal:
Clinical Science
Clin Sci (Lond) (2003) 105 (2): 213–218.
Published: 01 August 2003
... (CFS), a disorder characterized chiefly by persistent, often debilitating, fatigue. We wished to characterize circulating profiles of putative amino acid modulators of CNS 5-hydroxytryptamine (5-HT; serotoninergic) and dopaminergic function in CFS patients at rest, as well as during symptom-limited...
Abstract
Considerable evidence points towards a prominent role for central nervous system (CNS) mechanisms in the pathogenesis of chronic fatigue syndrome (CFS), a disorder characterized chiefly by persistent, often debilitating, fatigue. We wished to characterize circulating profiles of putative amino acid modulators of CNS 5-hydroxytryptamine (5-HT; serotoninergic) and dopaminergic function in CFS patients at rest, as well as during symptom-limited exercise and subsequent recovery. Groups of 12 CFS patients and 11 age- and sex-matched sedentary controls, with similar physical activity histories, underwent ramp-incremental exercise to the limit of tolerance. Plasma amino acid concentrations, oxygen uptake and ratings of perceived exertion were measured at rest, and during exercise and recovery. Peak oxygen uptake was significantly lower in the CFS patients compared with controls. Rating of perceived exertion in the patients was higher at all time points measured, including at rest, relative to controls. Levels of free tryptophan (free Trp), the rate-limiting 5-HT precursor, were significantly higher in CFS patients at exhaustion and during recovery, whereas concentrations of branched-chain amino acids (BCAA) and large neutral amino acids (LNAA) were lower in CFS patients at exhaustion, and for LNAA also during recovery. Consequently, the [free Trp]/[BCAA] and [free Trp]/[LNAA] ratios were significantly higher in CFS patients, except at rest. On the other hand, levels of tyrosine, the rate-limiting dopaminergic precursor, were significantly lower at all time points in the CFS patients. The significant differences observed in a number of key putative CNS 5-HT and dopaminergic modulators, coupled with the exacerbated perception of effort, provide further evidence for a potentially significant role for CNS mechanisms in the pathogenesis of CFS.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (2002) 103 (6): 633–639.
Published: 19 November 2002
...Alan A. JACKSON; Rebecca L. DUNN; Michael C. MARCHAND; Simon C. LANGLEY-EVANS When rat dams consume a diet low in protein during pregnancy, their offspring develop high blood pressure. On a low-protein diet, the endogenous formation of the amino acid glycine is thought to become constrained...
Abstract
When rat dams consume a diet low in protein during pregnancy, their offspring develop high blood pressure. On a low-protein diet, the endogenous formation of the amino acid glycine is thought to become constrained. Glycine may become conditionally essential, as its rate of endogenous formation is inadequate to meet metabolic needs, and may be limiting for the normal development of the fetus. In the present study, five groups of Wistar rats were provided during pregnancy with one of five diets: a control diet containing 18% (w/w) casein (CON), a low-protein diet containing 9% casein (MLP), or the low-protein diet supplemented with 3% glycine (MLPG), alanine (MLPA) or urea (MLPU). The offspring were weaned on to standard laboratory chow, and blood pressure was measured at 4 weeks of age. Blood pressure was significantly increased in the MLP, MLPA and MLPU groups compared with the CON group, but for the MLPG group blood pressure was not significantly different from CON. Compared with the CON group, body weight was significantly reduced for the MLP, MLPA and MLPG groups, but for the MLPU group body weight was not different from CON. These data show that different forms of non-essential dietary nitrogen, when consumed during pregnancy, exert different effects upon the growth and function of the offspring. The availability of glycine appears to be of critical importance for normal cardiovascular development.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1999) 96 (6): 639–646.
Published: 11 May 1999
...Steven W. M. OLDE DAMINK; Ivo DE BLAAUW; Nicolaas E. P. DEUTZ; Peter B. SOETERS 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...
Abstract
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- 3 H]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.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1997) 92 (4): 423–430.
Published: 01 April 1997
... received three meals at 9.00 hours, 13.00 hours and 18.00 hours. Catecholamines and metabolites were determined by reverse-phase HPLC with electrochemical detection. Neutral amino acids were measured by ionexchange chromatography with photometric detection. 3. The food contained relatively little DOPA as...
Abstract
1. Plasma concentrations of 3,4-dihydroxyphenylalanine (DOPA), dopamine sulphate (DA-S), and 3,4-dihydroxyphenylacetic acid (DOPAC) in humans have been claimed to be indexes of sympathetic nervous activity, but the source and significance of plasma DOPA, DOPAC and DA-S have not been completely elucidated. 2. The effects of ordinary meals on plasma concentrations of total dopamine, mainly DA-S, DOPAC and DOPA were studied in seven healthy subjects. Venous blood was collected every hour for 25 h, while subjects were either fasting or received three meals at 9.00 hours, 13.00 hours and 18.00 hours. Catecholamines and metabolites were determined by reverse-phase HPLC with electrochemical detection. Neutral amino acids were measured by ionexchange chromatography with photometric detection. 3. The food contained relatively little DOPA as compared with phenylalanine, tyrosine, isoleucine and tryptophan. The content of DA and DA-S varied considerably, with the greatest amount in the evening meal of open sandwiches. 4. Plasma DOPA decreased significantly after the meals at 13.00 hours and 18.00 hours, whereas concentrations of the other amino acids increased as expected. 5. Plasma DA-S increased significantly after meals and especially after the evening meal. Increments in DA-S above basal values after a meal were closely related to the content of DOPA+DA+DA-S in the meal. Plasma DOPAC increased significantly after the evening meal. 6. The decrease in plasma DOPA observed after a meal was probably due to uptake of DOPA by muscle tissue. Changes in plasma DA-S and DOPAC during this 25-h study reflected to a large extent the content of DOPA, DA and DA-S in the meals.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1996) 90 (6): 457–466.
Published: 01 June 1996
... enhanced. Using valine and glutamine as tracers, the enhanced amino acid turnover rates were confirmed. 4. In conclusion, our results show that during short periods of starvation both methods give similar results. After prolonged starvation, however, an opposite change in disappearance rate and protein...
Abstract
1. Protein loss in muscle can be caused by decreased protein synthesis, increased breakdown or both. In small animals the tracer incorporation technique is mostly used to measure protein synthesis, but for degradation measurements in vitro or ex vivo settings are required. In human and large animal studies the arteriovenous dilution technique is used because it enables the measurement of synthesis and breakdown rates simultaneously. The applicability in small animals has not yet been proven. We used a starvation model to compare both techniques. 2. A primed constant infusion of l -[2,6- 3 H]phenylalanine was given to male Lewis rats after 16, 40, 64 and 112 h starvation. Protein synthesis rates of the gastrocnemius muscle were measured by the incorporation technique and compared with hindquarter protein turnover calculated in a two- and three-compartment arteriovenous dilution model. 3. Whole-body phenylalanine rate of appearance decreased from 456 ± 32 after 16 h to 334 ± 34 (nmol min −1 100 g −1 body weight) after 112 h starvation. Protein synthesis rates of the gastrocnemius muscle measured by the tracer incorporation technique decreased from 3.6 ± 0.4 after 16 h starvation to 2.2 ± 0.3 after 64 h starvation and 1.8 ± 0.4 (%/day) after 112h starvation. Hindquarter protein breakdown, calculated with the tracer dilution model, increased after 112 h starvation from 28 ± 12 to 77 ± 15 nmol min −1 100 g −1 body weight. Using the tracer dilution model, however, the calculated protein synthesis rate across the hindquarter also increased after prolonged starvation (29 ± 7 and 68 ± 16 nmol min −1 100 g −1 body weight after 16 and 112h respectively). In conjunction with this, calculated bidirectional membrane transport rates were also enhanced. Using valine and glutamine as tracers, the enhanced amino acid turnover rates were confirmed. 4. In conclusion, our results show that during short periods of starvation both methods give similar results. After prolonged starvation, however, an opposite change in disappearance rate and protein synthesis rate was observed. Assumptions made to calculate protein turnover using the arteriovenous dilution model may account for the discrepancy and care must be taken with the interpretation when using only one model in anaesthetized small animals.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1989) 76 (4): 419–422.
Published: 01 April 1989
... significant ( P = 0.02). A similar increase in V max. in uraemic cells compared with controls was seen in erythrocytes which were studied in zero-trans conditions after depletion of intracellular amino acids. The mean values of K m and K D were not significantly different in uraemia. The origins of this...
Abstract
1. The initial rate of l -lysine influx into erythrocytes from 13 patients with chronic renal failure has been measured using 14 C-labelled lysine. Ten patients were on maintenance haemodialysis and three had never been dialysed. The results are compared with data obtained from 12 normal individuals. 2. The rate of lysine influx into washed cells from buffered saline containing 0.02–0.5 mmol of l -lysine/l has been calculated. The results can be fitted with a model in which influx has a single saturable component obeying Michaelis–Menten kinetics, and a linear non-saturable component. 3. In uraemic erythrocytes the saturable component had a mean V max. of 0.762 mmol h −1 litre −1 of cells ( n = 13, sem 0.072) and a mean K m of 68.2 μmol/l ( sem 5.7). These values in normal erythrocytes were 0.566 mmol h −1 litre −1 of cells ( n = 12, sem 0.033) and 70.5 μmol/l ( sem 4.1), respectively. The mean apparent diffusion constant ( K D ) for the linear component of influx was 0.224 h −1 ( sem 0.039) in uraemic cells and 0.178 h −1 ( sem 0.028) in normals. 4. The 35% increase in mean V max. seen in uraemic erythrocytes was statistically significant ( P = 0.02). A similar increase in V max. in uraemic cells compared with controls was seen in erythrocytes which were studied in zero-trans conditions after depletion of intracellular amino acids. The mean values of K m and K D were not significantly different in uraemia. The origins of this increased membrane transport capacity for lysine in uraemia are discussed.
Articles
Journal:
Clinical Science
Clin Sci (Lond) (1985) 68 (3): 271–282.
Published: 01 March 1985
...Edward B. Fern; Peter J. Garlick; John C. Waterlow 1. The rate of protein synthesis in the whole body was measured in one fed subject with seven 15 N-labelled amino acids (intravenous and oral doses) and two 15 N protein mixtures (oral doses only). The rates were determined individually from the...
Abstract
1. The rate of protein synthesis in the whole body was measured in one fed subject with seven 15 N-labelled amino acids (intravenous and oral doses) and two 15 N protein mixtures (oral doses only). The rates were determined individually from the urinary excretion of ammonia and total urea over a 12 h experimental period. 2. Except with oral glycine and alanine, the synthesis rates given by ammonia and urea were appreciably different within each study when calculated on the assumption of a single pool of metabolic nitrogen in the body. In general, intravenous administration of the tracers gave higher rates with urea and the oral route gave higher rates with ammonia. 3. The differences between intravenous and oral doses of 15 N could be reduced significantly by calculating synthesis rates from either the arithmetic or harmonic average of flux rates given by ammonia and urea. The averages correspond to estimates of the total flux in a two-pool model of metabolic nitrogen when it is assumed either that both pools receive an equal amount of tracer (arithmetic) or that both have the same rate of nitrogen turnover (harmonic). 4. By so reducing the effect of physical separation of nitrogen in the body, the metabolic aspects of compartmentation of the tracer could be examined. The results show that the absolute value obtained for protein synthesis depends on the source of labelled nitrogen. The data are discussed in this empirical context.
Articles
Journal:
Clinical Science
Clin Sci Mol Med (1977) 52 (3): 311–318.
Published: 01 March 1977
... Science and Molecular Medicine (1977) 52, 3 11-3 18. Plasma glucose, non-esterified fatty acids and amino acids in Huntington s chorea 0. T. PHILLIPSON* AND E. I). B I R D MRC Neurochemical Pharmacology Unit, Department of Pharmacology, Medical School, University of Cambridge, Cambridge, (I. K. (Received...
Abstract
1. The metabolic responses to an oral glucose tolerance test (100 g) and an intravenous insulin provocation test (0·1 i.u./kg) were studied in nine control subjects and nine patients with Huntington's chorea. 2. Plasma glucose responses to these stimuli were identical in both groups. 3. High fasting concentrations of non-esterified fatty acid (NEFA) were recorded in the choreic patients when compared with control subjects. This difference was maintained under hypoglycaemic conditions. However, during hyperglycaemia the differences in NEFA concentrations between the groups was abolished. 4. Total plasma tryptophan concentrations were equal in the two groups. Free plasma tryptophan, however, was markedly reduced in the choreic group, and this appeared to be a result of a disturbed relationship between free tryptophan and NEFA concentrations. The abnormalities in free tryptophan values were sensitive to plasma glucose concentrations, as hyperglycaemic conditions markedly reduced the differences between the choreic and control group. 5. Patients with Huntington's chorea showed reduced fasting plasma concentrations of leucine, isoleucine and valine.
Articles
Journal:
Clinical Science
Clin Sci Mol Med (1976) 50 (6): 525–532.
Published: 01 June 1976
.... The use of a labelled essential amino acid would therefore give more accurate values for short-term measurements of whole body protein turnover. 14 7 1975 © 1976 The Biochemical Society and the Medical Research Society 1976 amino acid protein [ 14 C]tyrosine Clhical Science and...
Abstract
1. Six men were infused intravenously for 10 h with a tracer amount of l-[U- 14 C]tyrosine while on a standardized food intake. 2. Measurements of plasma l-[ 14 C]-tyrosine specific radioactivity and the excretion rate of 14 CO 2 were made at frequent intervals and showed plateau labelling of plasma and expired carbon dioxide within 6–8 h. The tyrosine flux was calculated from the specific radioactivity in plasma at plateau value. 3. The excretion rate of 14 CO 2 , corrected for retention of label within the bicarbonate pool, showed that oxidation accounted for 20% of the tyrosine flux. Urinary excretion of label was negligible. 4. Rates of protein synthesis were calculated from the flux of tyrosine after subtracting the proportion oxidized. Although the mean rate of synthesis was consistent with other measurements of protein turnover, the individual values ranged from 284 to 387 g/day. The variation was not reduced by relating turnover to body weight, lean body mass or energy expenditure. 5. Estimating the rates of protein breakdown from the tyrosine flux involved some assumptions about pathways of phenylalanine metabolism. The use of a labelled essential amino acid would therefore give more accurate values for short-term measurements of whole body protein turnover.
Articles
D. B. A. Silk, P. D. Fairclough, Nicola J. Park, Annette E. Lane, Joan P. W. Webb, M. L. Clark, A. M. Dawson
Journal:
Clinical Science
Clin Sci Mol Med (1975) 49 (5): 401–408.
Published: 01 November 1975
...D. B. A. Silk; P. D. Fairclough; Nicola J. Park; Annette E. Lane; Joan P. W. Webb; M. L. Clark; A. M. Dawson 1. A double-lumen perfusion technique was used to study the effect of a wide range of concentrations of the dipeptide glycyl-l-alanine and its constituent amino acids on water and...
Abstract
1. A double-lumen perfusion technique was used to study the effect of a wide range of concentrations of the dipeptide glycyl-l-alanine and its constituent amino acids on water and electrolyte absorption from iso-osmotic solutions in the upper jejunum of normal human subjects. 2. There was no significant absorption of water and electrolytes from sodium chloride solution (150 mmol/l) but the presence of the dipeptide or its constituent amino acids stimulated water and electrolyte absorption. 3. Water absorption reached a peak at increasing amino acid and dipeptide concentrations and then tailed off. Our data suggest that the tailing off is not solely due to the diminished sodium content of the solutions. 4. During perfusion of the dipeptide-sodium chloride and amino acid-sodium chloride solutions solute and water were absorbed as an iso-osmotic solution. Analysis of the results indicates that this could occur at high dipeptide concentrations only if the majority of the dipeptide enters the cell intact.