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Sample records for acute tryptophan depletion

  1. Recognizing emotions in faces : effects of acute tryptophan depletion and bright light

    aan het Rot, Marije; Coupland, Nicholas; Boivin, Diane B.; Benkelfat, Chawki; Young, Simon N.

    2010-01-01

    In healthy never-depressed individuals, acute tryptophan depletion (ATD) may selectively decrease the accurate recognition of fearful facial expressions. Here we investigated the perception of facial emotions after ATD in more detail. We also investigated whether bright light, which can reverse ATD'

  2. Converging evidence for central 5-HT effects in acute tryptophan depletion

    Crockett, Molly; Clark, Luke; Roiser, Jonathan; Robinson, Oliver; Cools, Roshan; Chase, Henry; Den Ouden, Hanneke; Apergis-Schoute, Annemieke; Campbell-Meiklejohn, Daniel; Seymour, Ben; Sahakian, Barbara; Rogers, Robert; Robbins, Trevor

    2012-01-01

    Acute tryptophan depletion (ATD), a dietary technique for manipulating brain serotonin (5-HT) function, has advanced our understanding of 5-HT mechanisms in the etiology and treatment of depression and other affective disorders.1 A recent review article in Molecular Psychiatry questioned the...

  3. The effect of acute tryptophan depletion on emotional distraction and subsequent memory

    Wang, Lihong; Mullette-Gillman, O’Dhaniel A.; Gadde, Kishore M; Kuhn, Cynthia M.; McCarthy, Gregory; Huettel, Scott A.

    2009-01-01

    Serotonin is a key neurotransmitter involved in emotional regulation and memory. A number of studies using acute tryptophan depletion (ATD) in healthy subjects have shown that a temporary serotonin reduction both induces a negative emotional bias and impairs long-term memory. However, little is known about the specific effects of ATD on emotional memory. Using functional magnetic resonance imaging (fMRI), we investigated the effect of ATD on negative memory and executive function in healthy v...

  4. Cognition following acute tryptophan depletion : Difference between first-degree relatives of bipolar disorder patients and matched healthy control volunteers

    Sobczak, S; Riedel, W J; Booij, I; Aan Het Rot, M; Deutz, N E P; Honig, A

    2002-01-01

    BACKGROUND: Serotonergic circuits have been proposed to mediate cognitive processes, particularly learning and memory. Cognitive impairment is often seen in bipolar disorders in relation to a possible lowered serotonergic turnover. METHODS: We investigated the effects of acute tryptophan depletion (

  5. Evaluation of acute tryptophan depletion and sham depletion with a gelatin-based collagen peptide protein mixture

    Stenbæk, D S; Einarsdottir, H S; Goregliad-Fjaellingsdal, T;

    2016-01-01

    Acute Tryptophan Depletion (ATD) is a dietary method used to modulate central 5-HT to study the effects of temporarily reduced 5-HT synthesis. The aim of this study is to evaluate a novel method of ATD using a gelatin-based collagen peptide (CP) mixture. We administered CP-Trp or CP+Trp mixtures ...... effects of CP-Trp compared to CP+Trp were observed. The transient increase in plasma Trp after CP+Trp may impair comparison to the CP-Trp and we therefore recommend in future studies to use a smaller dose of Trp supplement to the CP mixture....

  6. Effects of acute tryptophan depletion on executive function in healthy male volunteers

    Young Allan H

    2003-08-01

    Full Text Available Abstract Background Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT levels using the method of acute tryptophan depletion (ATD. Methods Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood. Results Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P P = 0.027, with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests. Conclusions The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions.

  7. Acute tryptophan depletion potentiates 3,4-methylenedioxymethamphetamine-induced cerebrovascular hyperperfusion in adult male Wistar rats.

    van Donkelaar, Eva L; Kelly, Paul A T; Dawson, Neil; Blokland, Arjan; Prickaerts, Jos; Steinbusch, Harry W M; Ferrington, Linda

    2010-05-15

    The serotonergic (5-hydroxytryptamine; 5-HT) dysfunction found in depression may affect not only brain function (mood) but also cerebrovascular control. Similar, but possibly occult, disturbances may also be induced by 3,4-methylenedioxymethamphetamine-induced neurotoxicity (MDMA, or "ecstasy"). Acute tryptophan depletion (ATD) is widely used to identify vulnerability to depression, and we hypothesized that repeated MDMA administration would increase the sensitivity of rats to this acute serotonergic challenge. In this study, male Wistar rats were injected with MDMA (20 mg kg(-1), twice daily for 4 days) and challenged 3 weeks later with ATD, induced by intragastric administration of a nutritional mixture with tryptophan (TRP) removed. Cerebral metabolism (CMRG) and blood flow (CBF) were measured in parallel groups of animals following ATD by using quantitative [(14)C]2-deoxyglucose and [(14)C]iodoantipyrine autoradiographic techniques, respectively. A significant reduction in paroxetine binding to 5-HT transporter sites in MDMA-treated rats indicated 5HT terminal depletion, whereas the plasma TRP/sum large neutral amino acids ratio was reduced by 40% following ATD. Under all experimental conditions, the normal close correlation between CBF and metabolic demand was maintained. However, a global analysis of all brain regions revealed a significant decrease in the overall ratio of CBF to CMRG after ATD in control animals, whereas a higher ratio was observed after ATD in the MDMA-treated group. This increase in blood flow relative to cerebral metabolism suggests an ATD-induced loss of cerebrovascular tone in MDMA-treated animals that could have pathophysiological consequences and might conceivably contribute to the behavioral dysfunction of depression. PMID:19998482

  8. Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests I. Review of Biochemical Aspects and Poor Specificity of Current Amino Acid Formulations

    Abdulla A.-B. Badawy

    2010-06-01

    Full Text Available The acute tryptophan or tyrosine plus phenylalanine depletion and loading tests are powerful tools for studying the roles of serotonin, dopamine and noradrenaline in normal subjects and those with behavioural disorders. The current amino acid formulations for these tests, however, are associated with undesirable decreases in ratios of tryptophan or tyrosine plus phenylalanine to competing amino acids resulting in loss of specificity. This could confound biochemical and behavioural findings. Compositions of current formulations are reviewed, the biochemical principles underpinning the tests are revisited and examples of unintended changes in the above ratios and their impact on monoamine function and behaviour will be demonstrated from data in the literature. The presence of excessive amounts of the 3 branched-chain amino acids Leu, Ile and Val is responsible for these unintended decreases and the consequent loss of specificity. Strategies for enhancing the specificity of the different formulations are proposed.

  9. Simplified dietary acute tryptophan depletion: effects of a novel amino acid mixture on the neurochemistry of C57BL/6J mice

    Cristina L. Sánchez

    2015-08-01

    Full Text Available Background: Diet and nutrition can impact on the biological processes underpinning neuropsychiatric disorders. Amino acid (AA mixtures lacking a specific neurotransmitter precursor can change the levels of brain serotonin (5-HT or dopamine (DA in the central nervous system. The availability of these substances within the brain is determined by the blood–brain barrier (BBB that restricts the access of peripheral AA into the brain. AA mixtures lacking tryptophan (TRP compete with endogenous TRP for uptake into the brain across the BBB, which in turn leads to a decrease in central nervous 5-HT synthesis. Objective: The present study compared the effects of a simplified acute tryptophan depletion (SATD mixture in mice on blood and brain serotonergic and dopaminergic metabolites to those of a commonly used acute tryptophan depletion mixture (ATD Moja-De and its TRP-balanced control (BAL. Design: The SATD formula is composed of only three large neutral AAs: phenylalanine (PHE, leucine (LEU, and isoleucine (ILE. BAL, ATD Moja-De, or SATD formulas were delivered to adult male C57BL/6J mice by gavage. TRP, monoamines, and their metabolites were quantified in blood and brain regions (hippocampus, frontal cortex, amygdala, caudate putamen, and nucleus accumbens. Results: Both ATD Moja-De and SATD significantly decreased levels of serum and brain TRP, as well as brain 5-HIAA and 5-HT compared with BAL. SATD reduced HVA levels in caudate but did not alter total DA levels or DOPAC. SATD decreased TRP and serotonergic metabolites comparably to ATD Moja-De administration. Conclusion: A simplified and more palatable combination of AAs can manipulate serotonergic function and might be useful to reveal underlying monoamine-related mechanisms contributing to different neuropsychiatric disorders.

  10. Serotonin 2A Receptors, Citalopram and Tryptophan-Depletion

    Macoveanu, Julian; Hornboll, Bettina; Elliott, Rebecca;

    2013-01-01

    neural correlates of inhibition using intravenous citalopram and acute tryptophan depletion during functional magnetic resonance imaging. We adapted the NoGo paradigm to isolate effects on inhibition per se as opposed to other aspects of the NoGo paradigm. Successful NoGo inhibition was associated with...... greater activation of the right IFG compared to control trials with alternative responses, indicating that the IFG is activated with inhibition in NoGo trials rather than other aspects of invoked cognitive control. Activation of the left IFG during NoGo trials was greater with citalopram than acute...

  11. Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests Part II: Normalisation of the Tryptophan and the Tyrosine Plus Phenylalanine to Competing Amino Acid Ratios in a New Control Formulation

    Abdulla A.-B. Badawy

    2010-06-01

    Full Text Available Current formulations for acute tryptophan (Trp or tyrosine (Tyr plus phenylalanine (Phe depletion and loading cause undesirable decreases in ratios of Trp or Tyr + Phe to competing amino acids (CAA, thus undermining the specificities of these tests. Branched-chain amino acids (BCAA cause these unintended decreases, and lowering their content in a new balanced control formulation in the present study led to normalization of all ratios. Four groups (n = 12 each of adults each received one of four 50 g control formulations, with 0% (traditional, 20%, 30%, or 40% less of the BCAA. The free and total [Trp]/[CAA] and [Phe + Tyr]/[BCAA + Trp] ratios all decreased significantly during the first 5 h following the traditional formulation, but were fully normalized by the formulation containing 40% less of the BCAA. We recommend the latter as a balanced control formulation and propose adjustments in the depletion and loading formulations to enhance their specificities for 5-HT and the catecholamines.

  12. The effects of acute tryptophan depletion on reactive aggression in adults with attention-deficit/hyperactivity disorder (ADHD and healthy controls.

    Marco Zimmermann

    Full Text Available BACKGROUND: The neurotransmitter serotonin (5-HT has been linked to the underlying neurobiology of aggressive behavior, particularly with evidence from studies in animals and humans. However, the underlying neurobiology of aggression remains unclear in the context of attention-deficit/hyperactivity disorder (ADHD, a disorder known to be associated with aggression and impulsivity. We investigated the effects of acute tryptophan depletion (ATD, and the resulting diminished central nervous serotonergic neurotransmission, on reactive aggression in healthy controls and adults with ADHD. METHODOLOGY/PRINCIPAL FINDINGS: Twenty male patients with ADHD and twenty healthy male controls were subjected to ATD with an amino acid (AA beverage that lacked tryptophan (TRP, the physiological precursor of 5-HT and a TRP-balanced AA beverage (BAL in a double-blind, within-subject crossover-study over two study days. We assessed reactive aggression 3.25 hours after ATD/BAL intake using a point-subtraction aggression game (PSAG in which participants played for points against a fictitious opponent. Point subtraction was taken as a measure for reactive aggression. Lowered rates of reactive aggression were found in the ADHD group under ATD after low provocation (LP, with controls showing the opposite effect. In patients with ADHD, trait-impulsivity was negatively correlated with the ATD effect on reactive aggression after LP. Statistical power was limited due to large standard deviations observed in the data on point subtraction, which may limit the use of this particular paradigm in adults with ADHD. CONCLUSIONS/SIGNIFICANCE: Together with previous findings, the data provide preliminary evidence of an inverse association between trait-impulsivity and the ATD effect on reactive aggression after LP (as assessed by the PSAG in patients with ADHD and that this relationship can be found in both adolescents and adults. Because of limited statistical power larger sample

  13. L-Tryptophan depletion bioreactor, a possible cancer therapy

    Rolf Bambauer

    2015-04-01

    Full Text Available The cancer therapeutic strategies knownto date are not adequate for all cancer patients. Most of them are followed by a high rate of side effects and complications. The L-tryptophan depletion bioreactor is described as a possible new method of cancer therapy. L-tryptophan is an essential amino acid which has been recognized as an important cancer nutrient and its removal can lead to destruction of the tumour. Normal human cells or tumor cells cannot synthesize L-tryptophan and therefore tumor resistance is unlikely to develop. L-tryptophan is also a constituent for different bio-molecules such as Serotonin, Melatonin, and is needed for other synthesis processes in the cell growth. L-tryptophan degrading enzymes with 3 iso-enzymes called tryptophan side chain oxydase (TSO I, II, III were isolated. The 3 iso-enzymes can be differentiated by tryptic digestion. They have different molecular weights with different effectivenesses. All the TSO enzymes have heme that can catalyze essentially similar reactions involving L-tryptophan as a substrate. The most effective TSO is the type TSO III. A column which contained TSO as a bioreactor was integrated in a plasmapheresis unit and tested it in different animals. In sheep and rabbits L-tryptophan depletion in plasma was shown at 95% and 100% rates respectively by a single pass through the bioreactor. The results in immune supprimized rats with tumors were impressive, too. In 20 different tumor cell lines there were different efficacies. Brest cancer and medulloblastoma showed the greatest efficacy of L-tryptophan degrading. The gene technology of TSO production from Pseudomonas is associated with formation of endotoxins. This disadvantage can be prevented by different washing procedures or by using fungal sources for the TSO production. TSO III is developed to treat cancer diseases successfully, and has low side effects. A combination of L-tryptophan depletion with all available cancer therapies is

  14. Tryptophan depletion in depressed patients occurs independent of kynurenine pathway activation.

    Hughes, Martina M; Carballedo, Angela; McLoughlin, Declan M; Amico, Francesco; Harkin, Andrew; Frodl, Thomas; Connor, Thomas J

    2012-08-01

    The kynurenine pathway (KP) and its rate-limiting tryptophan degrading enzyme indolamine 2,3-dioxygenase (IDO) have been implicated in the pathogenesis of depression. IDO expression is driven by inflammatory cytokines, and has been suggested as the link between inflammation and a serotonergic deficit in depression. Studies also indicate that inflammatory cytokines upregulate the serotonin transporter (SERT), representing another mechanism by which inflammation could influence serotonin availability. Here we examined circulating concentrations of inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-6), and the acute phase protein CRP alongside plasma tryptophan, kynurenine, kynurenic acid (KYNA) and 3-hydroxyanthranilic acid (3-HAA) concentrations, and whole blood mRNA expression of IDO, kynurenine aminotransferases (KAT I and II), kynurenine-3-monooxygenase (KMO), kynureninase and SERT in patients with major depressive disorder (MDD) compared with age and sex-matched controls. Whilst no changes in TNF-α or IL-1β were observed, plasma concentrations of IL-6, IFN-γ and CRP were increased in the depressed cohort. Despite this inflammatory phenotype, IDO expression or plasma kynurenine were not significantly different between MDD patients and controls. In addition, there was no difference between controls and depressives in concentrations of KYNA and 3-HAA, or in expression of enzymes KAT, KMO or kynureninase that drive their production. Nonetheless, a depletion in tryptophan was evident in depressed patients and was correlated with HAM-D scores. In addition, we failed to observe any difference in SERT mRNA expression in the blood cells from patients with MDD relative to controls. These data support the idea that a mild inflammatory signature is evident in MDD and is accompanied by reduced circulating tryptophan concentrations. However, we found no indication of KP activation in the depressed cohort suggesting that an alternative mechanism mediates the depletion of

  15. Tryptophan

    Tryptophan is an amino acid needed for normal growth in infants and for nitrogen balance in adults. ... The body uses tryptophan to help make niacin and serotonin. Serotonin is thought to produce healthy sleep and a stable mood. In order ...

  16. Effects of acute paroxetine administration on tryptophan metabolism and disposition in the rat.

    Badawy, A. A.; Morgan, C. J.

    1991-01-01

    1 The effects of acute oral administration of paroxetine on tryptophan metabolism and disposition were examined in the rat. 2 Basal liver tryptophan pyrrolase activity was inhibited by paroxetine in vitro and after oral administration. Maximum inhibition was caused by a 1 mg kg-1 dose. 3 Paroxetine administration also inhibited pyrrolase activity that had previously been enhanced by hormonal induction by cortisol or cofactor activation by haematin. The cortisol induction of the enzyme was, ho...

  17. The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*

    Adams Wilson, Jessica R.; Morandi, Alessandro; Girard, Timothy D.; Thompson, Jennifer L.; Boomershine, Chad S.; Shintani, Ayumi K.; Ely, E. Wesley; Pandharipande, Pratik P.

    2013-01-01

    Objectives Plasma tryptophan levels are associated with delirium in critically ill patients. Although tryptophan has been linked to the pathogenesis of other neurocognitive diseases through metabolism to neurotoxins via the kynurenine pathway, a role for kynurenine pathway activity in intensive care unit brain dysfunction (delirium and coma) remains unknown. This study examined the association between kynurenine pathway activity as determined by plasma kynurenine concentrations and kynurenine/tryptophan ratios and presence or absence of acute brain dysfunction (defined as delirium/coma-free days) in intensive care unit patients. Design, Setting, and Patients This was a prospective cohort study that utilized patient data and blood samples from the Maximizing Efficacy of Targeted Sedation and Reducing Neurologic Dysfunction trial, which compared sedation with dexmedetomidine vs. lorazepam in mechanically ventilated patients. Measurements and Main Results Baseline plasma kynurenine and tryptophan concentrations were measured using high-performance liquid chromatography with or without tandem mass spectrometry. Delirium was assessed daily using the Confusion Assessment Method for the Intensive Care Unit. Linear regression examined associations between kynurenine pathway activity and delirium/coma-free days after adjusting for sedative exposure, age, and severity of illness. Among 84 patients studied, median age was 60 yrs and Acute Physiology and Chronic Health Evaluation II score was 28.5. Elevated plasma kynurenine and kynurenine/tryptophan ratio were both independently associated with significantly fewer delirium/coma-free days (i.e., fewer days without acute brain dysfunction). Specifically, patients with plasma kynurenine or kynurenine/tryptophan ratios at the 75th percentile of our population had an average of 1.8 (95% confidence interval 0.6–3.1) and 2.1 (95% confidence interval 1.0–3.2) fewer delirium/coma-free days than those patients with values at the 25

  18. Sub-chronic dietary tryptophan depletion--an animal model of depression with improved face and good construct validity.

    Franklin, M; Bermudez, I; Murck, H; Singewald, N; Gaburro, S

    2012-02-01

    Sub-chronic tryptophan depletion (SCTD) is proposed as an animal model for depression. Aims were to test the hypothesis and optimise the time of SCTD-induced depression-related behaviour and associated biochemical changes. Sprague Dawley rats were treated with a low tryptophan (TRP) containing diet for 0, 7 or 14 days. Peripheral and central neurochemical markers were measured. SCTD-induced depression-related behaviour was assessed by the forced swim test (FST). Model sensitivity to antidepressants was tested by concomitant treatment with paroxetine. SCTD-induced significant reductions in weight gain and measures of peripheral and central TRP. Corticosterone, aldosterone and kynurenine (K), increased whilst kynurenic acid (KA), an NMDA antagonist decreased. 5-HT(2) receptor binding Bmax was enhanced but was reversed by paroxetine. Corticosterone and aldosterone were significantly negatively-correlated to weight gain. SCTD increased floating time and reduced swimming time in the FST but were reversed by paroxetine. Aldosterone was increased at 7 and 14 days, whereas other changes maximised at 14 days. Aldosterone may be an early marker or causal link for depression development. Increased corticosterone and brain tissue 5-HT-receptor density may be correlates of depressive behaviour. Consequential increases in NMDA signalling through increased K/KA ratios suggest the model may be useful for testing novel antidepressants. PMID:22074993

  19. Plasmakonzentrationen von Prolaktin, Cortisol, Thyreotropin, Trijodthyronin und Thyroxin bei Schlafentzug-Respondern unter Tryptophan-Depletion im Rahmen einer endogenen Depression

    Sasse, Jörg

    2000-01-01

    Zielbereiche der vorliegenden Arbeit stellten sowohl die Analysen zur Auswirkung eines Schlafentzuges (SE) unter Tryptophan-Depletion (TD) auf die hormonellen Parameter Prolaktin (PRL), Cortisol, Thyreotropin (TSH), Trijodthyronin (T3) und Thyroxin (T4) als auch die daraus resultierenden Rückschlüsse im Hinblick auf eine Verzahnung dieser Parameter nicht nur mit der depressiven Symptomatik sondern auch mit den SE-Wirkmechanismen dar. Zur Untersuchung dieser bislang im Rahmen der biologische...

  20. Acute hyponatremia after cardioplegia by histidine-tryptophane-ketoglutarate – a retrospective study

    Lindner Gregor

    2012-06-01

    Full Text Available Abstract Background Hyponatremia is the most common electrolyte disorder in hospitalized patients and is known to be associated with increased mortality. The administration of antegrade single-shot, up to two liters, histidine-tryptophane-ketoglutarate (HTK solution for adequate electromechanical cardiac arrest and myocardial preservation during minimally invasive aortic valve replacement (MIAVR is a standard procedure. We aimed to determine the impact of HTK infusion on electrolyte and acid–base balance. Methods In this retrospective analysis we reviewed data on patient characteristics, type of surgery, arterial blood gas analysis during surgery and intra-/postoperative laboratory results of patients receiving surgery for MIAVR at a large tertiary care university hospital. Results A total of 25 patients were included in the study. All patients were normonatremic at start of surgery. All patients developed hyponatremia after administration of HTK solution with a significant drop of serum sodium of 15 mmol/L (p  Conclusions Acute hyponatremia during cardioplegia with HTK solution is isotonic and should probably not be corrected without presence of hypotonicity as confirmed by measurement of serum osmolality.

  1. Studies on the application of tryptophan metabolites as indicators of acute radiation damage and their modification

    It has been the aim of the investigations to continue earlier studies on the amplication of tryptophan metabolites as biochemical indicators after irradiation. These metabolites are of interest as they apparently indicate radiation effects in contrast to other metabolites like taurine and deoxycytidine in a dose range which leads to acute radiation sickness with the consequence of death. This assumption has been confirmed by the results of these studies. Measurements in the urine of rats demonstrate that the excretion of kynurenic acid and of xanthurenic acid as well as especially the ratio of kynurenic acid/anthranilic acid increases considerably in those animals which die some days later. The excretion of the surviving anilic acid increases considerably in those animals which die some days later. The excretion of the surviving animals is characteristical different. This abnormal excretion is induced by changes of specific, hepatic enzyme activities. The investigations have shown that the effects on the enzyme activities apppear not only after X-rays irradiation but also after neutrons. The studies, which have been performed with human material on the NAD-metabolism, demonstrate that with respect to the enzyme activities in the spleen as well as to the urinary excretion the same or similar effects, which have been found with animal experiments, can be expected. (orig.) 891 MG/orig. 892 CKA

  2. Depletion of mucosal substance P in acute otitis media

    Cayé-Thomasen, Per; Schmidt, Peter Thelin; Hermansson, Ann; Holst, Jens Juul; Thomsen, Jens

    2004-01-01

    OBJECTIVE: The neuropeptide substance P (SP) is an inducer of neurogenic inflammation and bone resorption in the middle ear. Resorption of the bone tissue structures surrounding the middle ear cavity is a distinct feature of the initial stage of acute otitis media (AOM), which may be due to nerve...... fiber release of SP. MATERIAL AND METHODS: To investigate possible release of SP in the middle ear mucosa during AOM, we used a well-established rat model of AOM caused by Streptococcus pneumoniae. Following tissue extraction on Days 1, 3 and 6 post-inoculation, the mucosal concentration of SP was...... measured using a radioimmunoassay. RESULTS: Compared to sham-inoculated control ears, the concentration of SP was significantly reduced on Day 1 and even further reduced on Day 3, whereas partial replenishment was found on Day 6. CONCLUSION: SP seems to be depleted in the rat middle ear mucosa in the...

  3. The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa

    O'Hara, Caitlin Beth; Keyes, Alexandra; Renwick, Bethany Gwen; Leyton, Marco; Campbell, Iain Cameron; Schmidt, Ulrike Hermine

    2016-01-01

    This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressiv...

  4. Mechanism of decline in rat brain 5-hydroxytryptamine after induction of liver tryptophan pyrrolase by hydrocortisone: roles of tryptophan catabolism and kynurenine synthesis

    Young, Simon N.

    1981-01-01

    1 Two mechanisms have been proposed to explain the decline in brain tryptophan and 5-hydroxytryptamine (5-HT) after administration of hydrocortisone and the subsequent induction of liver pyrrolase. These are depletion of tryptophan by high rates of tryptophan catabolism and inhibition of tryptophan uptake by elevated levels of the tryptophan catabolite, kynurenine.

  5. Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia

    Henriksen, Louise T; Nersting, Jacob; Raja, Raheel A;

    2014-01-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy. The...

  6. The protective effect of L-tryptophan versus alpha lipoic acid against L-arginine-induced experimental acute pancreatitis in albino rats

    Lamia M. Farghaly* , Nagwan A. Sabak ** and Naglaa A. El-sherbeny

    2007-03-01

    Full Text Available Aim of the study: This study was conducted to investigate the possible protective effects of L- treptophan "a precursor of melatonin" and alpha lipoic acid against L- arginine-induced experimental acute pancreatitis in albino rats. Methods: Fourty adult male albino rats (200- 250g were randomized into 4 groups (n= 10. Group I, the control group was given 0.9% saline intraperitoneally (i.p. Group II, was given 500 mg/100g L-arginine (i.p as a single dose to induce acute pancreatitis. Group III: was given 250mg/kg L-tryptophan (i.p 30 min prior to L- arginine injection. Group IV: was given 50mg/kg alpha lipioc acid(i.p 30 min prior to L-arginine. Before scarifice, blood samples were obtained from all groups to assay serum amylase and interleukin 6. Animals were sacrificed after 6 hours. For the histopathological study, pancreatic tissue was prepared for histological (H&E, PAS histochemical ( Tween stain for lipases and immunohistochemical ( Bax stain for apoptosis techniques. Both qualitative and quantitative analyses were done to assess the degree of acinar cells affection Results: It was revealed that serum amylase and interleukin 6 in group II rose rapidly. Microscopically, severe acinar cells degeneration, interstitial edema, diffuse bleeding and inflammatory infiltration were demonstrated. These changes were markedly improved with the administration of both L- tryptophan and alpha lipoic acid. Conclusion: It was concluded that both L- tryptophan & alpha lipoic acid reduced the effects of L-arginine-induced acute pancreatitis with better protection achieved by L-tryptophan administration.

  7. Chlamydia exploit the mammalian tryptophan-depletion defense strategy as a counter-defensive cue to trigger a survival state of persistence

    Bonner, Carol A; Byrne, Gerald I.; Jensen, Roy A.

    2014-01-01

    We previously proposed that in Chlamydiaceae rapid vegetative growth and a quiescent state of survival (persistence) depend upon alternative protein translational profiles dictated by host tryptophan (Trp) availability. These alternative profiles correspond, respectively, with a set of chlamydial proteins having higher-than-predicted contents of Trp (“Up-Trp” selection), or with another set exhibiting lower-than-predicted contents of Trp (“Down-Trp” selection). A comparative evaluation of Chl...

  8. Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response

    Xing, Meichun; Wang, Xiaohui; Palmai-Pallag, Timea;

    2015-01-01

    The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We...... have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81 is...... required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity....

  9. INDOLEAMINE 2,3-DIOXYGENASE INDUCES EXPRESSION OF A NOVEL TRYPTOPHAN TRANSPORTER IN MOUSE AND HUMAN TUMOR CELLS1

    Silk, Jonathan D.; Lakhal, Samira; Laynes, Robert; Vallius, Laura; Karydis, Ioannis; Marcea, Cornelius; Boyd, C. A. Richard; Cerundolo, Vincenzo

    2011-01-01

    Indoleamine 2,3 dioxygenase (IDO) is the rate-limiting enzyme in the kynurenine pathway, catabolizing tryptophan to kynurenine. Tryptophan depletion by IDO expressing tumors is a common mechanism of immune evasion inducing regulatory T cells and inhibiting effector T cells. As mammalian cells cannot synthesize tryptophan, it remains unclear how IDO positive tumor cells overcome the detrimental effects of local tryptophan depletion.

  10. Tryptophan depletion and formation of alpha-aminoadipic and gamma-glutamic semialdehydes in porcine burger patties with added phenolic-rich fruit extracts.

    Ganhão, Rui; Morcuende, David; Estévez, Mario

    2010-03-24

    The effect of added fruit extracts on the oxidation of muscle proteins in porcine burger patties subjected to cooking and chill storage was studied. Extracts from arbutus berries (Arbutus unedo L., AU), common hawthorns (Crataegus monogyna L., CM), dog roses (Rosa canina L., RC), and elm-leaf blackberries (Rubus ulmifolius Schott, RU) were prepared, characterized, added to burger patties (3% of total weight), and evaluated as inhibitors of protein oxidation. Negative (no added extract, C) and positive control (added quercetin, 230 mg/kg, Q) groups were also included in the design. Protein oxidation was assessed by means of tryptophan loss using fluorescence spectroscopy (FS) and formation of the specific protein carbonyls alpha-aminoadipic (AAS) and gamma-glutamic semialdehyde (GGS) using liquid chromatography and mass spectroscopy (LC-MS). Both advanced methodologies (FS and LC-MS) were found to be reliable and specific protein oxidation measurements that allow us to gain chemical insight into protein oxidation. The mechanisms likely involved in the oxidative reactions affecting proteins during cooking and storage of burger patties are profusely discussed. Phenolic-rich fruit extracts protected tryptophan residues against oxidation and inhibited the formation of both semialdehydes in burger patties during cooking and subsequent chill storage. In general, RC, RU, and AU were the most effective inhibitors of protein oxidation, with this effect being more intense than that of pure polyphenols like quercetin. These fruit extracts could be considered functional ingredients as their antioxidant actions contribute to the enhancement of the nutritional value of the meat products. PMID:20170109

  11. The brain is a target organ after acute exposure to depleted uranium

    The health effects of depleted uranium (DU) are mainly caused by its chemical toxicity. Although the kidneys are the main target organs for uranium toxicity, uranium can also reach the brain. In this paper, the central effects of acute exposure to DU were studied in relation to health parameters and the sleep-wake cycle of adult rats. Animals were injected intraperitoneally with 144 ± 10 μg DU kg-1 as nitrate. Three days after injection, the amounts of uranium in the kidneys represented 2.6 μg of DU g-1 of tissue, considered as a sub-nephrotoxic dosage. The central effect of uranium could be seen through a decrease in food intake as early as the first day after exposure and shorter paradoxical sleep 3 days after acute DU exposure (-18% of controls). With a lower dosage of DU (70 ± 8 μg DU kg-1), no significant effect was observed on the sleep-wake cycle. The present study intends to illustrate the fact that the brain is a target organ, as are the kidneys, after acute exposure to a moderate dosage of DU. The mechanisms by which uranium causes these early neurophysiological perturbations shall be discussed

  12. Acute cholesterol depletion leads to net loss of the organic osmolyte taurine in Ehrlich Lettré tumor cells

    Villumsen, Kasper Rømer; Duelund, Lars; Lambert, Ian Henry

    2010-01-01

    reveals that cholesterol depletion increases TauT's affinity toward taurine but reduces its maximal transport capacity. Cholesterol depletion has no impact on TauT regulation by protein kinases A and C. Phospholipase A2 activity, which is required for the activation of volume-sensitive organic anion......In mammalian cells, the organic osmolyte taurine is accumulated by the Na-dependent taurine transporter TauT and released though the volume- and DIDS-sensitive organic anion channel. Incubating Ehrlich Lettré tumor cells with methyl-ß-cyclodextrin (5 mM, 1 h) reduces the total cholesterol pool to...... channel (VSOAC), is increased under isotonic and hypotonic conditions following cholesterol depletion, whereas taurine release under hypotonic conditions is reduced following cholesterol depletion. Hence, acute cholesterol depletion of Ehrlich Lettré cells leads to reduced TauT and VSOAC activities and at...

  13. Effects of maternal L-tryptophan depletion and corticosterone administration on neurobehavioral adjustments in mouse dams and their adolescent and adult daughters.

    Zoratto, Francesca; Berry, Alessandra; Anzidei, Francesca; Fiore, Marco; Alleva, Enrico; Laviola, Giovanni; Macrì, Simone

    2011-08-01

    Major depressive disorder (MDD), a pathology characterized by mood and neurovegetative disturbances, depends on a multi-factorial contribution of individual predisposition (e.g., diminished serotonergic transmission) and environmental factors (e.g., neonatal abuse or neglect). Despite its female-biased prevalence, MDD basic research has mainly focused on male rodents. Most of present models of depression are also devalued due to the fact that they typically address only one of the aforementioned pathogenetic factors. In this paper we first describe the basic principles behind mouse model development and evaluation and then articulate that current models of depression are intrinsically devalued due to poor construct and/or external validity. We then report a first attempt to overcome this limitation through the design of a mouse model in which the genetic and the environmental components of early risk factors for depression are mimicked together. Environmental stress is mimicked through the supplementation of corticosterone in the maternal drinking water while biological predisposition is mimicked through maternal access to an L-tryptophan (the serotonin precursor) deficient diet during the first week of lactation. CD1 dams and their offspring exposed to the L-tryptophan deficient diet (T) and to corticosterone (80mg/l; C) were compared to animal facility reared (AFR) subjects. T and C mice served as intermediate reference groups. Adolescent TC offspring, compared to AFR mice, showed decreased time spent floating in the forced-swim test and increased time spent in the open sectors of an elevated 0-maze. Adult TC offspring showed reduced preference for novelty, decreased breakpoints in the progressive ratio operant procedure and major alterations in central BDNF levels and altered HPA regulation. The route of administration and the possibility to control the independent variables predisposing to depressive-like symptoms disclose novel avenues towards the development

  14. The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa.

    O'Hara, Caitlin B; Keyes, Alexandra; Renwick, Bethany; Leyton, Marco; Campbell, Iain C; Schmidt, Ulrike

    2016-01-01

    This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR) exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN. PMID:26808920

  15. Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle.

    Peternelj, Tina Tinkara; Marsh, Susan A; Strobel, Natalie A; Matsumoto, Aya; Briskey, David; Dalbo, Vincent J; Tucker, Patrick S; Coombes, Jeff S

    2015-02-01

    Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. Although many skeletal muscle proteins are O-GlcNAcylated, the modification has not been extensively studied in this tissue, especially in the context of exercise. This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. DEM and exercise both reduced intracellular glutathione and increased O-GlcNAc. DEM upregulated OGT protein expression. The effects of the interventions were significant 4 h after exercise (P exercise. PMID:25416863

  16. The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa.

    Caitlin B O'Hara

    Full Text Available This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN, specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17 and healthy controls (HC, n = 15 were recruited. The acute phenylalanine/tyrosine depletion (APTD method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN.

  17. The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa

    O’Hara, Caitlin B.; Keyes, Alexandra; Renwick, Bethany; Leyton, Marco; Campbell, Iain C.; Schmidt, Ulrike

    2016-01-01

    This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR) exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN. PMID:26808920

  18. Chlamydia exploit the mammalian tryptophan-depletion defense strategy as a counter-defensive cue to trigger a survival state of persistence.

    Bonner, Carol A; Byrne, Gerald I; Jensen, Roy A

    2014-01-01

    We previously proposed that in Chlamydiaceae rapid vegetative growth and a quiescent state of survival (persistence) depend upon alternative protein translational profiles dictated by host tryptophan (Trp) availability. These alternative profiles correspond, respectively, with a set of chlamydial proteins having higher-than-predicted contents of Trp ("Up-Trp" selection), or with another set exhibiting lower-than-predicted contents of Trp ("Down-Trp" selection). A comparative evaluation of Chlamydiaceae proteomes for Trp content has now been extended to a number of other taxon families within the Chlamydiales Order. At the Order level, elevated Trp content occurs for transporters of nucleotides, S-adenosylmethionine (SAM), dicarboxylate substrates, and Trp itself. For Trp and nucleotide transporters, this is even more pronounced in other chlamydiae families (Parachlamydiaceae, Waddliaceae, and Simkaniaceae) due to extensive paralog expansion. This suggests that intracellular Trp availability served as an ancient survival cue for enhancement or restraint of chlamydial metabolism in the common Chlamydiales ancestor. The Chlamydiaceae Family further strengthened Up-Trp selection for proteins that function in cell division, lipopolysaccharide biosynthesis, and methyltransferase reactions. Some proteins that exhibit Up-Trp selection are uniquely present in the Chlamydiaceae, e.g., cytotoxin and the paralog families of polymorphic membrane proteins (Pmp's). A striking instance of Down-Trp selection in the Chlamydiaceae is the chorismate biosynthesis pathway and the connecting menaquinone pathway. The newly recognized 1,4-dihydroxy-6-napthoate pathway of menaquinone biosynthesis operates in Chlamydiaceae, whereas the classic 2-napthoate pathway is used in the other Chlamydiales families. Because of the extreme Down-Trp selection, it would appear that menaquinone biosynthesis is particularly important to the integrity of the persistent state maintained under conditions of

  19. Study on decorporating and detoxicating acute depleted uranium poison with some flavonoids

    In order to investigate decorporating and detoxicating acute depleted uranium poison of flavonoids, the decorporation effect of flavonoids with catechol group, chelating agent of catechols amino carboxylic acid type (8102) and dimethyl sulfoxide (DMSO) were studied under DU exposure and Wistar rats as animal model. In 3d later after injecting DU with dose of 20 mg/kg and then injecting flavonoids with dose of 10 mg/kg in abdomen, the mortality, uranium contents, kidney function and pathological observation of kidney were investigated. It has been found that nearly 20% mortality occurs both in the T2 and in T1 groups meanwhile 30% mortality occurs in the control group. But death has not been observed in 8102 group. The concentration of excreted urine uranium increases and the level of serum uranium decreases when T2 used. The retention of uranium in kidney with T2 group also increases. Large reducing of urea nitrogen and creatinine in serum has been observed in 8102 and F1 groups, and reducing of creatinine has also been observed in F2, T1 and T2 groups. The serious injury of kidney has not been observed in T2 group. The protection efficiency can be listed as T2> 8102>T1>F1>QU. It has been revealed that flavonoid T2 is the most effective protector from the damage and poison of DU. (authors)

  20. Acute dyskerin depletion triggers cellular senescence and renders osteosarcoma cells resistant to genotoxic stress-induced apoptosis

    Lin, Ping; Mobasher, Maral E.; Alawi, Faizan, E-mail: falawi@upenn.edu

    2014-04-18

    Highlights: • Dyskerin depletion triggers cellular senescence in U2OS osteosarcoma cells. • Dyskerin-depleted cells are resistant to apoptosis induced by genotoxic stress. • Chromatin relaxation sensitizes dyskerin-depleted cells to apoptosis. - Abstract: Dyskerin is a conserved, nucleolar RNA-binding protein implicated in an increasing array of fundamental cellular processes. Germline mutation in the dyskerin gene (DKC1) is the cause of X-linked dyskeratosis congenita (DC). Conversely, wild-type dyskerin is overexpressed in sporadic cancers, and high-levels may be associated with poor prognosis. It was previously reported that acute loss of dyskerin function via siRNA-mediated depletion slowed the proliferation of transformed cell lines. However, the mechanisms remained unclear. Using human U2OS osteosarcoma cells, we show that siRNA-mediated dyskerin depletion induced cellular senescence as evidenced by proliferative arrest, senescence-associated heterochromatinization and a senescence-associated molecular profile. Senescence can render cells resistant to apoptosis. Conversely, chromatin relaxation can reverse the repressive effects of senescence-associated heterochromatinization on apoptosis. To this end, genotoxic stress-induced apoptosis was suppressed in dyskerin-depleted cells. In contrast, agents that induce chromatin relaxation, including histone deacetylase inhibitors and the DNA intercalator chloroquine, sensitized dyskerin-depleted cells to apoptosis. Dyskerin is a core component of the telomerase complex and plays an important role in telomere homeostasis. Defective telomere maintenance resulting in premature senescence is thought to primarily underlie the pathogenesis of X-linked DC. Since U2OS cells are telomerase-negative, this leads us to conclude that loss of dyskerin function can also induce cellular senescence via mechanisms independent of telomere shortening.

  1. L -Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications

    Richard, Dawn M.; Dawes, Michael A.; Mathias, Charles W.; Ashley Acheson; Nathalie Hill-Kapturczak; Dougherty, Donald M.

    2009-01-01

    An essential component of the human diet, L-tryptophan is critical in a number of metabolic functions and has been widely used in numerous research and clinical trials. This review provides a brief overview of the role of L-tryptophan in protein synthesis and a number of other metabolic functions. With emphasis on L-tryptophan’s role in synthesis of brain serotonin, details are provided on the research uses of L-tryptophan, particularly L-tryptophan depletion, and on clinical trials that have...

  2. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    Jiang, Zhenzhou, E-mail: jiangcpu@yahoo.com.cn; Bao, Qingli, E-mail: bao_ql@126.com; Sun, Lixin, E-mail: slxcpu@126.com; Huang, Xin, E-mail: huangxinhx66@sohu.com; Wang, Tao, E-mail: wangtao1331@126.com; Zhang, Shuang, E-mail: cat921@sina.com; Li, Han, E-mail: hapo1101@163.com; Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn

    2013-01-15

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  3. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  4. L-tryptophan

    ... brain and serious side effects including heart problems, shivering and anxiety could occur. Do not take L- ... and cause serious side effects including heart problems, shivering, and anxiety. Do not take L-tryptophan if ...

  5. High doses of vitamin B6 in the rat are associated with inhibition of hepatic tryptophan metabolism and increased uptake of tryptophan into the brain

    Bender, D.A.; Totoe, L.

    1984-09-01

    Acute administration of vitamin B6 to rats (10 mg/kg body weight) led to reduced urinary excretion of N1-methyl nicotinamide and methyl pyridone carboxamide, indicating inhibition of the oxidative metabolism of tryptophan. There was a considerable reduction in the production of 14CO2 from (ring-2-14C)tryptophan, and a significant inhibition of hepatic tryptophan oxygenase when measured in liver homogenates, together with an increase in the concentration of tryptophan in plasma. There was an increase in both the concentration of tryptophan in the brain and the uptake into the brain of peripherally administered (3H)tryptophan, accompanied by a small increase in the rate of synthesis of 5-hydroxytryptamine in the brain. It is suggested that this increase in the uptake of tryptophan into the brain following a relatively large dose of vitamin B6 may explain the beneficial action of the vitamin in some cases of depressive illness.

  6. IL4I1 Is a Novel Regulator of M2 Macrophage Polarization That Can Inhibit T Cell Activation via L-Tryptophan and Arginine Depletion and IL-10 Production.

    Yinpu Yue

    Full Text Available Interleukin 4-induced gene-1 (IL4I1 was initially described as an early IL-4-inducible gene in B cells. IL4I1 protein can inhibit T cell proliferation by releasing its enzymatic catabolite, H2O2, and this effect is associated with transient down-regulation of T cell CD3 receptor-zeta (TCRζ expression. Herein, we show that IL4I1 contributes to the regulation of macrophage programming. We found that expression of IL4I1 increased during bone marrow-derived macrophage (BMDM differentiation, expression of IL4I1 is much higher in primary macrophages than monocytes, and IL4I1 expression in BMDMs could be induced by Th1 and Th2 cytokines in two different patterns. Gene expression analysis revealed that overexpression of IL4I1 drove the expression of M2 markers (Fizz1, Arg1, YM-1, MR and inhibited the expression of M1-associated cytokines. Conversely, knockdown of IL4I1 by siRNA resulted in opposite effects, and also attenuated STAT-3 and STAT-6 phosphorylation. Furthermore, IL4I1 produced by macrophages catalyzed L-tryptophan degradation, while levo-1-methyl-tryptophan (L-1-MT, but not dextro-1-methyl-tryptophan, partially rescued IL4I1-dependent inhibition of T cell activation. Other inhibitors, such as diphenylene iodonium (DPI, an anti-IL-10Rα blocking antibody, and a nitric oxide synthase inhibitor, NG-monomethyl-L-arginine, also had this effect. Overall, our findings indicate that IL4I1 promotes an enhanced M2 functional phenotype, which is most likely associated with the phosphorylation of STAT-6 and STAT-3. Moreover, DPI, L-1-MT, NG-monomethyl-L-arginine, and anti-IL-10Rα blocking antibody were all found to be effective IL4I1 inhibitors in vitro.

  7. Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.

    Craig P Motbey

    Full Text Available Mephedrone (4-methylmethcathinone, MMC is a popular recreational drug, yet its potential harms are yet to be fully established. The current study examined the impact of single or repeated MMC exposure on various neurochemical and behavioral measures in rats. In Experiment 1 male adolescent Wistar rats received single or repeated (once a day for 10 days injections of MMC (30 mg/kg or the comparator drug methamphetamine (METH, 2.5 mg/kg. Both MMC and METH caused robust hyperactivity in the 1 h following injection although this effect did not tend to sensitize with repeated treatment. Striatal dopamine (DA levels were increased 1 h following either METH or MMC while striatal and hippocampal serotonin (5-HT levels were decreased 1 h following MMC but not METH. MMC caused greater increases in 5-HT metabolism and greater reductions in DA metabolism in rats that had been previously exposed to MMC. Autoradiographic analysis showed no signs of neuroinflammation ([(125I]CLINDE ligand used as a marker for translocator protein (TSPO expression with repeated exposure to either MMC or METH. In Experiment 2, rats received repeated MMC (7.5, 15 or 30 mg/kg once a day for 10 days and were examined for residual behavioral effects following treatment. Repeated high (30 mg/kg dose MMC produced impaired novel object recognition 5 weeks after drug treatment. However, no residual changes in 5-HT or DA tissue levels were observed at 7 weeks post-treatment. Overall these results show that MMC causes acute but not lasting changes in DA and 5-HT tissue concentrations. MMC can also cause long-term memory impairment. Future studies of cognitive function in MMC users are clearly warranted.

  8. Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis.

    Wang, Guohao; Liu, Xudong; Gaertig, Marta A; Li, Shihua; Li, Xiao-Jiang

    2016-03-22

    The Huntington's disease (HD) protein, huntingtin (HTT), is essential for early development. Because suppressing the expression of mutantHTTis an important approach to treat the disease, we must first understand the normal function of Htt in adults versus younger animals. Using inducibleHttknockout mice, we found thatHttdepletion does not lead to adult neurodegeneration or animal death at >4 mo of age, which was also verified by selectively depletingHttin neurons. On the other hand, young Htt KO mice die at 2 mo of age of acute pancreatitis due to the degeneration of pancreatic acinar cells. Importantly, Htt interacts with the trypsin inhibitor, serine protease inhibitor Kazal-type 3 (Spink3), to inhibit activation of digestive enzymes in acinar cells in young mice, and transgenicHTTcan rescue the early death of Htt KO mice. These findings point out age- and cell type-dependent vital functions of Htt and the safety of knocking down neuronal Htt expression in adult brains as a treatment. PMID:26951659

  9. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications

    Richard, Dawn M.; Dawes, Michael A.; Mathias, Charles W.; Acheson, Ashley; Hill-Kapturczak, Nathalie; Dougherty, Donald M.

    2009-01-01

    An essential component of the human diet, L-tryptophan is critical in a number of metabolic functions and has been widely used in numerous research and clinical trials. This review provides a brief overview of the role of L-tryptophan in protein synthesis and a number of other metabolic functions. With emphasis on L-tryptophan’s role in synthesis of brain serotonin, details are provided on the research uses of L-tryptophan, particularly L-tryptophan depletion, and on clinical trials that have...

  10. The protective effect of L-tryptophan versus alpha lipoic acid against L-arginine-induced experimental acute pancreatitis in albino rats

    Lamia M. Farghaly* , Nagwan A. Sabak ** and Naglaa A. El-sherbeny

    2007-01-01

    Aim of the study: This study was conducted to investigate the possible protective effects of L- treptophan "a precursor of melatonin" and alpha lipoic acid against L- arginine-induced experimental acute pancreatitis in albino rats. Methods: Fourty adult male albino rats (200- 250g) were randomized into 4 groups (n= 10). Group I, the control group was given 0.9% saline intraperitoneally (i.p). Group II, was given 500 mg/100g L-arginine (i.p) as a single dose to induce acute pancreatitis. Group...

  11. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

    Trisha A. Jenkins

    2016-01-01

    Full Text Available The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis.

  12. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis.

    Jenkins, Trisha A; Nguyen, Jason C D; Polglaze, Kate E; Bertrand, Paul P

    2016-01-01

    The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis. PMID:26805875

  13. Rotational spectrum of tryptophan

    Sanz, M. Eugenia, E-mail: maria.sanz@kcl.ac.uk; Cabezas, Carlos, E-mail: ccabezas@qf.uva.es; Mata, Santiago, E-mail: santiago.mata@uva.es; Alonso, Josè L., E-mail: jlalonso@qf.uva.es [Grupo de Espectroscopia Molecular (GEM), Edificio Quifima, Laboratorios de Espectroscopia y Bioespectroscopia, Unidad Asociada CSIC, Parque Científico Uva, Universidad de Valladolid, 47011 Valladolid (Spain)

    2014-05-28

    The rotational spectrum of the natural amino acid tryptophan has been observed for the first time using a combination of laser ablation, molecular beams, and Fourier transform microwave spectroscopy. Independent analysis of the rotational spectra of individual conformers has conducted to a definitive identification of two different conformers of tryptophan, with one of the observed conformers never reported before. The analysis of the {sup 14}N nuclear quadrupole coupling constants is of particular significance since it allows discrimination between structures, thus providing structural information on the orientation of the amino group. Both observed conformers are stabilized by an O–H···N hydrogen bond in the side chain and a N–H···π interaction forming a chain that reinforce the strength of hydrogen bonds through cooperative effects.

  14. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    Madden, Jill A. [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Hoyer, Patricia B. [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Devine, Patrick J. [INRS—Institut Armand-Frappier Research Centre, University of Quebec, Laval, QC H7V 1B7 (Canada); Keating, Aileen F., E-mail: akeating@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States)

    2014-05-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT{sup Thr308} protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  15. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKTThr308 protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  16. Tryptophan Metabolism in Allergic Disorders.

    Gostner, Johanna M; Becker, Katrin; Kofler, Heinz; Strasser, Barbara; Fuchs, Dietmar

    2016-01-01

    Allergic diseases such as asthma and rhinitis, as well the early phase of atopic dermatitis, are characterized by a Th2-skewed immune environment. Th2-type cytokines are upregulated in allergic inflammation, whereas there is downregulation of the Th1-type immune response and related cytokines, such as interferon-x03B3; (IFN-x03B3;). The latter is a strong inducer of indoleamine 2,3-dioxygenase-1 (IDO-1), which degrades the essential amino acid tryptophan, as part of an antiproliferative strategy of immunocompetent cells to halt the growth of infected and malignant cells, and also of T cells - an immunoregulatory intervention to avoid overactivation of the immune system. Raised serum tryptophan concentrations have been reported in patients with pollen allergy compared to healthy blood donors. Moreover, higher baseline tryptophan concentrations have been associated with a poor response to specific immunotherapy. It has been shown that the increase in tryptophan concentrations in patients with pollen allergy only exists outside the pollen season, and not during the season. Interestingly, there is only a minor alteration of the kynurenine to tryptophan ratio (Kyn/Trp, an index of tryptophan breakdown). The reason for the higher tryptophan concentrations in patients with pollen allergy outside the season remains a matter of discussion. To this regard, the specific interaction of nitric oxide (NO∙) with the tryptophan-degrading enzyme IDO-1 could be important, because an enhanced formation of NO∙ has been reported in patients with asthma and allergic rhinitis. Importantly, NO∙ suppresses the activity of the heme enzyme IDO-1, which could explain the higher tryptophan levels. Thus, inhibitors of inducible NO∙ synthase should be reconsidered as candidates for antiallergic therapy out of season that may abrogate the arrest of IDO-1 by decreasing the production of NO∙. Considering its association with the pathophysiology of atopic disease, tryptophan metabolism may

  17. Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion

    Zheng, J; Bizzozero, O. A.

    2010-01-01

    This study investigated the effect of reactive carbonyl species (RCS)-trapping agents on the formation of protein carbonyls during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH-depletor diethyl maleate in the absence or presence of chemically different RCS scavengers (hydralazine, methoxylamine, aminoguanidine, pyridoxamine, carnosine, taurine and z-histidine hydrazide). Despite their strong reactivity towards the most common RCS, none of the ...

  18. Exogenous Tryptophan Promotes Cutaneous Wound Healing of Chronically Stressed Mice through Inhibition of TNF-α and IDO Activation

    Bandeira, Luana Graziella; Bortolot, Beatriz Salari; Cecatto, Matheus Jorand; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

    2015-01-01

    Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on e...

  19. TRYPTOPHAN PROMOTES CHARITABLE DONATING

    Laura eSteenbergen

    2014-12-01

    Full Text Available The link between serotonin (5-HT and one of the most important elements of prosocial behavior, charity, has remained largely uninvestigated. In the present study, we tested whether charitable donating can be promoted by administering the food supplement L-Tryptophan (TRP, the biochemical precursor of 5-HT. Participants were compared with respect to the amount of money they donated when given the opportunity to make a charitable donation. As expected, compared to a neutral placebo, TRP appears to increase the participants’ willingness to donate money to a charity. This result supports the idea that the food we eat may act as a cognitive enhancer modulating the way we think and perceive the world and others.

  20. Deuteration of tryptophan and perlolyrine

    Deuterated tryptophan was prepared by simple exchange reactions in DC1 or D2O solution. The yield and abundance of deuterated tryptophan obtained from using DC1 as the deuterium solute was 92% and 98.5% respectively, whereas that by using D2O was 95% and 96.2% respectively. Deuterated perlolyrine was synthesized starting from deuterated tryptophan via acid-catalyzed ring-closure, aromatization and hydrolysis, with a yield of 11.6% and abundance of about 95%. The labelled perlolyrine was suitable for studying drug metabolism

  1. Tryptophan auxotrophs of Rhizobium japonicum.

    Wells, S E; Kuykendall, L D

    1983-01-01

    Eleven tryptophan-requiring mutants of Rhizobium japonicum I-110 ARS were isolated after nitrous acid mutagenesis and fell into five groups based on characterization by supplementation with intermediates and enzyme assays.

  2. Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion.

    Zheng, J; Bizzozero, O A

    2010-03-01

    This study investigated the effect of reactive carbonyl species (RCS)-trapping agents on the formation of protein carbonyls during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH-depletor diethyl maleate in the absence or presence of chemically different RCS scavengers (hydralazine, methoxylamine, aminoguanidine, pyridoxamine, carnosine, taurine and z-histidine hydrazide). Despite their strong reactivity towards the most common RCS, none of the scavengers tested, with the exception of hydralazine, prevented protein carbonylation. These findings suggest that the majority of protein-associated carbonyl groups in this oxidative stress paradigm do not derive from stable lipid peroxidation products like malondialdehyde (MDA), acrolein and 4-hydroxynonenal (4-HNE). This conclusion was confirmed by the observation that the amount of MDA-, acrolein- and 4-HNE-protein adducts does not increase upon GSH depletion. Additional studies revealed that the efficacy of hydralazine at preventing carbonylation was due to its ability to reduce oxidative stress, most likely by inhibiting mitochondrial production of superoxide and/or by scavenging lipid free radicals. PMID:20001647

  3. Tryptophan Research in Panic Disorder

    Eduard Maron; Jakov Shlik; Nutt, David J

    2008-01-01

    A considerable body of evidence suggests the involvement of serotonin neurotransmission in the pathogenesis of panic disorder. Research on pathways and functions of tryptophan, an essential amino acid converted into serotonin, may advance our understanding of serotonergic actions in panic disorder and related phenomena. The investigative approaches in this field include manipulations of tryptophan availability as well as genetic association and functional brain imaging studies. In this review...

  4. Enhanced Surfactant Adsorption via Polymer Depletion Forces: A Simple Model for Reversing Surfactant Inhibition in Acute Respiratory Distress Syndrome

    Stenger, Patrick C.; Zasadzinski, Joseph A.

    2006-01-01

    Lung surfactant adsorption to an air-water interface is strongly inhibited by an energy barrier imposed by the competitive adsorption of albumin and other surface-active serum proteins that are present in the lung during acute respiratory distress syndrome. This reduction in surfactant adsorption results in an increased surface tension in the lung and an increase in the work of breathing. The reduction in surfactant adsorption is quantitatively described using a variation of the classical Smo...

  5. Developing novel therapeutic strategies for acute lung injury and infection-peripheral blood monocyte depletion and prophylactic antimicrobial therapy

    Dhaliwal, Kanwaldeep

    2013-01-01

    BACKGROUND Acute lung injury (ALI) and nosocomial pneumonia are major causes of morbidity and mortality. There are 200,000 cases per year of ALI in the US with a mortality of 40%. On the intensive care unit (ICU), ALI accounts for over 40% of all ventilated patients at any one time. Despite this huge burden on healthcare and the relatively high prevalence, no therapies currently exist in clinical practice that attenuate the condition. The pathophysiology and aetiology of ALI is...

  6. Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels.

    Grammatikos, Georgios; Dietz, Julia; Ferreiros, Nerea; Koch, Alexander; Dultz, Georg; Bon, Dimitra; Karakasiliotis, Ioannis; Lutz, Thomas; Knecht, Gaby; Gute, Peter; Herrmann, Eva; Zeuzem, Stefan; Mavromara, Penelope; Sarrazin, Christoph; Pfeilschifter, Josef

    2016-01-01

    Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations. PMID:27304952

  7. Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan.

    Green, A. R.; Aronson, J K; Curzon, G; Woods, H F

    1980-01-01

    1 The metabolism of three oral doses of L-tryptophan (50, 25 and 10 mg/kg) in healthy young males has been investigated. 2 There was a linear relationship between both peak and area under curve of the total plasma tryptophan concentrations whilst the relationship between these parameters and plasma free tryptophan was hyperbolic. 3 Before the tryptophan load about 85% of plasma tryptophan was bound to albumin. As plasma tryptophan concentrations increased there was a hyperbolic increase in fr...

  8. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury

    Looney, Mark R.; Nguyen, John X.; Hu, Yongmei; Van Ziffle, Jessica A.; Lowell, Clifford A.; Matthay, Michael A

    2009-01-01

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the US. Previously, we established an immune-mediated TRALI mouse model, wherein mice with cognate antigen were challenged with MHC class I mAb. In this study, when mice housed in a rodent, specific pathogen–free barrier room were challenged with MHC I mAb, there was significant protection from TRALI compared with nonbarrier mice. Priming mice with LPS restored lung injury with mAb challe...

  9. Tryptophan supplementation and the response to unfairness in healthy volunteers

    Hilal eCerit

    2015-07-01

    Full Text Available Experimental manipulation of serotonin (5-HT availability has been shown to modulate social behavior. For instance, serotonin depletion increased the rejection rates of unfair offers in the Ultimatum Game (UG, whereas a single dose of the serotonin reuptake inhibitor (citalopram decreased rejection rates. These effects were observed immediately after the manipulation. The aim of this study was to investigate the effect of prolonged Tryptophan (TRP supplementation on UG performance in healthy individuals. A randomized double-blind placebo-controlled design was used. Healthy volunteers (N=47 completed the UG before and after a 6-day intervention of TRP (2.8 g/day or placebo. Impulsivity was measured with a Go-Stop task. The overall analyses showed that TRP supplementation had no significant effect on UG scores, but the direction of the effect was opposite from expectations. Because repeated performance of the UG may lead to unwanted learning effects or strategical changes, additional analyses were conducted in which participants (N=7 who accepted all offers on the second measurement were excluded. These analyses revealed that the TRP-group rejected very unfair offers more often than the placebo group. The groups did not differ on impulsivity. Increasing serotonin through TRP supplements increased the rejection of very unfair offers. The direction of our findings is inconsistent with earlier studies that showed that increasing 5-HT availability results in less rejection of unfair offers. The current findings thus importantly suggest that effects of acute vs. prolonged enhancement of 5-HT availability may differ. Also, the outcomes show that the UG is a complex task and participants’ decisions may depend on context, e.g., prior experience with the task.

  10. T-cell depleted haploidentical three loci mismatched bone-marrow and peripheral blood stem cell transplantation in acute leukaemia patients

    Objectives: Allogeneic bone-marrow transplantation (BMT) is an established treatment for many haematological malignancies. Unfortunately, most patients lack an HLA geno typically identical sibling and require an alternative donor, such as an HLA-haploidentical mismatched related donor, an HLA phenotypically matched or partially mismatched unrelated donor or an HLA-similar cord blood stem cell donor. However, these types of BMT increase the risk of graft-versus-host disease (GvHD), graft failure, delayed immuno reconstitution and fatal infection that observed after a sibling matched donor. Many centers are exploring the possibility of using donors other than matched sibling. Our approach has been to employ T-cell depleted mismatched haploidentical familial donor BMT to solve the problem of GvHD, a highly immuno- and myelo-suppressive conditioning regimen to reduce the incidence of graft failure and relapse, a graft inoculum plus G-CSF donor mobilized peripheral blood stem cells (PBSC) to overcome the host-versus-graft barrier. Patients and methods: Thirty-six patients (25 male, 11 female; median age 22 years, range 2-51) were treated with an allogeneic T-depleted haploidentical three loci mismatched bone-marrow and G-CSF mobilized PBSC transplantation from a familiar donor (18 siblings, 17 parents and 1 cousin) between March 1993 and June 1995. All had high-risk or advanced stage acute myeloid (12) or acute lymphoid (24) leukaemia; 18 were in haematological complete remission (CR) and 18 in chemo resistant relapse. Patients were conditioned with 8 Gy single dose TBI administered on day -5 at an instantaneous dose-rate of 13.4-31.7 cGy/min/midplane and average of 6.7-12.12 cGy/min/midplane. Shields were used to reduce the lung dose to 7 Gy in the first 23 cases and to 6 Gy in the last 13. 10 mg/Kg thiotepa were administered on day -4, 5 mg/Kg rabbit ATG from day -4 to day -1, 60 or 50 mg/Kg/cyclophosphamide on days -3 and -2. Bone-marrow and PBSC were infused on day

  11. The Toxicity of Depleted Uranium

    Wayne Briner

    2010-01-01

    Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a c...

  12. Nutritional Aspect of Tryptophan Metabolism

    Tsutomu Fukuwatari; Katsumi Shibata

    2013-01-01

    Mammals, including humans, can synthesize the vitamin nicotinamide from tryptophan in the liver. The resultant nicotinamide is distributed to non-hepatic tissues. We have studied the effects of changes in tryptophan–nicotinamide metabolism on niacin nutritional status. The liver plays a critical role in nicotinamide supply. Animal studies showed that the tryptophan–nicotinamide pathway is affected by physiological conditions, the presence of disease, nutrients, hormones, and chemicals. Human ...

  13. Autoxidation of tryptophan in aqueous solutions

    LJUBICA R. JOSIMOVIC; IVANA A. JANKOVIC

    2001-01-01

    Autoxidation of tryptophan was investigated in aqueous solutions by the gamma radiolytic technique. The oxygen uptake and formation of peroxide materials was followed as a function of pH, dose rate and concentration of tryptophan. The results obtained indicate that TrpH(OH)OO. radicals react with tryptophan by adduct formation thus propagating autoxidation. The chain propagation length (CPL) for a 2·102 mol dm3 tryptophan solution at pH 9.5 and a dose rate 0.01 Gy s1 was estimated to be ~ 5.8...

  14. Insuficiência respiratória aguda como manifestação da síndrome de eosinofilia-mialgia associada à ingestão de L-triptofano Acute respiratory failure as a manifestation of eosinophilia-myalgia syndrome associated with L-tryptophan intake

    Tiago de Araujo Guerra Grangeia

    2007-12-01

    Full Text Available A síndrome da eosinofilia-mialgia foi descrita em 1989 em pacientes que apresentavam mialgia progressiva e incapacitante e eosinofilia sérica, nos líquidos e secreções. A maioria dos pacientes relatava uso prévio de L-triptofano. Sintomas respiratórios são relatados em até 80% dos casos, eventualmente como manifestação única. O tratamento inclui suspensão da droga e corticoterapia. Relatamos o caso de uma mulher de 61 anos com insuficiência respiratória aguda após uso de L-triptofano, hidroxitriptofano e outras drogas. A paciente apresentava eosinofilia no sangue, lavado broncoalveolar e derrame pleural. Após a suspensão da medicação e corticoterapia, houve melhora clínica e radiológica em poucos dias.Eosinophilia-myalgia syndrome was described in 1989 in patients who presented progressive and incapacitating myalgia and eosinophilia in blood, fluids and secretions. Most patients report previous L-tryptophan intake. Respiratory manifestations are found in up to 80% of the cases, occasionally as the only manifestation. Treatment includes drug discontinuation and administration of corticosteroids. Here, we describe the case of a 61-year-old female admitted with acute respiratory failure after using L-tryptophan, hydroxytryptophan and other drugs. The patient presented eosinophilia, together with elevated eosinophil counts in the bronchoalveolar lavage and pleural effusion. After discontinuation of the drugs previously used, corticosteroids were administered, resulting in clinical and radiological improvement within just a few days.

  15. Inhibition of tryptophan - pyrrolase activity and elevation of brain tryptophan concentration by fluoxetine in rats

    Objective: To investigate in-vitro as well as in-vivo effects of various doses of fluoxetine (SSRI) on tryptophan metabolism in rates. Results: In in-vitro (10 - 1000 mM) as well in-vivo (0.5 - 30 mg/kg body wt.) studies, fluoxetine showed a statistically significant inhibition of rat liver tryptophan pyrrolase (tryptophan-2,3-dioxygenase; EC 1.13.11.11) activity. Significant increases were noted at 10 and 30 mg/kg doses in brain, serum (total and free) and liver L-tryptophan concentrations. Similarly, serum non-esterified free fatty acids showed a significant increase at both doses. There was no effect on serum glucose and albumin concentrations. Conclusion: It is suggested that major mechanism of action of fluoxetine is that of elevating brain tryptophan concentration and hence 5-HT synthesis by increasing the availability of circulating tryptophan to the brain secondarily to inhibition of major tryptophan degrading enzyme, hepatic tryptophan pyrrolase. It is assumed that fluoxetine inhibits the binding of apoenzyme form of tryptophan pyrrolase with its cofactor haem. The results are discussed in relation to possible involvement of disturbed hepatic tryptophan metabolism in depressive illness. (author)

  16. The Toxicity of Depleted Uranium

    Wayne Briner

    2010-01-01

    Full Text Available Depleted uranium (DU is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed.

  17. Serotonin release varies with brain tryptophan levels

    Schaechter, Judith D.; Wurtman, Richard J.

    1990-01-01

    This study examines directly the effects on serotonin release of varying brain tryptophan levels within the physiologic range. It also addresses possible interactions between tryptophan availability and the frequency of membrane depolarization in controlling serotonin release. We demonstrate that reducing tryptophan levels in rat hypothalamic slices (by superfusing them with medium supplemented with 100 microM leucine) decreases tissue serotonin levels as well as both the spontaneous and the electrically-evoked serotonin release. Conversely, elevating tissue tryptophan levels (by superfusing slices with medium supplemented with 2 microM tryptophan) increases both the tissue serotonin levels and the serotonin release. Serotonin release was found to be affected independently by the tryptophan availability and the frequency of electrical field-stimulation (1-5 Hz), since increasing both variables produced nearly additive increases in release. These observations demonstrate for the first time that both precursor-dependent elevations and reductions in brain serotonin levels produce proportionate changes in serotonin release, and that the magnitude of the tryptophan effect is unrelated to neuronal firing frequency. The data support the hypothesis that serotonin release is proportionate to intracellular serotonin levels.

  18. Volume-independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat. Evidence for mediation by tubuloglomerular feedback.

    Galla, J. H.; Bonduris, D N; Sanders, P W; Luke, R. G.

    1984-01-01

    We have recently described reduced superficial nephron glomerular filtration rate (SNGFR) in chloride-depletion alkalosis (CDA) without volume depletion. To elucidate the mechanism of this phenomenon, we studied three degrees of increasing severity of CDA (groups CDA-1, 2, and 3) produced by one or two peritoneal dialyses against 0.15 M NaHCO3 and electrolyte infusions of different Cl and HCO3 content in Sprague-Dawley rats; control rats (CON) were dialyzed against and infused with Ringers-HC...

  19. Tryptophan protection of phage from ultraviolet irradiation

    Bacteriophage SP02c12 and its isolated DNA were irradiated at 254 nm in tryptophan solutions. At a concentration of 10 mM, the amino acid exerted a protective effect on intact virus. The magnitude of this effect depended upon the length of time elapsed between mixing and irradiation. No protection was observed for solutions irradiated immediately after mixing. Tryptophan did not have a significant effect on UV sensitivity of the isolated viral DNA. No covalent crosslinking of tryptophan to DNA was observed. (author)

  20. l-Tryptophan Production by Achromobacter liquidum

    Ujimaru, Toshihiko; Kakimoto, Toshio; Chibata, Ichiro

    1983-01-01

    Conditions for the production of tryptophanase from Achromobacter liquidum and for the conversion of l-serine and indole to l-tryptophan were studied. The enzyme could be produced in amounts as great as 0.750 U/ml (degradation) and 0.294 U/ml (synthesis) by shaking cultures at 30°C in a medium containing dextrin, yeast extract, l-tryptophan, and l-glutamic acid. l-Tryptophan was produced most efficiently by shaking the cells at 37°C in a reaction mixture containing 60 mg of l-serine per ml, 6...

  1. Stable isotope labeled L-tryptophan

    Stable isotope labeled L-tryptophan is an application of nucleus technology in amino acids. Progresses in stable isotope labeled L-tryptophan in recent years are reviewed.. In the respect of synthesis, in addition to the methods of organic synthesis and isotope exchange, the microbial technology which has the advantage of U-label and construct has been used widely. In the respect of applications, stable isotope labeled L-tryptophan as trace has been used widely in yields of medicine, biology and chemistry et al. Along with the development of protein engineering, molecular biology and peptide drugs, they will have a fine future. (authors)

  2. Structural Characterization of New Microcystins Containing Tryptophan and Oxidized Tryptophan Residues

    David P. Hamilton; Stephen Craig Cary; Frode Rise; Miles, Christopher O.; Jonathan Puddick; Susanna A. Wood; Michèle R. Prinsep; Wilkins, Alistair L.

    2013-01-01

    Microcystins are cyclic peptides produced by cyanobacteria, which can be harmful to humans and animals when ingested. Eight of the (more than) 90 microcystin variants presently characterized, contain the amino acid tryptophan. The well-researched oxidation products of tryptophan; kynurenine, oxindolylalanine, and N-formylkynurenine, have been previously identified in intact polypeptides but microcystin congeners containing oxidized tryptophan moieties have not been reported. Liquid chromatogr...

  3. Identity determinants of E. coli tryptophan tRNA.

    Himeno, H; T. Hasegawa; Asahara, H; Tamura, K.; Shimizu, M

    1991-01-01

    The first base pair of the acceptor stem A1-U72 and the discriminator base G73, as well as the anticodon nucleotides, characterize the tryptophan tRNA in E. coli. To determine the contribution of these nucleotides to the tryptophan acceptor activity, various transcripts of E. coli tryptophan tRNA mutants were constructed. Substitutions of the discriminator base G73, which is conserved within prokaryotic tryptophan tRNAs, impaired aminoacylation with tryptophan. Substitutions of other purine-p...

  4. Depleted uranium

    Full text: The Director General of the International Atomic Energy Agency (IAEA), Mohamed ElBaradei, issued today the following statement: The IAEA has been involved in United Nations efforts relating to the impact of the use of depleted uranium (DU) ammunition in Kosovo. It has supported the United Nations Environment Programme (UNEP) in the assessment which it is making, at the request of the Secretary-General, of that impact. In this connection, in November 2000, Agency experts participated in a UNEP-led fact-finding mission in Kosovo. DU is only slightly radioactive, being about 40% as radioactive as natural uranium. Chemically and physically, DU behaves in the same way as natural uranium. The chemical toxicity is normally the dominant factor for human health. However, it is necessary to carefully assess the impact of DU in the special circumstances in which it was used, e.g. to determine whether it was inhaled or ingested or whether fragments came into close contact with individuals. It is therefore essential, before an authoritative conclusion can be reached, that a detailed survey of the territory in which DU was used and of the people who came in contact with the depleted uranium in any form be carried out. In the meantime it would be prudent, as recommended by the leader of the November UNEP mission, to adopt precautionary measures. Depending on the results of the survey further measures may be necessary. The Agency, within its statutory responsibilities and on the basis of internationally accepted radiation safety standards, will continue to co-operate with other organizations, in particular WHO and UNEP, with a view to carrying out a comprehensive assessment. Co-operation by and additional information from NATO will be prerequisites. The experience gained from such an assessment could be useful for similar studies that may be carried out elsewhere in the Balkans or in the Gulf. (author)

  5. Regulation of tryptophan genes in Rhizobium leguminosarum.

    Holmgren, E; I. P. Crawford

    1982-01-01

    Twelve tryptophan auxotrophs of Rhizobium leguminosarum were characterized biochemically. They were grown in complex and minimal media with several carbon sources, in both limiting and excess tryptophan. Missing enzyme activities allowed assignment of all mutant to the trpE, trpD, trpB, or trpA gene, confirming earlier results with the same mutants (Johnston et al., Mol. Gen. Genet. 165:323-330, 1978). In regulatory experiments, only the first enzyme of the pathway, anthranilate synthase, res...

  6. Pre-Transplant Donor-Specific T-Cell Alloreactivity Is Strongly Associated with Early Acute Cellular Rejection in Kidney Transplant Recipients Not Receiving T-Cell Depleting Induction Therapy

    Crespo, Elena; Lucia, Marc; Cruzado, Josep M.; Luque, Sergio; Melilli, Edoardo; Manonelles, Anna; Lloberas, Nuria; Torras, Joan; Grinyó, Josep M.; Bestard, Oriol

    2015-01-01

    Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90), to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67). We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction therapy. PMID:25689405

  7. Tryptophan auxotrophs were obtained by random transposon insertions in the Methanococcus maripaludis tryptophan operon.

    Porat, Iris; Whitman, William B

    2009-08-01

    Methanococcus maripaludis is an anaerobic, methane-producing archaeon that utilizes H(2) or formate for the reduction of CO(2) to methane. Tryptophan auxotrophs were constructed by in vitro insertions of the Tn5 transposon into the tryptophan operon, followed by transformation into M. maripaludis. This method could serve for rapid insertions into large cloned DNA regions. PMID:19566682

  8. Tryptophan auxotrophs were obtained by random transposon insertions in the Methanonococcus maripaludis tryptophan operon

    Porat, Iris; Whitman, William B.

    2009-01-01

    Methanococcus maripaludis is an anaerobic, methane-producing archaeon that utilizes H2 or formate for the reduction of CO2 to methane. Tryptophan auxotrophs were constructed by in vitro insertions of the Tn5 transposon into the tryptophan operon, followed by transformation into M. maripaludis. This method could serve for rapid insertions into large cloned DNA regions.

  9. Model reactions concerning the effects of gamma rays on tryptophan and peptides containing tryptophan

    The stability of heterocyclic reactive amino acid tryptophan (TRP) against the effects of gamma rays was examined in an aqueous medium. When doses in the range between 5 and 56 kGray were tested, the disintegration of tryptophan was seen toshow linear increases that were consistent with the intensity of irradiation. The radiolysis products obtained were condensed by means of high pressure liquid chromatography and subsequently determined using a method, in which gas chromatogr aphy was combined with mass spectroscope techniques. Irradiation was found to be the melanins of indole. The effects of the primary structure of peptides on the radiosensitivity of tryptophan are still open to discussion, as is the role of the neighbourhood groups in dipeptides and tripeptides that contain tryptophan. A systematic analysis of radiolysis products of tryptophan may provide valuable information on the development of mutagenic and carcinogenic radiolysis products during the irradiation of food products. (JH)

  10. Radiation induced decomposition of tryptophan in the presence of oxygen

    Tryptophan decomposition in oxygenated aqueous solutions in neutral media was investigated by gamma and pulsed electron irradiation. By using pulse radiolysis it was found that 27% of tryptophan OH-adducts eliminate water. Tryptophan neutral radical, Trp, thus formed reacts rapidly with O2-.. The remaining tryptophan OH-adducts react with oxygen to give peroxy radicals which may eliminate O2-., produce N-formylkynurenine and disproportionate yielding organic peroxides. Peroxy radicals derived from tryptophan H-adducts regenerate tryptophan by the elimination of HO2., and recombine with TrpH(OH)OO. radicals producing organic peroxides. (author)

  11. Tryptophan-Restriction Diets Help to Maintain L-Tryptophan Homeostasis in Tryptophan 2,3-Dioxygenase Knockout Mice

    Akihiro Maeta; Tsutomu Fukuwatari; Hiroshi Funakoshi; Toshikazu Nakamura; Katsumi Shibata

    2013-01-01

    We hypothesized that the requirements of essential nutrients are dependent upon catabolic abilities. Mice lacking L-tryptophan 2,3-dioxygenase (TDO) are available. The body concentration of L-tryptophan (L-Trp) has been reported to be higher in TDO-deficient mice than in wild-type (WT) mice. We examined the requirement of an appropriate L-Trp level for TDO-deficient mice using several biomarkers. TDO-deficient mice were fed a 10% amino-acid mixture diet containing 0.06%, 0.08%, and 0.17% L-Tr...

  12. Tryptophan metabolism in vitamin B6-deficient mice

    Bender, D A; Njagi, E. N.; Danielian, P. S.

    1990-01-01

    Vitamin B6 deficiency was induced in mice by maintenance for 4 weeks on a vitamin B6-free diet. Tryptophan metabolism was assessed by determining the urinary excretion of tryptophan metabolites, the metabolism of [14C]tryptophan in vivo and the formation of tryptophan and niacin metabolites by isolated hepatocytes. The vitamin B6-deficient animals excreted more xanthurenic acid and 3-hydroxykynurenine, and less of the niacin metabolites N1-methyl nicotinamide and methyl-2-pyridone-4-carboxami...

  13. Eosinophilic fasciitis associated with L-tryptophan ingestion.

    Hamilton, M. E.

    1991-01-01

    A 62 year old woman taking L-tryptophan developed eosinophilic fasciitis shortly after starting an exercise class. She received prednisone without benefit but improved after azathioprine treatment was started and L-tryptophan was discontinued. As products containing L-tryptophan have recently been implicated in development of the eosinophilia-myalgia syndrome it is suggested that the use of L-tryptophan might have contributed to the development of eosinophilic fasciitis in this patient. Simil...

  14. Tryptophan biosynthesis in the marine luminous bacterium Vibrio harveyi.

    Bieger, C D; I. P. Crawford

    1983-01-01

    Tryptophan biosynthetic enzyme levels in wild-type Vibrio harveyi and a number of tryptophan auxotrophs of this species were coordinately regulated over a 100-fold range of specific activities. The tryptophan analog indoleacrylic acid evoked substantial derepression of the enzymes in wild-type cells. Even higher enzyme levels were attained in auxotrophs starved for tryptophan, regardless of the location of the block in the pathway. A derepressed mutant selected by resistance to 5-fluorotrypto...

  15. Destruction of tryptophan during the aerobic oxidation of sulfite ions

    Tryptophan was rapidly destroyed aerobically in the presence of Mn2+ and sulfite. The rate of destruction was greatly increased when horseradish peroxidase was added. The optimal pH for the reaction was 8.0. The destruction of tryptophan was dependent on the aerobic oxidation of sulfite. Superoxide dismutase inhibited sulfite oxidation and thus inhibited the tryptophan destruction. Tracer studies using 14C indicate that tryptophan is converted into at least 4 products

  16. Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation.

    Maximova, Natalia; Antonio, Pizzol; Marilena, Granzotto; Rovere, Francesca; Tamaro, Paolo

    2015-01-01

    Varicella zoster virus (VZV), a threat for hematopoietic stem cell transplantation (HSCT) recipients, is still one of the most common viral pathogens that affect these patients with a reported incidence ranging between 17% and 50% in the post transplantation period. Valganciclovir (V-GCV), a valine ester pro-drug of GCV orally administrable, has recently shown great activity against CMV infections, but there are no reports of its clinical efficacy against VZV. We here report a case history of a patient with positive serologic test for VZV, who underwent allogeneic HSCT and developed an atypical varicella-like illness. First-line therapy with foscarnet had to be discontinued due rapid development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and therefore was switched to V-GCV. The renal impairment and skin lesions of the patient fully recovered after few days of therapy, even though the patient had complete lymphocyte depletion. This is the first case of a patient with chickenpox-like illness treated successfully with V-GCV. PMID:25131855

  17. Similarity in the acute cytotoxic response of mammalian cells to mercury (II) and x-rays: DNA damage and glutathione depletion

    Pronounced strand breakage of DNA analyzed elution techniques was produced in intact Chinese hamster ovary cells by 25 μM HgCl2 within 1 hr or 100 μM HgCl2 within 15 min. HgCl2-induced strand breakage was directly proportional to concentration up to 100 μM and to time within 1 hr. Levels of reduced glutathione decreased following HgCl2 in parallel with the induction of DNA strand breakage. Evidence is presented that this rapid and pronounced induction of DNA strand breaks and other cytotoxic responses following acute exposure to HgCl2 resembles the cellular effects of X-rays

  18. Requirement of young pigs for apparent ileal digestible tryptophan

    Schutte, J.B.; Verstraten, A.J.M.A.; Lenis, N.P.; Jong, de, P.; Diepen, van, C.A.

    1995-01-01

    In 5 growth trials with a total of 420 pigs, tryptophan requirements from 20 to 40 kg liveweight were estimated. L-Tryptophan 0, 0.15, 0.30, 0.45 and 0.60 g/kg was added to a basal diet containing tapioca, barley and maize, with CP 162 g/kg and tryptophan 1.65 g/kg. The control diet was supplemented with lysine, methionine plus cystine, threonine, isoleucine, valine and histidine to assure that only tryptophan was limiting pig performance. Diets were freely given as pellets. Total tryptophan ...

  19. Haploidentical Transplantation Without In Vitro T-Cell Depletion Results in Outcomes Equivalent to Those of Contemporaneous Matched Sibling and Unrelated Donor Transplantation for Acute Leukemia.

    Yu, Sijian; Fan, Qian; Sun, Jing; Fan, Zhiping; Zhang, Yu; Jiang, Qianli; Huang, Fen; Xuan, Li; Dai, Min; Zhou, Hongsheng; Liu, Hui; Liu, Qi-Fa

    2016-03-01

    The aim of the study is to determine whether HLA-haploidentical-related donor (HRD) transplant can achieve equivalent outcomes and have stronger GVL compared to HLA-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants.A total of 355 consecutive patients with acute leukemia undergoing allogeneic transplant at our single institute between March 2008 and March 2014 were enrolled in this retrospective investigation.Of the 355 patients, 96 cases received HRD, 153 MSD, and 106 MUD transplants. HRD transplant was associated with higher incidences of grade II to IV aGVHD (40.6%) compared with MSD (23.5%, P = 0.002) and MUD transplants (34.0%, P = 0.049), whereas incidences of grade III to IV aGVHD (11.4%, 7.8%, 10.5%, respectively; P = 0.590) and cGVHD (29.5%, 24.0%, 29.5%, respectively; P = 0.538) did not differ among 3 groups. Five-year relapse rates were 19.2%, 26.8%, and 23.0% in 3 groups, respectively (P = 0.419). However, of 206 high-risk patients, the relapse rate in HRD transplant was lower than in MSD transplant (23.8% vs 41.9%, P = 0.026). Multivariate analysis showed that HRD had beneficial impact on relapse (for MSD: P = 0.006). Five-year transplant-related mortality was lower in MSD transplant compared with those in HRD (17.3% vs 26.4%, P = 0.041) and MUD transplants (17.3% vs 24.1%, P = 0.037). Five-year overall survival were 60.4%, 64.6%, and 61.0%, respectively, in HRD, MSD, and MUD groups (P = 0.371); 5-year disease-free survival were 59.6%, 58.8%, and 54.9%, respectively (P = 0.423).Our results suggest that HRD transplant results in outcomes equivalent to MSD and MUD transplants. HRD might carry a superior GVL effect compared to MSD for high-risk patients. PMID:26986108

  20. Electron-impact-induced tryptophan molecule fragmentation

    In our investigation, we have studied the interactions of low-energy (<70 eV) electrons with tryptophan molecule belonging to the essential amino acids in order to probe the intrinsic properties of the molecule and trace its change(s) under the electron impact. The fragmentation of a gas-phase tryptophan molecule by low-energy electrons was studied both experimentally and theoretically. Various positively charged fragments were observed and analyzed. A special attention was paid to the energy characteristics of the ionic fragment yield. The geometrical parameters of the initial molecule rearrangement were also analyzed. The fragmentation observed was due to either a simple bond cleavage or more complex reactions involving molecular rearrangements

  1. Expression, Purification and Characterisation of Tryptophan Hydroxylases

    Windahl, Michael Skovbo

    2007-01-01

    og co-substratet tetrahydrobiopterin spalter dioxygen (O2) så det ene oxygen-atom indsættes i aminosyren tryptophan. Der findes to forskellige former af TPH: TPH-1 findes flere forskellige steder i kroppen, mens TPH-2 findes i hjernen hvor det har afgørende betydning for mængden af serotonin i...... tetrahydro-biopterin og O2. Denne opdagelse er meget vigtig for udvikling af lægemidler, som individuelt kan regulere TPH-1s eller TPH-2s enzymaktivitet. Desuden er det vist, at tryptophan binder til TPH før tetrahydrobiopterin og O2. Den 3-dimensionelle struktur af TPH-1 er bestemt ved brug af...

  2. Purification and Characterization of Tryptophan Hydroxylase

    Haahr, Lærke Tvedebrink; Christensen, Hans Erik Mølager

    2012-01-01

    Denne afhandling omhandler oprensning og karakterisering af jern enzymet tryptophanhydroxylase (TPH). TPH eksisterer i to isoformer, TPH1 og TPH2. Hver isoform består af 3 strukturelt forskellige domæner: det regulatoriske, det katalytiske og det tetrameriserende domæne. TPH katalyserer omdannelsen af tryptophan til 5-hydroxytryptophan, hvilket er det hastighedsbestemmende trin i biosyntesen af serotonin. Serotonin er en vigtig neurotransmitter, som er involveret i en række psykiske sygdommme...

  3. Tryptophan structure and dynamics using GROMOS

    The desire to use tryptophan as a fluorescent probe to study protein motion has motivated studies on tryptophan in aqueous solution. Tryptophan's biexponential fluorescence decay in solution has given rise to models which account for this behavior by postulating the existence of rotamers about the C/sub α/-C/sub β/ bond. These models require that the rotamers do not interconvert during the fluorescence lifetime; this assumption has not been verified. Further, there are certain peculiarities in assigning particular fluorescence lifetimes to these rotamers on the basis of proximity of the charged quenching groups. To address these issues the authors have used energy minimization and classical molecular dynamics as bases for transition rate and population estimates. These suggest that the C/sub β/-C/sub γ/ dihedral (chi/sub 2/) determines the fluorescence lifetime for equilibrating groups of C/sub α/-C/sub β/ rotamers. The energy minimization was similar to that already reported in the literature, but with GROMOS charges (for tryptophan in solution) and GROMOS interaction potentials. A potential surface for the energies of chi/sub 1/,chi/sub 2/ conformations was generated by constraining the dihedrals and minimizing the potential energy of the remaining degrees of freedom. Energy barriers between conformers range from about 3 kcal/mol to about 8 kcal/mol. The smaller barriers correspond to chi/sub 1/ rotations. Seven 100-psec classical dynamics trajectories were calculated for the system coupled to a heat bath with a time constant of 0.1 psec (solvent molecules are not explicityly included)

  4. DEPLETED URANIUM TECHNICAL WORK

    The Depleted Uranium Technical Work is designed to convey available information and knowledge about depleted uranium to EPA Remedial Project Managers, On-Scene Coordinators, contractors, and other Agency managers involved with the remediation of sites contaminated with this mater...

  5. A Mathematical Model of Tryptophan Metabolism via the Kynurenine Pathway Provides Insights into the Effects of Vitamin B-6 Deficiency, Tryptophan Loading, and Induction of Tryptophan 2,3-Dioxygenase on Tryptophan Metabolites123

    Rios-Avila, Luisa; Nijhout, H Frederik; Reed, Michael C.; SITREN, HARRY S.; Gregory, Jesse F.

    2013-01-01

    Vitamin B-6 deficiency is associated with impaired tryptophan metabolism because of the coenzyme role of pyridoxal 5′-phosphate (PLP) for kynureninase and kynurenine aminotransferase. To investigate the underlying mechanism, we developed a mathematical model of tryptophan metabolism via the kynurenine pathway. The model includes mammalian data on enzyme kinetics and tryptophan transport from the intestinal lumen to liver, muscle, and brain. Regulatory mechanisms and inhibition of relevant enz...

  6. Tryptophan availability modulates serotonin release from rat hypothalamic slices

    Schaechter, Judith D.; Wurtman, Richard J.

    1989-01-01

    The relationship between the tryptophan availability and serononin release from rat hypothalamus was investigated using a new in vitro technique for estimating rates at which endogenous serotonin is released spontaneously or upon electrical depolarization from hypothalamic slices superfused with a solution containing various amounts of tryptophan. It was found that the spontaneous, as well as electrically induced, release of serotonin from the brain slices exhibited a dose-dependent relationship with the tryptophan concentration of the superfusion medium.

  7. Tryptophan-Degrading Enzymes in Tumoral Immune Resistance

    van Baren, Nicolas; Van den Eynde, Benoît J

    2015-01-01

    Tryptophan is required for T lymphocyte effector functions. Its degradation is one of the mechanisms selected by tumors to resist immune destruction. Two enzymes, tryptophan-2,3-dioxygenase and indoleamine 2,3-dioxygenase 1, control tryptophan degradation through the kynurenine pathway. A third protein, indoleamine 2,3-dioxygenase 2, was identified more recently. All three enzymes were reported to be expressed in tumors, and are candidate targets for pharmacological inhibition aimed at restor...

  8. Radiolysis of aqueous-ethanolic solution of tryptophan

    The effect of ethanol on radiation stability of tryptophan during γ-irradiation of its aqueous solutions was investigated. In comparison with radiation losses of tryptophan irradiated in pure water, the losses in aqueous-ethanolic solutions are considerably higher and they increase with increasing ethanol concentration. Basic radiation products of tryptophan formed on irradiation of its aqueous-ethanolic solutions in consequence of the reaction of tryptophan with acetaldehyde as the main product of radiolysis of ethanol were followed by paper electrophoresis. (author)

  9. Gamma-radiolysis of aqueous solutions of tryptophan

    The nature of stable radiolytic products of tryptophan was investigated under different experimental conditions. Solutions of various tryptophan concentrations (10-2-10-4 mol dm-3) at pH 2 and 6.6 were analysed by paper and thin layer chromatography. In deaerated neutral solutions six products, which appeared to be invariant of initial tryptophan concentration, were observed. Chromatograms developed from deaerated solution at pH 2 revealed only one spot. In N2O-saturated solutions four products whose relative concentrations depended on the initial tryptophan concentration were observed. (author)

  10. Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human lumbar and cisternal cerebrospinal fluid.

    Young, S N; Gauthier, S.

    1981-01-01

    Tryptophan 5-hydroxyindoleacetic acid and indoleacetic acid were measured in cerebrospinal fluid taken during pneumoencephalography from patients, some of whom took a 3 g or 6 g tryptophan load at various times before. Measurements were made on both lumbar and cisternal cerebrospinal fluid and the results showed similarities between indoleamine metabolism in human brain and spinal cord. Our data suggested that (1) the blood-brain barrier active transport system for tryptophan is not far from ...

  11. Metabolism of an oral tryptophan load. II: Effect of pretreatment with the putative tryptophan pyrrolase inhibitors nicotinamide or allopurinol.

    Green, A. R.; Aronson, J K; Curzon, G; Woods, H F

    1980-01-01

    1 The effect of seven days administration of either allopurinol (300 mg daily) or nicotinamide (500 mg twice daily) on the metabolism of an oral L-tryptophan load (50 mg/kg) has been investigated. 2 Administration of either drug failed to alter the plasma total or free tryptophan or plasma kynurenine curve. Nor was the urinary excretion of tryptophan, kynurenine, 5-hydroxyindoleacetic acid or indole acetic acid influenced. 3 Allopurinol pretreatment did increase the volume of distribution of ...

  12. Depleted Uranium Management

    The paper considers radiological and toxic impact of the depleted uranium on the human health. Radiological influence of depleted uranium is less for 60 % than natural uranium due to the decreasing of short-lived isotopes uranium-234 and uranium-235 after enrichment. The formation of radioactive aerosols and their impact on the human are mentioned. Use of the depleted uranium weapons has also a chemical effect on intake due to possible carcinogenic influence on kidney. Uranium-236 in the substance of the depleted uranium is determined. The fact of beta-radiation formation in the uranium-238 decay is regarded. This effect practically is the same for both depleted and natural uranium. Importance of toxicity of depleted uranium, as the heavier chemical substance, has a considerable contribution to the population health. The paper analyzes risks regarding the use of the depleted uranium weapons. There is international opposition against using weapons with depleted uranium. Resolution on effects of the use of armaments and ammunitions containing depleted uranium was five times supported by the United Nations (USA, United Kingdom, France and Israel did not support). The decision for banning of depleted uranium weapons was supported by the European Parliament

  13. Chemical Modification of Tryptophan Residues in Pullulanase

    2005-01-01

    Tryptophan(Trp)residues in pullulanase have been chemically modified with N-bromossuccinimide(NBS). The results of ultraviolet spectra indicated that there are 18 Trp residues in pullulanase and nine of them are located on the surface of the enzyme. Three of these Trp residues are none-essential residues which showed the fastest reaction speed by Zhou's plot. Two of the seven relative faster reacting residues are essential for the activity of the enzyme. The other eight are none-reactive residues with lowest reaction speed.

  14. One-step of tryptophan attenuator inactivation and promoter swapping to improve the production of L-tryptophan in Escherichia coli

    Gu Pengfei; Yang Fan; Kang Junhua; Wang Qian; Qi Qingsheng

    2012-01-01

    Abstract Background L-tryptophan is an aromatic amino acid widely used in the food, chemical and pharmaceutical industries. In Escherichia coli, L-tryptophan is synthesized from phosphoenolpyruvate and erythrose 4-phosphate by enzymes in the shikimate pathway and L-tryptophan branch pathway, while L-serine and phosphoribosylpyrophosphate are also involved in L-tryptophan synthesis. In order to construct a microbial strain for efficient L-tryptophan production from glucose, we developed a one ...

  15. Characterisation of the tryptophan synthase alpha subunit in maize

    Gierl Alfons

    2008-04-01

    Full Text Available Abstract Background In bacteria, such as Salmonella typhimurium, tryptophan is synthesized from indole-3-glycerole phosphate (IGP by a tryptophan synthase αββα heterotetramer. Plants have evolved multiple α (TSA and β (TSB homologs, which have probably diverged in biological function and their ability of subunit interaction. There is some evidence for a tryptophan synthase (TS complex in Arabidopsis. On the other hand maize (Zea mays expresses the TSA-homologs BX1 and IGL that efficiently cleave IGP, independent of interaction with TSB. Results In order to clarify, how tryptophan is synthesized in maize, two TSA homologs, hitherto uncharacterized ZmTSA and ZmTSAlike, were functionally analyzed. ZmTSA is localized in plastids, the major site of tryptophan biosynthesis in plants. It catalyzes the tryptophan synthase α-reaction (cleavage of IGP, and forms a tryptophan synthase complex with ZmTSB1 in vitro. The catalytic efficiency of the α-reaction is strongly enhanced upon complex formation. A 160 kD tryptophan synthase complex was partially purified from maize leaves and ZmTSA was identified as native α-subunit of this complex by mass spectrometry. ZmTSAlike, for which no in vitro activity was detected, is localized in the cytosol. ZmTSAlike, BX1, and IGL were not detectable in the native tryptophan synthase complex in leaves. Conclusion It was demonstrated in vivo and in vitro that maize forms a tryptophan synthase complex and ZmTSA functions as α-subunit in this complex.

  16. Destabilization of artificial biomembrane induced by the penetration of tryptophan

    The effect of tryptophan on the membrane stability was studied by using three artificial biological membranes including liposome, Langmuir monolayer and solid supported bilayer lipid membrane (s-BLM) as models. All the results indicate that the penetration of tryptophan can destabilize different artificial biological membranes. The diameter of liposome and the leakage of calcein from liposome increased with the increase of tryptophan concentration because the penetration of tryptophan was beneficial for dehydrating the polar head groups of lipids and the formation of fusion intermediates. π-A isotherms of lecithin on the subphase of tryptophan solution further confirm that tryptophan can penetrate into lipid monolayer and reduce the stability of lipid monolayer. When the concentration of tryptophan increased from 0 to 2 x 10-3 mol L-1, the limiting molecular area of lecithin increased from 110.5 to 138.5 A2, but the collapse pressure of the monolayer decreased from 47.6 to 42.3 mN m-1, indicating the destabilization of lipid monolayer caused by the penetration of tryptophan. The resistance spectra of s-BLM demonstrate that the existence of tryptophan leads to the formation of some defects in s-BLM and the destabilization of s-BLM. The values of electron-transfer resistance and double layer capacitance respectively decreased from 5.765 x 106 Ω and 3.573 x 10-8 F to 1.391 x 106 Ω and 3.340 x 10-8 F when the concentration of tryptophan increased from 0 to 2 x 10-3 mol L-1. Correspondingly, the breakdown voltage of s-BLM decreased from 2.51 to 1.72 V.

  17. Depleted uranium in Japan

    In Japan, depleted uranium ammunition is regarded as nuclear weapons and meets with fierce opposition. The fact that US Marines mistakenly fired bullets containing depleted uranium on an island off Okinawa during training exercises in December 1995 and January 1996, also contributes. The overall situation in this area in Japan is outlined. (P.A.)

  18. Management of depleted uranium

    Large stocks of depleted uranium have arisen as a result of enrichment operations, especially in the United States and the Russian Federation. Countries with depleted uranium stocks are interested in assessing strategies for the use and management of depleted uranium. The choice of strategy depends on several factors, including government and business policy, alternative uses available, the economic value of the material, regulatory aspects and disposal options, and international market developments in the nuclear fuel cycle. This report presents the results of a depleted uranium study conducted by an expert group organised jointly by the OECD Nuclear Energy Agency and the International Atomic Energy Agency. It contains information on current inventories of depleted uranium, potential future arisings, long term management alternatives, peaceful use options and country programmes. In addition, it explores ideas for international collaboration and identifies key issues for governments and policy makers to consider. (authors)

  19. Water Depletion Threatens Agriculture

    Brauman, K. A.; Richter, B. D.; Postel, S.; Floerke, M.; Malsy, M.

    2014-12-01

    Irrigated agriculture is the human activity that has by far the largest impact on water, constituting 85% of global water consumption and 67% of global water withdrawals. Much of this water use occurs in places where water depletion, the ratio of water consumption to water availability, exceeds 75% for at least one month of the year. Although only 17% of global watershed area experiences depletion at this level or more, nearly 30% of total cropland and 60% of irrigated cropland are found in these depleted watersheds. Staple crops are particularly at risk, with 75% of global irrigated wheat production and 65% of irrigated maize production found in watersheds that are at least seasonally depleted. Of importance to textile production, 75% of cotton production occurs in the same watersheds. For crop production in depleted watersheds, we find that one half to two-thirds of production occurs in watersheds that have not just seasonal but annual water shortages, suggesting that re-distributing water supply over the course of the year cannot be an effective solution to shortage. We explore the degree to which irrigated production in depleted watersheds reflects limitations in supply, a byproduct of the need for irrigation in perennially or seasonally dry landscapes, and identify heavy irrigation consumption that leads to watershed depletion in more humid climates. For watersheds that are not depleted, we evaluate the potential impact of an increase in irrigated production. Finally, we evaluate the benefits of irrigated agriculture in depleted and non-depleted watersheds, quantifying the fraction of irrigated production going to food production, animal feed, and biofuels.

  20. Increased Tryptophan Catabolism is Associated with Increased Frequency of CD161+Tc17/MAIT Cells, and Lower CD4+ T cell Count in HIV-1 infected Patients on cART after Two Years of Follow-up

    Gaardbo, Julie Christine; Trøseid, Marius; Stiksrud, Birgitte;

    2015-01-01

    BACKGROUND: HIV infection is associated with increased ratio between kynurenine and tryptophan (KTR) in plasma, increased microbial translocation, expansion of Tregs and depletion of Tc17/mucosa associated invariant T cells (MAIT) cells. The association between these parameters and the impact of ...

  1. Photochemical hydrogen-deuterium exchange reaction of tryptophan: the role in nonradiative decay of singlet tryptophan

    The mechanism of nonradiative decay of singlet excited tryptophan (Trp) in aqueous solution was investigated by a highly selective photosubstitution of the C-4 hydrogen of Trp with deuterium of solvent D2O. It was concluded that intramolecular proton transfer from the α-ammonia group giving rise to formation of a protonated species plays an important role in the nonradiative decay of singlet Trp at neutral pH. 11 references, 1 figure

  2. The azide radical and its reaction with tryptophan and tyrosine

    Azide radicals react with azide ions according to N3 + N3- N6-, K = 0.33 dm3 mol-1. The species N6- has an absorption maximum at 645 nm epsilon = 6600 dm3 mol-1 cm-1. The reaction between the azide radical and ferrocyanide at an azide concentration of 0.05 mol dm-3 is independent of ionic strength, showing that N3 is the reacting form of the radical. From the reduction potentials of the azide radical and tryptophan, azide radicals can react with tryptophan by electron transfer. Reaction of azide radicals with tyrosine can also proceed by electron transfer. Whereas the formation of the tryptophan radical cation can be demonstrated in the reaction of Br2- with tryptophan, its formation could not be observed directly in the reaction of N3 with tryptophan because the azide ion deprotonates the tryptophan radical cation at high concentrations of azide. Reactions are proposed to account for observations made in previous pulse radiolysis studies of solutions containing azide and tryptophan or tyrosine. (author)

  3. Lattice Raman scattering in gamma-irradiated tryptophan crystals

    The character of change in lattice Raman spectra of aromatic aminoacid crystals-D-tryptophan - under the effect of gamma radiation has been traced. The choice of aromatic aminoacid as object for investigation is related to assumed high sensitivity of tryptophan crystal structure to the effect of short-wave irradiation due to the presence of a great number of protons in it, which interect intensively with gamma quanta. Considerable change in lattice Raman spectrum of D-tryptophan crystals under the effect of small doses of gamma irradiation has been revealed

  4. Radiation induced decomposition of tryptophan in deaerated aqueous solutions

    The effect of absorbed dose on the decomposition of tryptophan under gamma irradiation has been investigated. Neutral deaerated and N2O saturated solutions of various tryptophan concentrations were analysed. In both cases the decomposition yield of tryptophan decreases as irradiation dose increases. From the observed dependence initial yields G0(-Trp) = 3.35 and 4.75 were estimated for deaerated and N2O saturated solutions respectively. Estimated initial yields are in good agreement with values calculated according to the reaction scheme proposed. (author)

  5. Modelling the evolution of the archaeal tryptophan synthase

    Merkl Rainer

    2007-01-01

    Abstract Background Microorganisms and plants are able to produce tryptophan. Enzymes catalysing the last seven steps of tryptophan biosynthesis are encoded in the canonical trp operon. Among the trp genes are most frequently trpA and trpB, which code for the alpha and beta subunit of tryptophan synthase. In several prokaryotic genomes, two variants of trpB (named trpB1 or trpB2) occur in different combinations. The evolutionary history of these trpB genes is under debate. Results In order to...

  6. A conserved suppressor mutation in a tryptophan auxotroph results in dysregulation of Pseudomonas quinolone signal synthesis.

    Knoten, Claire A; Wells, Greg; Coleman, James P; Pesci, Everett C

    2014-07-01

    Pseudomonas aeruginosa is a common nosocomial pathogen that relies on three cell-to-cell signals to regulate multiple virulence factors. The Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4-quinolone) is one of these signals, and it is known to be important for P. aeruginosa pathogenesis. PQS is synthesized in a multistep reaction that condenses anthranilate and a fatty acid. In P. aeruginosa, anthranilate is produced via the kynurenine pathway and two separate anthranilate synthases, TrpEG and PhnAB, the latter of which is important for PQS synthesis. Others have previously shown that a P. aeruginosa tryptophan auxotroph could grow on tryptophan-depleted medium with a frequency of 10(-5) to 10(-6). These revertants produced more pyocyanin and had increased levels of phnA transcript. In this study, we constructed similar tryptophan auxotroph revertants and found that the reversion resulted from a synonymous G-to-A nucleotide mutation within pqsC. This change resulted in increased pyocyanin and decreased PQS, along with an increase in the level of the pqsD, pqsE, and phnAB transcripts. Reporter fusion and reverse transcriptase PCR studies indicated that a novel transcript containing pqsD, pqsE, and phnAB occurs in these revertants, and quantitative real-time PCR experiments suggested that the same transcript appears in the wild-type strain under nutrient-limiting conditions. These results imply that the PQS biosynthetic operon can produce an internal transcript that increases anthranilate production and greatly elevates the expression of the PQS signal response protein PqsE. This suggests a novel mechanism to ensure the production of both anthranilate and PQS-controlled virulence factors. PMID:24748618

  7. Uses of depleted uranium

    The depleted uranium is that in which percentage of uranium-235 fission executable is less than 0.2% or 0.3%. It is usually caused by the process of reprocessing the nuclear fuel burning, and also mixed with some other radioactive elements such as uranium 236, 238 and plutonium 239. The good features of the depleted uranium are its high density, low price and easily mined. So, the specifications for depleted uranium make it one of the best materials in case you need to have objects small in size, but quite heavy regarding its size. Uses of deplet ed uranium were relatively increased in domestic industrial uses as well as some uses in nuclear industry in the last few years. So it has increased uses in many areas of military and peaceful means such as: in balancing the giant air crafts, ships and missiles and in the manufacture of some types of concrete with severe hardness. (author)

  8. Molecular Mechanism of Tryptophan-Dependent Transcriptional Regulation in Chlamydia trachomatis

    Akers, Johnny C.; Tan, Ming

    2006-01-01

    Tryptophan is an essential amino acid that is required for normal development in Chlamydia species, and tryptophan metabolism has been implicated in chlamydial persistence and tissue tropism. The ability to synthesize tryptophan is not universal among the Chlamydiaceae, but species that have a predicted tryptophan biosynthetic pathway also encode an ortholog of TrpR, a regulator of tryptophan metabolism in many gram-negative bacteria. We show that in Chlamydia trachomatis serovar D, TrpR regu...

  9. A Jerte Valley Cherry-Based Product as a Supply of Tryptophan

    Paredes, Sergio D.; Carmen Barriga; Juan. I Maynar-Mariño; Javier Cubero; Antonio F. Toribio-Delgado; Javier Espino; María Garrido; Rodríguez, Ana B.

    2012-01-01

    L-Tryptophan (tryptophan) is an essential amino acid in humans. It has important roles as a precursor of different bioactive compounds. Based on previous studies in which tryptophan has been shown to be present in fresh cherries, the aim of the present work was to analyze the tryptophan content of a Jerte Valley cherry-based product. A previously optimized method of analysis of tryptophan was used, ie, high-performance liquid chromatography with fluorescence detection (HPLC/FL). As expected, ...

  10. Tryptophan Properties in Fluorescence and Functional Stability of Plasminogen Activator Inhibitor 1

    Verheyden, Stefan; Sillen, Alain; Gils, Ann; Paul J Declerck; Engelborghs, Yves

    2003-01-01

    Plasminogen activator inhibitor 1 harbors four tryptophan residues at positions 86, 139, 175, and 262. To investigate the contribution of each tryptophan residue to the total fluorescence and to reveal the mutual interactions of the tryptophan residues and interactions with the other amino acids, 15 mutants in which tryptophan residues have been replaced by phenylalanines were constructed, purified, and characterized. Conformational distribution analysis revealed that the tryptophan mutants h...

  11. Molecular mechanism of tryptophan-dependent transcriptional regulation in Chlamydia trachomatis

    Akers, Johnny C.; Tan, Ming

    2006-01-01

    Tryptophan is an essential amino acid that is required for normal development in Chlamydia species, and tryptophan metabolism has been implicated in chlamydial persistence and tissue tropism. The ability to synthesize tryptophan is not universal among the Chlamydiaceae, but species that have a predicted tryptophan biosynthetic pathway also encode an ortholog of TrpR, a regulator of tryptophan metabolism in many gram-negative bacteria. We show that in Chlamydia trachomatis serovar D, TrpR regu...

  12. Tryptophan rich diet as a new approach to study the serotoninergic enteropancreatic axis.

    Goke, B; Richter, G.; Keim, V.; Arnold, R.

    1987-01-01

    The influence of a tryptophan enriched diet (L-tryptophan added as 1% of total diet), fed over 10 days, on the rat duodenum and pancreas was studied by immunohistology, measurements of serotonin and tryptophan tissue concentrations by HPLC, and incubations of pancreatic lobules. Ingestion of a tryptophan enriched diet resulted in increased contents of tryptophan and serotonin in the duodenum that was not accompanied by a significant change of the serotonin cell density. Neither basal nor CCK-...

  13. Depleted uranium during the Kosovo war

    Using the depleted uranium (DU) in the war and civil aims is considered. There are characterized the head parts of projectiles (drifts) from DU, used during Balkan wars, are described. The uranium isotope activity and exposure dose rates from β, γ and photon radiation of the drifts are investigated. The content of uranium and plutonium isotopes in the soil samples are measured. It is concluded that DU cannot exercise the acute influence on the health of military man and civil population

  14. Tryptophan and ATTO 590: Mutual Fluorescence Quenching and Exciplex Formation

    Bhattacharjee, Ujjal [Ames Laboratory; Beck, Christie [Ames Laboratory; Winter, Arthur [Iowa State University; Wells, Carson [Iowa State University; Petrich, Jacob W [Ames Laboratory

    2014-07-24

    Investigation of fluorescence quenching of probes, such as ATTO dyes, is becoming an increasingly important topic owing to the use of these dyes in super-resolution microscopies and in single-molecule studies. Photoinduced electron transfer is their most important nonradiative pathway. Because of the increasing frequency of the use of ATTO and related dyes to investigate biological systems, studies are presented for inter- and intramolecular quenching of ATTO 590 with tryptophan. In order to examine intramolecular quenching, an ATTO 590–tryptophan conjugate was synthesized. It was determined that tryptophan is efficiently quenching ATTO 590 fluorescence by excited-state charge transfer and two charge transfer complexes are forming. In addition, it was discovered that an exciplex (whose lifetime is 5.6 ns) can be formed between tryptophan and ATTO 590, and it is suggested that the possibility of such exciplex formation should be taken into account when protein fluorescence is monitored in a system tagged with ATTO dyes.

  15. Inhibition of tryptophan pyrrolase activity in restraint female rats following medroxyproge-sterone administration

    To determine the effects of Medroxyprogesterone (hormonal contraceptive) in restraint stressed female rats in relation to tryptophan metabolism. Female Albino Wistar rats (150-200 gm body wt) were selected and divided into four groups (n=5 in each group). Rats were injected intraperitoneally either vehicle or Medroxyprogesterone (25mg/kg/ml) and were immediately subjected to 2 hours restraint stress while respective controls remained in their home cages. In restraint stress group, hepatic holo and total tryptophan pyrrolase activities were increased. Liver tryptophan, total serum tryptophan and albumin concentration were decreased. Brain tryptophan, 5HT and 5HIAA concentrations were increased. Medroxyprogesterone administration in unrestraint rats inhibited holo, total and apo enzyme activities with increases in liver tryptophan concentrations. Effect of restraint stress following Medroxyprogesterone administration when compared with drug injected unrestrained group showed increase in holo and total tryptophan pyrrolase activities with decrease in liver tryptophan concentrations. Brain tryptophan, 5HT and 5HIAA levels were increased. Results when compared with vehicle injected stressed-rats showed that total and apo tryptophan pyrrolase activities were decreased. Liver tryptophan, serum tryptophan and albumin concentrations were increased but brain tryptophan metabolism was not effected. It is concluded that Medroxyprogesterone inhibits stress induce increases in peripheral tryptophan metabolism and increases plasma tryptophan. Although stress induced increases in brain indoles were not effected by the drug at two hours, further studies on time course effects of this drug will be needed to explore its possible anxiolytic effects. (author)

  16. Digestible tryptophan:lysine ratio for laying hens

    Matheus Ramalho de Lima

    2012-10-01

    Full Text Available The objective of this study was to evaluate the requirement of digestible tryptophan for white laying hens in the production stage fed diets of different digestible tryptophan:digestible lysine ratios, as well as animal performance and histological alterations in their reproductive and digestive systems. A total of 280 white laying hens at 29 weeks of age were distributed in a completely randomized design with five treatments and seven replications with eight birds in each. The treatments consisted of a base feed, formulated with corn, soybean meal and corn gluten meal, and supplemented with the synthetic amino acids L-lysine, DL-methionine, L-threonine, L-isoleucine, L-arginine, and L-valine, so as to meet the nutritional requirements for laying hens, except for digestible tryptophan. The basal diet was supplemented with 0.00; 0.017; 0.035; 0.052; and 0.069 g/kg of L-tryptophan in substitution for corn starch with the objective of reaching the levels of 0.151; 0.167; 0.183; 0.199; and 0.215 g/kg of digestible tryptophan in the feed. For the ratio between digestible amino acids and lysine, the recommendation of Brazilian Tables for Poultry and Swine was followed, except for the digestible tryptophan:digestible lysine ratios, which were 19, 21, 23, 25 and 27 for each treatment. The variation in the digestible tryptophan:digestible lysine ratio promoted changes in performance and in the histological characteristics, improving the results. The digestible tryptophan:digestible lysine ratio of 24.5% in the feed of white laying hens in production stage promotes better animal performance and histological results.

  17. Stabilization of lignin peroxidases in white rot fungi by tryptophan.

    Collins, P. J.; Field, J. A.; Teunissen, P; Dobson, A D

    1997-01-01

    Supplementation of various cultures of white rot fungi with tryptophan was found to have a large stimulatory effect on lignin peroxidase activity levels. This enhancement was greater than that observed in the presence of the lignin peroxidase recycling agent veratryl alcohol. Using reverse transcription-PCR, we found that tryptophan does not act to induce lignin peroxidase expression at the level of gene transcription. Instead, the activity enhancement observed is likely to result from the pr...

  18. Kernel modifications and tryptophan content in QPM segregating generations

    -Ignjatović-Micić Dragana

    2010-01-01

    Full Text Available Maize has poor nutritional value due to deficiency of two essential amino acids - tryptophan and lysine. Although recessive opaque2 (o2 mutation significantly increases their content in the endosperm, incorporation of opaque2 into high yielding cultivars was not commercially successful, because of its numerous agronomic and processing problems due to soft endosperm. Quality protein maize - QPM has lately been introduced as opaque2 maize with improved endosperm hardness and improved agronomic traits, but mostly within tropical and subtropical germplasm. The ongoing breeding project at MRI includes improvement of MRI opaque2 lines and conversion of standard lines to QPM germplasm. The main selection steps in QPM breeding involve assessing kernel modifications and tryptophan level in each generation. Herein, we present the results of the analysis for these traits on F3 and BC1F1 generations of QPM x opaque2, opaque2 x QPM and standard lines x QPM crosses. The results showed that the majority the genotypes had kernel types 2 and 3 (good modifications. The whole grain tryptophan content in F3 and BC1F1 genotypes of crosses between QPM and opaque2 germplasm was at the quality protein level, with a few exceptions. All BC1F1 genotypes of standard lines x QPM had tryptophan content in the range of normal maize, while majority of F3 genotypes had tryptophan content at level of QPM. The progeny (with increased tryptophan levels of QPM and opaque2 crosses had significantly higher tryptophan content compared to the progeny of crosses between standard and QPM lines - 0.098 to 0.114 and 0.080, respectively. All genotypes that had poorly modified kernels and/or low tryptophan content will be discarded from further breeding.

  19. Conformational Effects on Tryptophan Fluorescence in Cyclic Hexapeptides

    Pan, Chia-Pin; Barkley, Mary D.

    2004-01-01

    The peptide bond quenches tryptophan fluorescence by excited-state electron transfer, which probably accounts for most of the variation in fluorescence intensity of peptides and proteins. A series of seven peptides was designed with a single tryptophan, identical amino acid composition, and peptide bond as the only known quenching group. The solution structure and side-chain χ1 rotamer populations of the peptides were determined by one-dimensional and two-dimensional 1H-NMR. All peptides have...

  20. Tryptophan rotamer distributions in amphipathic peptides at a lipid surface.

    Clayton, A H; Sawyer, W. H.

    1999-01-01

    The fluorescence decay of tryptophan is a sensitive indicator of its local environment within a peptide or protein. We describe the use of frequency domain fluorescence spectroscopy to determine the conformational and environmental changes associated with the interaction of single tryptophan amphipathic peptides with a phospholipid surface. The five 18-residue peptides studied are based on a class A amphipathic peptide known to associate with lipid bilayers. The peptides contain a single tryp...

  1. Tryptophan Transport in Human Fibroblast Cells—A Functional Characterization

    Vumma Ravi; Johansson Jessica; Lewander Tommy; Venizelos Nikolaos

    2011-01-01

    There are indications that serotonergic neurotransmission is disturbed in several psychiatric disorders. One explanation may be disturbed transport of tryptophan (precursor for serotonin synthesis) across cell membranes. Human fibroblast cells offer an advantageous model to study the transport of amino acids across cell membranes, since they are easy to propagate and the environmental factors can be controlled. The aim of this study was to functionally characterize tryptophan transport and to...

  2. Synthesis of [α-15N]-dl-tryptophan

    [α-15N]-dl-tryptophan was synthesized by the use of Al-Ni alloy catalytic hydrogenation from 15N-glycine via several steps. The overall yield of the final product was 46.9% and the abundance of 15N was about 93%. The physicochemical properties of the synthetic compound obtained were the same as those of the standard tryptophan. Its structure were confirmed by the elemental analyses, MS, UV and paper chromatography

  3. Role of Tryptophan Residues in Gramicidin Channel Organization and Function

    Chattopadhyay, Amitabha; RAWAT, SATINDER S.; Greathouse, Denise V.; Kelkar, Devaki A.; Koeppe, Roger E.

    2008-01-01

    The linear peptide gramicidin forms prototypical ion channels specific for monovalent cations and has been used extensively to study the organization, dynamics, and function of membrane-spanning channels. The tryptophan residues in gramicidin channels are crucial for maintaining the structure and function of the channel. We explored the structural basis for the reduction in channel conductance in the case of single-tryptophan analogs of gramicidin with three Trp → hydrophobic substitutions us...

  4. Carbon dots from tryptophan doped glucose for peroxynitrite sensing

    Highlights: • Synthesis of tryptophan doped carbon dots. • Experimental design optimization of the tryptophan doped carbon dots synthesis. • Fluorescence sensing of peroxynitrite by tryptophan doped carbon dots. • Peroxynitrite quantification in serum samples by tryptophan doped carbon dots. - Abstract: Tryptophan doped carbon dots (Trp-CD) were microwave synthesized. The optimum conditions of synthesizing of the Trp-CD were established by response surface multivariate optimization methodologies and were the following: 2.5 g of glucose and 300 mg of tryptophan diluted in 15 mL of water exposed for 5 min to a microwave radiation of 700 W. Trp-CD have an average size of 20 nm, were fluorescent with a quantum yield of 12.4% and the presence of peroxynitrite anion (ONOO−) provokes quenching of the fluorescence. The evaluated analytical methodology for ONOO− detection shows a linear response range from 5 to 25 μM with a limit of detection of 1.5 μM and quantification of 4.9 μM. The capability of the ONOO− quantification was evaluated in standard solutions and in fortified serum samples

  5. Carbon dots from tryptophan doped glucose for peroxynitrite sensing

    Simões, Eliana F.C. [CIQ-UP, Grupo de Ciências Biológicas e Bioanalíticas, Faculdade de Farmácia da Universidade de Coimbra, Pólo das Ciências da Saúde, 3000-548 Coimbra (Portugal); CIQ-UP, Departamento de Química, Faculdade de Ciências da Universidade do Porto, R. Campo Alegre 687, 4169-007 Porto (Portugal); Esteves da Silva, Joaquim C.G. [CIQ-UP, Departamento de Química, Faculdade de Ciências da Universidade do Porto, R. Campo Alegre 687, 4169-007 Porto (Portugal); Leitão, João M.M., E-mail: jleitao@ff.uc.pt [CIQ-UP, Grupo de Ciências Biológicas e Bioanalíticas, Faculdade de Farmácia da Universidade de Coimbra, Pólo das Ciências da Saúde, 3000-548 Coimbra (Portugal)

    2014-12-10

    Highlights: • Synthesis of tryptophan doped carbon dots. • Experimental design optimization of the tryptophan doped carbon dots synthesis. • Fluorescence sensing of peroxynitrite by tryptophan doped carbon dots. • Peroxynitrite quantification in serum samples by tryptophan doped carbon dots. - Abstract: Tryptophan doped carbon dots (Trp-CD) were microwave synthesized. The optimum conditions of synthesizing of the Trp-CD were established by response surface multivariate optimization methodologies and were the following: 2.5 g of glucose and 300 mg of tryptophan diluted in 15 mL of water exposed for 5 min to a microwave radiation of 700 W. Trp-CD have an average size of 20 nm, were fluorescent with a quantum yield of 12.4% and the presence of peroxynitrite anion (ONOO{sup −}) provokes quenching of the fluorescence. The evaluated analytical methodology for ONOO{sup −} detection shows a linear response range from 5 to 25 μM with a limit of detection of 1.5 μM and quantification of 4.9 μM. The capability of the ONOO{sup −} quantification was evaluated in standard solutions and in fortified serum samples.

  6. Regulation of tryptophan operon expression in the archaeon Methanothermobacter thermautotrophicus.

    Xie, Yunwei; Reeve, John N

    2005-09-01

    Conserved trp genes encode enzymes that catalyze tryptophan biosynthesis in all three biological domains, and studies of their expression in Bacteria and eukaryotes have revealed a variety of different regulatory mechanisms. The results reported here provide the first detailed description of an archaeal trp gene regulatory system. We have established that the trpEGCFBAD operon in Methanothermobacter thermautotrophicus is transcribed divergently from a gene (designated trpY) that encodes a tryptophan-sensitive transcription regulator. TrpY binds to TRP box sequences (consensus, TGTACA) located in the overlapping promoter regions between trpY and trpE, inhibiting trpY transcription in the absence of tryptophan and both trpY and trpEGCFBAD transcription in the presence of tryptophan. TrpY apparently inhibits trpY transcription by blocking RNA polymerase access to the site of trpY transcription initiation and represses trpEGCFBAD transcription by preventing TATA box binding protein (TBP) binding to the TATA box sequence. Given that residue 2 (W2) is the only tryptophan in TrpY and in TrpY homologues in other Euryarchaea and that there is only one tryptophan codon in the entire trpEGCFBAD operon (trpB encodes W175), expression of the trp operon may also be regulated in vivo by the supply of charged tRNA(Trp) available to translate the second codon of the trpY mRNA. PMID:16159776

  7. Complexity in regulation of tryptophan biosynthesis in Bacillus subtilis.

    Gollnick, Paul; Babitzke, Paul; Antson, Alfred; Yanofsky, Charles

    2005-01-01

    Bacillus subtilis uses novel regulatory mechanisms in controlling expression of its genes of tryptophan synthesis and transport. These mechanisms respond to changes in the intracellular concentrations of free tryptophan and uncharged tRNA(Trp). The major B. subtilis protein that regulates tryptophan biosynthesis is the tryptophan-activated RNA-binding attenuation protein, TRAP. TRAP is a ring-shaped molecule composed of 11 identical subunits. Active TRAP binds to unique RNA segments containing multiple trinucleotide (NAG) repeats. Binding regulates both transcription termination and translation in the trp operon, and translation of other coding regions relevant to tryptophan metabolism. When there is a deficiency of charged tRNA(Trp), B. subtilis forms an anti-TRAP protein, AT. AT antagonizes TRAP function, thereby increasing expression of all the genes regulated by TRAP. Thus B. subtilis and Escherichia coli respond to identical regulatory signals, tryptophan and uncharged tRNA(Trp), yet they employ different mechanisms in regulating trp gene expression. PMID:16285852

  8. Synthesis of [3-14C]-L-tryptophan and 5'-hydroxy-[3-14C]-L-tryptophan

    The synthesis of selectively labeled [3-14C]-L-tryptophan and its derivative 5'-hydroxy-[3-14C]-L-tryptophan using chemical and multienzymatic methods is reported. The key intermediate for this synthesis, 3-14C]-DL-alanine was obtained from 14CH3I as a result of its condensation with N- (diphenylmethylene)glycine tert-butyl ester. Next, the mixture containing [3-14C]-DL-alanine, indole or 5-hydroxyindole has been converted to [3-14C]-L-tryptophan or 5'-hydroxy-[3-14C]-L-tryptophan, respectively, in a one-pot multienzymatic reaction using four enzymes: -amino acid oxidase, catalase, glutamic-pyruvic transaminase and tryptophanase. (author)

  9. Flavin-dependent Tryptophan Halogenases and Their Use in Formation of Novel Tryptophan Derived Compounds

    CHEN Xian-Ping; HUANG Mei-Fa; WANG Bin

    2008-01-01

    Ravin-dependent halogenases are now known to play a significant role in the introduction of chloride and bro- mide into activated organic molecules. Herein a new strategy was reported to formate monodechloroaminopyrrolni-trin derivative 3-(2-amino-4-chlorophenyl)pyrrole, which is a key intermediate for the analysis and mutagenesis of pyrrolnitrin biosynthesis, by combinatorial biosynthesis using regioselective tryptophan halogenases. The successful production in Pseudomonas, with combinatorial cultivating method, demonstrates the feasibility of the new ap-proach to modify and analyze these important secondary metabolite pathways.

  10. Antarctic ozone depletion

    Antarctic ozone depletion is most severe during the southern hemisphere spring, when the local reduction in the column amount may be as much as 50 percent. The extent to which this ozone poor air contributes to the observed global ozone loss is a matter of debate, but there is some evidence that fragments of the 'ozone hole' can reach lower latitudes following its breakup in summer. Satellite data show the seasonal evolution of the ozone hole. A new dimension has been added to Antarctic ozone depletion with the advent of large volcanic eruptions such as that from Mount Pinatubo in 1991. (author). 5 refs., 1 fig

  11. Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies

    Introduction: Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. Methods: Dynamic α-[11C]methyl-L-tryptophan (AMT) PET was performed in nine women with stage II–IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. Results: Tumor AMT uptake peaked at 5–20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6–9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P < .01). Invasive ductal carcinomas (n = 6) showed particularly high AMT SUVs (range, 4.7–9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. Conclusions: Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5–20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.

  12. Kynurenine pathway in psychosis: evidence of increased tryptophan degradation.

    Barry, Sandra

    2009-05-01

    The kynurenine pathway of tryptophan degradation may serve to integrate disparate abnormalities heretofore identified in research aiming to elucidate the complex aetiopathogenesis of psychotic disorders. Post-mortem brain tissue studies have reported elevated kynurenine and kynurenic acid in the frontal cortex and upregulation of the first step of the pathway in the anterior cingulate cortex of individuals with schizophrenia. In this study, we examined kynurenine pathway activity by measuring tryptophan breakdown, a number of pathway metabolites and interferon gamma (IFN-gamma), which is the preferential activator of the first-step enzyme, indoleamine dioxygenase (IDO), in the plasma of patients with major psychotic disorder. Plasma tryptophan, kynurenine pathway metabolites were measured using high-performance liquid chromatography (HPLC) in 34 patients with a diagnosis on the psychotic spectrum (schizophrenia or schizoaffective disorder) and in 36 healthy control subjects. IFN-gamma was measured using enzyme-linked immunosorbent assay (ELISA). The mean tryptophan breakdown index (kynurenine\\/tryptophan) was significantly higher in the patient group compared with controls (P < 0.05). IFN-gamma measures did not differ between groups (P = 0.23). No relationship was found between measures of psychopathology, symptom severity and activity in the first step in the pathway. A modest correlation was established between the tryptophan breakdown index and illness duration. These results provide evidence for kynurenine pathway upregulation, specifically involving the first enzymatic step, in patients with major psychotic disorder. Increased tryptophan degradation in psychoses may have potential consequences for the treatment of these disorders by informing the development of novel therapeutic compounds.

  13. Further investigation on the radiosynthesis of α-[11C]methyl-tryptophan

    Improved procedures for the radiosynthesis of α-[11C]-methyl-tryptophan and α-[11C]methyl-tryptophan methyl ester were studied. Following α-deprotonation of tryptophan methyl ester benzaldimine with LDA, 60 - 80% of no carrier added [11C]iodomethane was incorporated in 5 minutes at 27 - 30 oC. After HPLC purification, radiochemically pure α-[11C]methyl-tryptophan or its methyl ester was produced with minimum chemical contamination form tryptophan. The [11C]methyl-tryptophan synthesized, however, was found to be a racemate. (Author)

  14. Willpower depletion and framing effects

    de Haan, Thomas; van Veldhuizen, Roel

    2013-01-01

    We investigate whether depleting people's cognitive resources (or willpower) affects the degree to which they are susceptible to framing effects. Recent research in social psychology and economics has suggested that willpower is a resource that can be temporarily depleted and that a depleted level of willpower is associated with self-control problems in a variety of contexts. In this study, we extend the willpower depletion paradigm to framing effects and argue that willpower depletion should...

  15. One-step of tryptophan attenuator inactivation and promoter swapping to improve the production of L-tryptophan in Escherichia coli

    Gu Pengfei

    2012-03-01

    Full Text Available Abstract Background L-tryptophan is an aromatic amino acid widely used in the food, chemical and pharmaceutical industries. In Escherichia coli, L-tryptophan is synthesized from phosphoenolpyruvate and erythrose 4-phosphate by enzymes in the shikimate pathway and L-tryptophan branch pathway, while L-serine and phosphoribosylpyrophosphate are also involved in L-tryptophan synthesis. In order to construct a microbial strain for efficient L-tryptophan production from glucose, we developed a one step tryptophan attenuator inactivation and promoter swapping strategy for metabolic flux optimization after a base strain was obtained by overexpressing the tktA, mutated trpE and aroG genes and inactivating a series of competitive steps. Results The engineered E. coli GPT1002 with tryptophan attenuator inactivation and tryptophan operon promoter substitution exhibited 1.67 ~ 9.29 times higher transcription of tryptophan operon genes than the control GPT1001. In addition, this strain accumulated 1.70 g l-1 L-tryptophan after 36 h batch cultivation in 300-mL shake flask. Bioreactor fermentation experiments showed that GPT1002 could produce 10.15 g l-1 L-tryptophan in 48 h. Conclusions The one step inactivating and promoter swapping is an efficient method for metabolic engineering. This method can also be applied in other bacteria.

  16. Surface geometry of tryptophan adsorbed on gold colloidal nanoparticles

    Hussain, Shafqat; Pang, Yoonsoo

    2015-09-01

    Two distinct surface-enhanced Raman (SER) spectra of tryptophan depending on the surface adsorption geometry were obtained by using colloidal gold nanoparticles reduced by borohydride and citrate ions. According to the vibrational assignments based on DFT simulations, the SER spectra of tryptamine and 3-indolepropionic acid, and the pH dependence of tryptophan SER spectrum, we found that some indole ring vibrations are very sensitive to the surface adsorption geometry of the molecules. With citrate-reduced gold colloids, tryptophan and related molecules mainly adsorb via the protonated amine group while maintaining a perpendicular geometry of the indole ring to the surface. However, a flat geometry of the indole ring to the surface is preferred on the borohydride-reduced gold colloids where the surface adsorption occurs mainly through the indole ring π electrons. By comparing our results with previous reports on the SER spectra of tryptophan on various silver and gold surfaces, we propose a general adsorption model of tryptophan on metal nanosurfaces.

  17. Kinetics of oxidation of tryptophan by sodium hypochlorite

    The oxidation of tryptophan to 3-indoleacetaldehyde with sodium hypochlorite was investigated with 14C labelled DL-tryptophan. The reaction was performed under pseudo first order conditions. From the pH dependence of the reaction it was concluded that only the unprotonated tryptophan is converted to the aldehyde. The activation energy is 35 +- 2.2 (SE) kJ x mol-1 as derived from the Arrhenius plot. Variing the pH between 8.5 and 11.0 and the temperature in the range from 298 K to 318 K did not alter the selectivity of the reaction as confirmed by TLC of the product (purity >= 90%). A possible reaction mechanism is proposed. (orig.)

  18. Depletion of intense fields

    Seipt, D; Marklund, M; Bulanov, S S

    2016-01-01

    The interaction of charged particles and photons with intense electromagnetic fields gives rise to multi-photon Compton and Breit-Wheeler processes. These are usually described in the framework of the external field approximation, where the electromagnetic field is assumed to have infinite energy. However, the multi-photon nature of these processes implies the absorption of a significant number of photons, which scales as the external field amplitude cubed. As a result, the interaction of a highly charged electron bunch with an intense laser pulse can lead to significant depletion of the laser pulse energy, thus rendering the external field approximation invalid. We provide relevant estimates for this depletion and find it to become important in the interaction between fields of amplitude $a_0 \\sim 10^3$ and electron bunches with charges of the order of nC.

  19. Intrinsic Depletion or Not

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

    in between he polymer cushion and bulk water the layer was attributed to water of reduced density and was called "depletion layer".  Impurities or preparative artefacts were excluded as its origin. Later on, the formation of nanobubbles from this vapour-like water phase was initiated by tipping the......  The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...... carrier and biomimetic membranes deposited thereupon and exposed to bulk water. While monitoring the sequential build-up of the sandwiched composite structure by continuous neutron reflectivity experiments the formation of an unexpected additional layer was detected (1). Located at the polystyrene surface...

  20. Ozone depletion by hydrofluorocarbons

    Hurwitz, Margaret M.; Fleming, Eric L.; Newman, Paul A.; Li, Feng; Mlawer, Eli; Cady-Pereira, Karen; Bailey, Roshelle

    2015-10-01

    Atmospheric concentrations of hydrofluorocarbons (HFCs) are projected to increase considerably in the coming decades. Chemistry climate model simulations forced by current projections show that HFCs will impact the global atmosphere increasingly through 2050. As strong radiative forcers, HFCs increase tropospheric and stratospheric temperatures, thereby enhancing ozone-destroying catalytic cycles and modifying the atmospheric circulation. These changes lead to a weak depletion of stratospheric ozone. Simulations with the NASA Goddard Space Flight Center 2-D model show that HFC-125 is the most important contributor to HFC-related atmospheric change in 2050; its effects are comparable to the combined impacts of HFC-23, HFC-32, HFC-134a, and HFC-143a. Incorporating the interactions between chemistry, radiation, and dynamics, ozone depletion potentials (ODPs) for HFCs range from 0.39 × 10-3 to 30.0 × 10-3, approximately 100 times larger than previous ODP estimates which were based solely on chemical effects.

  1. Phasor approaches simplify the analysis of tryptophan fluorescence data in protein denaturation studies

    Bader, A.N.; Visser, N.V.; Amerongen, van H.; Visser, A.J.W.G.

    2014-01-01

    The intrinsic fluorescence of tryptophan is frequently used to investigate the structure of proteins. The analysis of tryptophan fluorescence data is challenging: fluorescence (anisotropy) decays typically have multiple lifetime (correlation time) components and fluorescence spectra are broad and ex

  2. Tryptophan Hydroxylase 2 Gene Polymorphism in Anxiety and Depressive Disorder in Kashmiri Population

    Mushtaq, Raheel; Shoib, Sheikh; Shah, Tabindah; Mushtaq, Sahil

    2014-01-01

    Background: The gene of tryptophan hydroxylase is widely recognized as a major candidate gene in many psychiatric disorders. However, no study has been done which investigates tryptophan hydroxylase 2 gene polymorphism in anxiety and depressive disorders in Kashmiri population (India).

  3. Incorporation of tryptophan analogues into the lantibiotic nisin.

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin. PMID:26872656

  4. Capital expenditure and depletion

    In the future, the increase in oil demand will be covered for the most part by non conventional oils, but conventional sources will continue to represent a preponderant share of the world oil supply. Their depletion represents a complex challenge involving technological, economic and political factors. At the same time, there is reason for concern about the decrease in exploration budgets at the major oil companies. (author)

  5. Alleviation of hysteria in laying hens with dietary tryptophan.

    Laycock, S. R.; Ball, R O

    1990-01-01

    A commercial layer breeder flock that was suffering from hysteria was fed a diet containing 5 grams tryptophan/kg for six days. The incidence of episodes of hysteria declined from five times/hour on day 0 to once/hour on day 6 and none on day 8. Feed consumption increased from 107 g to 145 g/hen/day and egg production increased 23% during the six day feeding period. The tryptophan concentration in plasma doubled (from 95.6 to 188.2 mumol/mL). Plasma phenylalanine and tyrosine also increased. ...

  6. Maintenance valine, isoleucine, and tryptophan requirements for poultry.

    de Lima, M B; Sakomura, N K; Dorigam, J C P; da Silva, E P; Ferreira, N T; Fernandes, J B K

    2016-04-01

    Poultry maintenance requirements for valine, isoleucine, and tryptophan were measured by nitrogen balance using different unit systems. The nitrogen balance trial lasted 5 d with 48 h of fasting (with roosters receiving only water+sucrose) and the last 72 h for feeding and excreta collection. Forty grams of each diet first-limiting in valine, isoleucine, or tryptophan was fed by tube each day (3 d) to give a range of intakes from 0 to 101, 0 to 119, and 0 to 34 mg/kg BW d of valine, isoleucine, and tryptophan, respectively. A nitrogen-free diet containing energy, vitamins, and minerals, meeting the rooster requirements, was offered ad libitum during these three d. To confirm that the amino acids studied were limiting, a treatment was added with a control diet formulated by adding 0.24 g/kg of L-valine, 0.21 g/kg of L-isoleucine, and 0.10 g/kg of L-tryptophan to the diets with lower amino acid level. Excreta were collected during the last 3 d of the balance period and the nitrogen content of the excreta was analyzed. For each amino acid, a linear regression between nitrogen retention (NR) and amino acid intake was performed. The equations from linear regression were: NR=-98.6 (±10.1)+2.4 (±0.2)×Val, NR=-46.9 (±7.1)+2.3 (±0.1)×Ile, NR=-39.5 (±7.7)+7.3 (±0.4)×Trp; where Val, Ile, and Trp are the intakes of valine, isoleucine, and tryptophan in mg/kg body weight per d, respectively. The valine, isoleucine, and tryptophan required to maintain the body at zero NR were calculated to be 41, 20, and 5 mg/kg body weight per d, respectively. For the system unit mg per kg of metabolic weight, the intake of valine, isoleucine, and tryptophan was 59, 32, and 9, respectively. Considering the degree of maturity of the animal and body protein content (BPm (0.73)×u), the amounts of valine, isoleucine, and tryptophan required for maintenance were calculated to be 247, 134, and 37 mg per unit of maintenance protein (BPm (0.73)×u) per d. Maintenance requirement is more

  7. Dynamic behavior in mathematical models of the tryptophan operon

    Santillán, Moisés; Mackey, Michael C.

    2001-03-01

    This paper surveys the general theory of operon regulation as first formulated by Goodwin and Griffith, and then goes on to consider in detail models of regulation of tryptophan production by Bliss, Sinha, and Santillán and Mackey, and the interrelationships between them. We further give a linear stability analysis of the Santillán and Mackey model for wild type E. coli as well as three different mutant strains that have been previously studied in the literature. This stability analysis indicates that the tryptophan production systems should be stable, which is in accord with our numerical results.

  8. Subtle stereoconformational change of tryptophanase provoking D-tryptophan activity

    It has been found in this investigation that the stereospecificity of enzyme is full of flexibility and that tryptophanase has an activity also toward D-tryptophan in ammonium phosphate solution at high concentration as L-tryptophan. This fact may show that D-amino acids have physiologically significant activity. It is considered that the appearance of such the activity is related to a stereoconformational change of tryptophanase. This was investigated by the measurement of circular dichroism and fluorescence spectra. Furthermore the change of steric structure was also examined on the denaturated tryptophanase inactivated by gamma irradiation. (M.H.)

  9. Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester.

    Jonas, A J; Butler, I J

    1989-01-01

    Tryptophan ethyl ester, a lipid-soluble tryptophan derivative, was used to bypass defective gastrointestinal neutral amino acid transport in a child with Hartnup disease. The child's baseline tryptophan concentrations in serum (20 +/- 6 microM) and cerebrospinal fluid (1.0 +/- 0.2 microM) were persistently less than 50% of normal values. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, was also less than 50% of normal (21 +/- 2 ng/ml). Serum tryptophan concentr...

  10. Enhancement of rat brain metabolism of a tryptophan load by chronic ethanol administration

    1980-01-01

    We have previously shown that chronic ethanol administration enhances brain 5-hydroxytryptamine synthesis by increasing the availability of circulating tryptophan to the brain secondary to the decreased liver tryptophan pyrrolase activity. We now find that ethanol enhances the brain metabolism of a tryptophan load by the same mechanism. The results are discussed in relation to ethanol preference and the need for further clinical work on the effects of alcoholism on tryptophan metabolism.

  11. Ozone-depleting Substances (ODS)

    U.S. Environmental Protection Agency — This site includes all of the ozone-depleting substances (ODS) recognized by the Montreal Protocol. The data include ozone depletion potentials (ODP), global...

  12. Linear mapping of tryptophan residues in Vesiculovirus M and N proteins by partial chemical cleavage.

    Brown, E.; Prevec, L.

    1982-01-01

    Nonlimit chemical cleavage at tryptophan residues of protein labeled at the amino terminus afforded a simple procedure for generating specific fragments and for mapping tryptophan positions. A comparison of the matrix (M) and nucleocapsid (N) proteins of four members of the Vesiculovirus group by this procedure suggests considerable conservation of tryptophan number and location in the four serotypes examined.

  13. Depleted uranium management alternatives

    This report evaluates two management alternatives for Department of Energy depleted uranium: continued storage as uranium hexafluoride, and conversion to uranium metal and fabrication to shielding for spent nuclear fuel containers. The results will be used to compare the costs with other alternatives, such as disposal. Cost estimates for the continued storage alternative are based on a life-cycle of 27 years through the year 2020. Cost estimates for the recycle alternative are based on existing conversion process costs and Capital costs for fabricating the containers. Additionally, the recycle alternative accounts for costs associated with intermediate product resale and secondary waste disposal for materials generated during the conversion process

  14. Stratospheric ozone depletion

    The amount of stratospheric ozone and the reduction of the ozone layer vary according to seasons and latitudes. At present total and vertical ozone is monitored over all Austria. The mean monthly ozone levels between 1994 and 2000 are presented. Data on stratospheric ozone and UV-B radiation are published daily on the home page http: www.lebesministerium.at. The use of ozone depleting substances such as chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs) is provided. Besides, the national measures taken to reduce their use. Figs. 2, Tables 2. (nevyjel)

  15. Tryptophan as a link between psychopathology and somatic states

    Russo, Sascha; Kema, Ido P; Fokkema, M Rebecca; Boon, Jim C; Willemse, Pax H B; de Vries, Elisabeth G E; den Boer, Johannes A; Korf, Jakob

    2003-01-01

    OBJECTIVE: Several somatic illnesses are associated with psychiatric comorbidity. Evidence is provided that availability of the essential amino acid tryptophan, which is the precursor of serotonin, may cause this phenomenon. METHODS: We performed a database search to find relevant articles published

  16. Electron-transfer reactions of tryptophan and tyrosine derivatives

    Oxidation of tryptophan, tyrosine, and derivatives by oxidizing radicals was studied by pulse radiolysis in aqueous solutions at 20 0C. Rate constants for the oxidation of tryptophan derivatives with .N3 and Br2-. radicals vary from 8 x 108 to 4.8 and 109 M-1 s-1 and oxidation goes to completion; no pH dependence was observed. Oxidation rate constants for tyrosine derivatives increase upon deprotonation of the phenolic residue at higher pH. Redox potentials for the indolyl and phenoxyl radicals were derived from the measured equilibrium constants by using p-methoxyphenol (E/sub 7.5/ = 0.6 and E13 = 0.4 V), bisulfite (E3 = 0.84 V), and guanosine (E7 = 0.91 V) redox couples as reference systems. Redox potentials of tryptophan derivatives were found to be in dependent on the nature of the side chain and higher than the redox potentials of tryptophan derivatives. Electron transfer from tyrosine to tryptophyl radical was found to be slow in neutral media and is suggested to proceed via multiple steps, one of which is proton transfer from tyrosine to tryptophyl radical followed by electron transfer. 26 references, 2 figures, 4 tables

  17. Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

    Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

    2010-01-01

    The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

  18. Decomposition of protein tryptophan fluorescence spectra into log-normal components. III. Correlation between fluorescence and microenvironment parameters of individual tryptophan residues.

    Reshetnyak, Y K; Koshevnik, Y; Burstein, E A

    2001-01-01

    In our previous paper (Reshetnyak, Ya. K., and E. A. Burstein. 2001. Biophys. J. 81:1710-1734) we confirmed the existence of five statistically discrete classes of emitting tryptophan fluorophores in proteins. The differences in fluorescence properties of tryptophan residues of these five classes reflect differences in interactions of excited states of tryptophan fluorophores with their microenvironment in proteins. Here we present a system of describing physical and structural parameters of ...

  19. Comparison of fractal dimension and Shannon entropy in myocytes from rats treated with histidine-tryptophan-glutamate and histidine-tryptophan cetoglutarate

    de Oliveira, Marcos Aurélio Barboza; Brandi, Antônio Carlos; dos Santos, Carlos Alberto; Botelho, Paulo Henrique Husseni; Cortez, José Luís Lasso; de Godoy, Moacir Fernandes; Braile, Domingo Marcolino

    2014-01-01

    Introduction Solutions that cause elective cardiac arrest are constantly evolving, but the ideal compound has not yet been found. The authors compare a new cardioplegic solution with histidine-tryptophan-glutamate (Group 2) and other one with histidine-tryptophan-cetoglutarate (Group 1) in a model of isolated rat heart. Objective To quantify the fractal dimension and Shannon entropy in rat myocytes subjected to cardioplegia solution using histidine-tryptophan with glutamate in an experimental...

  20. Pre-Transplant Donor-Specific T-Cell Alloreactivity Is Strongly Associated with Early Acute Cellular Rejection in Kidney Transplant Recipients Not Receiving T-Cell Depleting Induction Therapy

    Crespo, Elena; Lucia, Marc; Cruzado, Josep M.; Luque, Sergio; Melilli, Edoardo; Manonelles, Anna; Lloberas, Nuria; Torras, Joan; Grinyó, Josep M.; Bestard, Oriol

    2015-01-01

    Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, p...

  1. The stimulus-induced release of 5-hydroxytryptamine and tryptophan from superfused rat brain synaptosomes

    The synthesis of 5-hydroxytryptamine (5-HT) from 3H-tryptophan in rat forebrain synaptosomes was studied. Synaptosomes which had been preincubated with 3H-tryptophan were perfused with Krebs solution and the release of tryptophan, 5-HT and 5-hydroxyindoleactic acid (5-HIAA) was determined. K+ depolarization induced a Ca2+ -dependent release of 5-HT and tryptophan but had no effect on 5-HIAA efflux. This finding suggests that the release of tryptophan is unlikely to be a non-specific effect of depolarization. (Author)

  2. L-Tryptophan prevents Escherichia coli biofilm formation and triggers biofilm degradation.

    Shimazaki, Junji; Furukawa, Soichi; Ogihara, Hirokazu; Morinaga, Yasushi

    2012-03-23

    The effect of deletion of trp operon and tna operon on the Escherichia coli biofilm formation was investigated in order to elucidate the role of L-tryptophan metabolism in biofilm formation. trp operon deletion mutants ΔtrpC, ΔtrpD and ΔtrpE deficient in L-tryptophan biosynthesis showed higher biofilm formation. In addition, ΔtnaC with increased L-tryptophan degradation activity showed higher biofilm formation. On the contrary, ΔtnaA deletion mutant which lost L-tryptophan degradation activity showed low biofilm formation. From these results, it was suggested that decrease of intracellular L-tryptophan level induced biofilm formation and increase of L-tryptophan repressed biofilm formation. So the effect of the addition of L-tryptophan to the medium on the E. coli biofilm formation was investigated. L-Tryptophan addition at starting culture decreased biofilm formation and furthermore L-tryptophan addition after 16 h culture induced the degradation of preformed biofilm. From the above results, it was suggested that maintenance of high intracellular L-tryptophan concentration prevents E. coli biofilm formation and elevation of intracellular L-tryptophan concentration triggers degradation of matured biofilm. PMID:22386992

  3. Depleted uranium: Metabolic disruptor?

    The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolizing vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions. (authors)

  4. Riddle of depleted uranium

    Depleted Uranium (DU) is the waste product of uranium enrichment from the manufacturing of fuel rods for nuclear reactors in nuclear power plants and nuclear power ships. DU may also results from the reprocessing of spent nuclear reactor fuel. Potentially DU has both chemical and radiological toxicity with two important targets organs being the kidney and the lungs. DU is made into a metal and, due to its availability, low price, high specific weight, density and melting point as well as its pyrophoricity; it has a wide range of civilian and military applications. Due to the use of DU over the recent years, there appeared in some press on health hazards that are alleged to be due to DU. In these paper properties, applications, potential environmental and health effects of DU are briefly reviewed

  5. Depleted zinc: Properties, application, production

    The addition of ZnO, depleted in the Zn-64 isotope, to the water of boiling water nuclear reactors lessens the accumulation of Co-60 on the reactor interior surfaces, reduces radioactive wastes and increases the reactor service-life because of the inhibitory action of zinc on inter-granular stress corrosion cracking. To the same effect depleted zinc in the form of acetate dihydrate is used in pressurized water reactors. Gas centrifuge isotope separation method is applied for production of depleted zinc on the industrial scale. More than 20 years of depleted zinc application history demonstrates its benefits for reduction of NPP personnel radiation exposure and combating construction materials corrosion.

  6. Elementary processes during collisions of ions with tryptophan molecules

    Afrosimov, V. V.; Basalaev, A. A.; Kuz'michev, V. V.; Panov, M. N.; Smirnov, O. V.

    2016-03-01

    The relative cross sections of elementary processes occurring in single collisions of tryptophan molecules in the gaseous phase with He2+ ions with energy 4 keV/u are measured using time-of-flight mass spectrometry for studying the mechanism of radiation damage of amino acid molecules. The fragmentation channels for intermediate singly and doubly charged tryptophan molecular ions formed during one-electron capture, two-electron capture, and electron capture with ionization are investigated. Significant difference is observed in the mass spectra of fragmentation of intermediate doubly charged ions formed during the capture with ionization and double capture, which is associated with different energies of excitation of {C11H12N2O2}2+* ions.

  7. Investigation of Fragmentation of Tryptophan Nitrogen Radical Cation

    Piatkivskyi, Andrii; Happ, Marshall; Lau, Justin Kai-Chi; Siu, K. W. Michael; Hopkinson, Alan C.; Ryzhov, Victor

    2015-08-01

    This work describes investigation of the fragmentation mechanism of tryptophan N-indolyl radical cation, H3N+-TrpN• ( m/ z 204) studied via DFT calculations and several gas-phase experimental techniques. The main fragment ion at m/ z 131, shown to be a mixture of up to four isomers including 3-methylindole (3MI) π-radical cation, was found to undergo further loss of an H atom to yield one of the two isomeric m/ z 130 ions. 3-Methylindole radical cation generated independently (via CID of [CuII(terpy)3MI]•2+) displayed gas-phase reactivity partially similar to that of the m/ z 131 fragment, further confirming our proposed mechanism. CID of deuterated tryptophan N-indolyl radical cation ( m/ z 208) suggested that up to six H atoms are involved in the pathway to formation of the m/ z 131 ion, consistent with hydrogen atom scrambling during CID of protonated Trp.

  8. Aromatic amine dehydrogenase, a second tryptophan tryptophylquinone enzyme.

    Govindaraj, S; Eisenstein, E.; Jones, L. H.; Sanders-Loehr, J; Chistoserdov, A Y; Davidson, V L; Edwards, S. L.

    1994-01-01

    Aromatic amine dehydrogenase (AADH) catalyzes the oxidative deamination of aromatic amines including tyramine and dopamine. AADH is structurally similar to methylamine dehydrogenase (MADH) and possesses the same tryptophan tryptophylquinone (TTQ) prosthetic group. AADH exhibits an alpha 2 beta 2 structure with subunit molecular weights of 39,000 and 18,000 and with a quinone covalently attached to each beta subunit. Neither subunit cross-reacted immunologically with antibodies to the correspo...

  9. Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans

    Lionella Palego; Laura Betti; Alessandra Rossi; Gino Giannaccini

    2016-01-01

    L-Tryptophan is the unique protein amino acid (AA) bearing an indole ring: its biotransformation in living organisms contributes either to keeping this chemical group in cells and tissues or to breaking it, by generating in both cases a variety of bioactive molecules. Investigations on the biology of Trp highlight the pleiotropic effects of its small derivatives on homeostasis processes. In addition to protein turn-over, in humans the pathways of Trp indole derivatives cover the synthesis of ...

  10. Tryptophan-abhängige Pigmentsynthese bei Brandpilzen

    Mayer, Peter Karl

    2007-01-01

    Im Jahre 1998 konnten MAYSER ET AL. erstmals nachweisen, dass die Aminosäure L-Tryptophan bei dem Brandpilz Malassezia furfur eine Pigmentbildung induziert. Die entstandenen Pigmente und Fluorochrome werden mit dem Krankheitsbild der Pityriasis versicolor in Verbindung gebracht. Im Gegensatz zu Malassezia furfur sind Brandpilze obligate Pflanzenparasiten. Aufgrund der phylogenetischen Klassifikation von Malassezia furfur als Brandpilz wurden insgesamt 27 Brandpilze auf Pigmentbildung untersuc...

  11. Structural Insights into Regioselectivity in the Enzymatic Chlorination of Tryptophan

    Zhu, Xiaofeng; De Laurentis, Walter; Leang, Khim; Herrmann, Julia; Ihlefeld, Katja; van Pée, Karl-Heinz; Naismith, James H.

    2009-01-01

    The regioselectively controlled introduction of chlorine into organic molecules is an important biological and chemical process. This importance derives from the observation that many pharmaceutically active natural products contain a chlorine atom. Flavin-dependent halogenases are one of the principal enzyme families responsible for regioselective halogenation of natural products. Structural studies of two flavin-dependent tryptophan 7-halogenases (PrnA and RebH) have generated important ins...

  12. Tryptophan-Containing Cyclic Dipeptides Studied by Optical Activity

    Hudecová, Jana; Horníček, Jan; Šebestík, Jaroslav; Buděšínský, Miloš; Bouř, Petr

    Oxford : Diamond, 2011. s. 20-20. [CD 2011. The International Conference on Chiroptical Spectroscopy /13./. 24.07.2011-28.07.2011, Oxford] R&D Projects: GA MŠk(CZ) LH11033; GA ČR GAP208/11/0105 Grant ostatní: AV ČR(CZ) M200550902; UK CZ(CZ) 126310 Institutional research plan: CEZ:AV0Z40550506 Keywords : cyclic dipeptides * ROA * DFT calculations * tryptophan e Subject RIV: CF - Physical ; Theoretical Chemistry

  13. Immunochemical characterization of brain and pineal tryptophan hydroxylase.

    Chung, Y. I.; Park, D. H.; Kim, M.; Baker, H; Joh, T H

    2001-01-01

    Recombinant mouse tryptophan hydroxylase (TPH) was expressed in Escherichia coli, using a bacterial expression vector and has been purified to homogeneity by sonication followed by Sepharose 4B column chromatography and native slab gel electrophoresis. This purified enzymatically active TPH protein was used for production of a specific antiserum. This antiserum identified the predicted TPH band (molecular weight, 54 kDa) on Western blot of crude extracts from the rat and mouse dorsal raphe, a...

  14. Separation of tryptophan enantiomers with molecularly imprinted polypyrrole electrode column

    2010-01-01

    In this study,we have fabricated molecularly imprinted polypyrrole(PPy) packed electrode columns and investigated their effects on separation of tryptophan(Trp) enantiomers by using potential control.The results indicate that the imprinted PPy electrode columns could efficiently enhance the L-Trp uptake and separate Trp enantiomers effectively,implying the great potential for the enantioselective recognition of other amino acids enantiomers.

  15. Regulation of Tryptophan Operon Expression in the Archaeon Methanothermobacter thermautotrophicus

    Xie, Yunwei; Reeve, John N.

    2005-01-01

    Conserved trp genes encode enzymes that catalyze tryptophan biosynthesis in all three biological domains, and studies of their expression in Bacteria and eukaryotes have revealed a variety of different regulatory mechanisms. The results reported here provide the first detailed description of an archaeal trp gene regulatory system. We have established that the trpEGCFBAD operon in Methanothermobacter thermautotrophicus is transcribed divergently from a gene (designated trpY) that encodes a try...

  16. Gramicidin tryptophans mediate formamidinium-induced channel stabilization.

    Seoh, S A; Busath, D

    1995-01-01

    Compared with alkali metal cations, formamidinium ions stabilize the gramicidin A channel molecule in monoolein bilayers (Seoh and Busath, 1993a). A similar effect is observed with N-acetyl gramicidin channel molecules in spite of the modified forces at the dimeric junction (Seoh and Busath, 1993b). Here we use electrophysiological measurements with tryptophan-to-phenylalanine-substituted gramicidin analogs to show that the formamidinium-induced channel molecule stabilization is eliminated wh...

  17. Crystal Structure and Mechanism of Tryptophan 2,3-Dioxygenase, a Heme Enzyme Involved in Tryptophan Catabolism and in Quinolinate Biosynthesis

    Zhang,Y.; Kang, S.; Mukherjee, T.; Bale, S.; Crane, B.; Begley, T.; Ealick, S.

    2007-01-01

    The structure of tryptophan 2,3-dioxygenase (TDO) from Ralstonia metallidurans was determined at 2.4 {angstrom}. TDO catalyzes the irreversible oxidation of L-tryptophan to N-formyl kynurenine, which is the initial step in tryptophan catabolism. TDO is a heme-containing enzyme and is highly specific for its substrate L-tryptophan. The structure is a tetramer with a heme cofactor bound at each active site. The monomeric fold, as well as the heme binding site, is similar to that of the large domain of indoleamine 2,3-dioxygenase, an enzyme that catalyzes the same reaction except with a broader substrate tolerance. Modeling of the putative (S)-tryptophan hydroperoxide intermediate into the active site, as well as substrate analogue and mutagenesis studies, are consistent with a Criegee mechanism for the reaction.

  18. Tryptophan synthase of Phaeophyceae originated from the secondary host nucleus

    ZHANG Yalan; CHI Shan; WU Shuangxiu; LIU Cui; YU Jun; WANG Xumin; CHEN Shengping; LIU Tao

    2014-01-01

    Tryptophan synthase (TS, EC 4.2.1.20) catalyzes the last two steps of L-tryptophan biosynthesis. In pro-karyotes, tryptophan synthase is a multi-enzyme complex, and it consists ofαandβsubunit which forms anα-ββ-αcomplex. In fungi and diatoms, TS is a bifunctional enzyme. Because of the limited genomic and transcriptomic data of algae, there are few studies on TS evolution of algae. Here we analyzed the data of the 1000 Plants Project (1KP), and focused on red algae and brown algae. We found out that the TS of Phaeophy-ceae were fusion genes, which probably originated from the secondary host nucleus, and that the TS of Rho-dophyta contained two genes, TSA and TSB, which both display a possible cyanobacterial origin at the time of primary endosymbiosis. In addition, there were two types of TSB genes (TSB1 and TSB2). Through the multiple sequence alignment of TSB proteins, we found several residues conserved in TSB1 but variable in TSB2 which connect withαsubunit. The phenomenon may suggest that the TSB2 sequences of Rhodophyta cannot form stable complex with TSA.

  19. Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

    Ravikumar A

    2000-07-01

    Full Text Available Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport in the plasma of these patients. Concentration of digoxin, a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.

  20. L-Tryptophan L-tryptophanium bromide: Anhydrous and monohydrate

    Ghazaryan, V. V.; Giester, G.; Fleck, M.; Petrosyan, A. M.

    2015-12-01

    L-Tryptophan L-tryptophanium bromide (I) and L-tryptophan L-tryptophanium bromide monohydrate (II) are new salts with (A⋯A+) type dimeric cation. The salt (I) crystallizes in the monoclinic system (space group P21, Z = 2) and is isostructural with respective chloride (V.V. Ghazaryan et al., Spectrochim. Acta A 136(2015) 743-750), while the salt (II) was obtained previously (T. Takigawa et al., Bull. Chem. Soc. Jap. 39(1966) 2369-2378) and described as hemyhydrate without structure determination. The salt (II) crystallizes in orthorhombic system (space group P212121, Z = 4). The dimeric cations in (I) and (II) are formed by O-H⋯O hydrogen bonds with the O⋯O distances equal to 2.538(3) Å and 2.481(3) Å respectively. The infrared and Raman spectra of the crystals are studied and compared with the spectra of L-tryptophan L-tryptophanium chloride and L-tryptophanium bromide.

  1. Depletable resources and the economy.

    Heijman, W.J.M.

    1991-01-01

    The subject of this thesis is the depletion of scarce resources. The main question to be answered is how to avoid future resource crises. After dealing with the complex relation between nature and economics, three important concepts in relation with resource depletion are discussed: steady state, ti

  2. Stratospheric ozone depletion.

    Rowland, F Sherwood

    2006-05-29

    Solar ultraviolet radiation creates an ozone layer in the atmosphere which in turn completely absorbs the most energetic fraction of this radiation. This process both warms the air, creating the stratosphere between 15 and 50 km altitude, and protects the biological activities at the Earth's surface from this damaging radiation. In the last half-century, the chemical mechanisms operating within the ozone layer have been shown to include very efficient catalytic chain reactions involving the chemical species HO, HO2, NO, NO2, Cl and ClO. The NOX and ClOX chains involve the emission at Earth's surface of stable molecules in very low concentration (N2O, CCl2F2, CCl3F, etc.) which wander in the atmosphere for as long as a century before absorbing ultraviolet radiation and decomposing to create NO and Cl in the middle of the stratospheric ozone layer. The growing emissions of synthetic chlorofluorocarbon molecules cause a significant diminution in the ozone content of the stratosphere, with the result that more solar ultraviolet-B radiation (290-320 nm wavelength) reaches the surface. This ozone loss occurs in the temperate zone latitudes in all seasons, and especially drastically since the early 1980s in the south polar springtime-the 'Antarctic ozone hole'. The chemical reactions causing this ozone depletion are primarily based on atomic Cl and ClO, the product of its reaction with ozone. The further manufacture of chlorofluorocarbons has been banned by the 1992 revisions of the 1987 Montreal Protocol of the United Nations. Atmospheric measurements have confirmed that the Protocol has been very successful in reducing further emissions of these molecules. Recovery of the stratosphere to the ozone conditions of the 1950s will occur slowly over the rest of the twenty-first century because of the long lifetime of the precursor molecules. PMID:16627294

  3. Adenosine triphosphate-pyrophosphate isotopic exchange reaction: a tool for determination of tryptophan

    Quantitative determination of tryptophan at the picomole level is described, using the ATP-[32P]PPi isotopic exchange reaction catalyzed by tryptophanyl-tRNA synthetase. Sensitivity limits of 500 fmol were obtained. The presence of other amino acids at a 1000-fold excess over tryptophan did not interfere significantly with the quantitative determination of tryptophan. The specificity of the reaction was checked using five tryptophan analogs. These analogs did not prevent the determination of tryptophan when present in the same concentration range as tryptophan. When sensitive determination of a single amino acid is needed, the ATP-[32P]PPi exchange reaction catalyzed by aminoacyl-tRNA synthetases is suggested as a general method and as an alternative to HPLC procedures

  4. Cane molasses as a source of precursors in the bioproduction of tryptophan by Bacillus subtilis

    Marzieh Dehghan Shasaltaneh; Zahra Moosavi-Nejad; Sara Gharavi; Jamshid Fooladi

    2013-01-01

    Background and Objectives The essential amino acid L-tryptophan can be produced by a condensation reaction between indole and L-serine, catalyzed by B. subtilis with tryptophan synthase activity. Application of the tryptophan is widespread in the biotechnology domain and is sometimes added to feed products as a food fortifier. Materials and Methods The optimum concentration of the Iranian cane molasses was determined by measuring the amount of biomass after growth in 1 to 30 g/mL of molasses....

  5. Proton transfer in histidine-tryptophan heterodimers embedded in helium droplets

    We used cold helium droplets as nano-scale reactors to form and ionize, by electron bombardment and charge transfer, aromatic amino acid heterodimers of histidine with tryptophan, methyl-tryptophan, and indole. The molecular interaction occurring through an N–H ⋅ ⋅ ⋅ N hydrogen bond leads to a proton transfer from the indole group of tryptophan to the imidazole group of histidine in a radical cationic environment

  6. Tryptophan fluorescence quenching by alkaline earth metal cations in deionized bacteriorhodopsin.

    Wang, G; Wang, A J; Hu, K S

    2000-12-01

    Tryptophan quenching by the addition of alkaline earth metal cations to deionized bacteriorhodopsin suspensions was determined. The results show that the addition of cation primarily quenches fluorescence from surface tryptophan residues. The quenched intensity exhibits a 1/R dependence, where R is the ionic radius of the corresponding metal ion. This observation results from a stronger energy transfer coupling between the tryptophan and the retinal. The membrane curvature may be involved as a result of cations motion and correlated conformational changes. PMID:11332888

  7. Physiological studies of tryptophan transport and tryptophanase operon induction in Escherichia coli.

    Yanofsky, C; Horn, V.; Gollnick, P

    1991-01-01

    Escherichia coli forms three permeases that can transport the amino acid tryptophan: Mtr, AroP, and TnaB. The structural genes for these permeases reside in separate operons that are subject to different mechanisms of regulation. We have exploited the fact that the tryptophanase (tna) operon is induced by tryptophan to infer how tryptophan transport is influenced by the growth medium and by mutations that inactivate each of the permease proteins. In an acid-hydrolyzed casein medium, high leve...

  8. Studies on the mechanism by which tryptophan efflux from isolated synaptosomes is stimulated by depolarization.

    Collard, K. J.; Wilkinson, L S; Lewis, D J

    1988-01-01

    1. The efflux and influx of tryptophan across the synaptosomal plasma membrane has been studied under a variety of experimental conditions, in order to examine the mechanism by which depolarization enhances the efflux of tryptophan from superfused synaptosomes. 2. Efflux of [3H]-tryptophan from preloaded superfused synaptosomes was found to be enhanced by K+ depolarization in a Ca2+ and dose-dependent manner. In contrast, [3H]-phenylalanine efflux was only poorly stimulated by depolarization ...

  9. Arabidopsis cytochrome P450 cyp83B1 mutations activate the tryptophan biosynthetic pathway.

    Smolen, Gromoslaw; Bender, Judith

    2002-01-01

    In plants, the tryptophan biosynthetic pathway provides a number of important secondary metabolites including the growth regulator indole-3-acetic acid (IAA) and indole glucosinolate defense compounds. Genes encoding tryptophan pathway enzymes are transcriptionally induced by a variety of stress signals, presumably to increase the production of both tryptophan and secondary metabolites during defense responses. To understand the mechanism of transcriptional induction, we isolated altered tryp...

  10. Radiolysis of aqueous oxygen-free solutions of tryptophan at various pH values

    Gamma radiolysis of 10 sup(-2)M aqueous oxygen-free tryptophan solutions irradiated at various pH values and in a Nsub(2)O atmosphere was investigated. The values of the radiation losses of tryptophan and the yields of NHsub(3) were determined. Using HPLC with an electrochemical detector, the formation of hydroxylated radiation products of tryptophan was followed. The effect of pH on the radiolysis course is discussed. (author)

  11. Decreased tryptophan and increased kynurenine levels in mastocytosis associated with digestive symptoms.

    Georgin-Lavialle, Sophie; Launay, Jean-Marie; Côté, Francine; Soucié, Erinn; Soria, Angèle; Damaj, Gandhi; Moura, Daniela Silva; Canioni, Danielle; Hanssens, Katia; Chandesris, Marie-Olivia; Barète, Stéphane; Dubreuil, Patrice; Lortholary, Olivier; Hermine, Olivier; Sokol, Harry

    2016-01-01

    The main metabolism pathway of tryptophan is protein formation, but it can also be metabolized into serotonin and kynurenine. Indoleamine 2,3-dioxygenase (IDO) is the enzyme that catalyzes the degradation of tryptophan into kynurenine. Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in various tissues with 57% of patients having gastrointestinal involvement. We studied tryptophan metabolism in mastocytosis patients displaying or not gastrointestinal features an...

  12. Proton transfer in histidine-tryptophan heterodimers embedded in helium droplets

    Bellina, Bruno; Merthe, Daniel J.; Kresin, Vitaly V. [Department of Physics and Astronomy, University of Southern California, Los Angeles, California 90089-0484 (United States)

    2015-03-21

    We used cold helium droplets as nano-scale reactors to form and ionize, by electron bombardment and charge transfer, aromatic amino acid heterodimers of histidine with tryptophan, methyl-tryptophan, and indole. The molecular interaction occurring through an N–H ⋅ ⋅ ⋅ N hydrogen bond leads to a proton transfer from the indole group of tryptophan to the imidazole group of histidine in a radical cationic environment.

  13. Proton transfer in histidine-tryptophan heterodimers embedded in helium droplets

    Bellina, Bruno; Kresin, Vitaly V

    2015-01-01

    We used cold helium droplets as nano-scale reactors to form and ionize, by electron bombardment and charge transfer, aromatic amino acid heterodimers of histidine with tryptophan, methyl-tryptophan, and indole. The molecular interaction occurring through an N-H...N hydrogen bond leads to a proton transfer from the indole group of tryptophan to the imidazole group of histidine in a radical cationic environment.

  14. Proton transfer in histidine-tryptophan heterodimers embedded in helium droplets

    Bellina, Bruno; Merthe, Daniel J.; Kresin, Vitaly V.

    2015-03-01

    We used cold helium droplets as nano-scale reactors to form and ionize, by electron bombardment and charge transfer, aromatic amino acid heterodimers of histidine with tryptophan, methyl-tryptophan, and indole. The molecular interaction occurring through an N-H ṡ ṡ ṡ N hydrogen bond leads to a proton transfer from the indole group of tryptophan to the imidazole group of histidine in a radical cationic environment.

  15. Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester.

    Jonas, A J; Butler, I J

    1989-07-01

    Tryptophan ethyl ester, a lipid-soluble tryptophan derivative, was used to bypass defective gastrointestinal neutral amino acid transport in a child with Hartnup disease. The child's baseline tryptophan concentrations in serum (20 +/- 6 microM) and cerebrospinal fluid (1.0 +/- 0.2 microM) were persistently less than 50% of normal values. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, was also less than 50% of normal (21 +/- 2 ng/ml). Serum tryptophan concentrations increased only modestly and briefly after an oral challenge with 200 mg/kg of oral L-tryptophan, reflecting the absorptive defect. An oral challenge with 200 mg/kg of tryptophan ethyl ester resulted in a prompt increase in serum tryptophan to a peak of 555 microM. Sustained treatment with 20 mg/kg q6h resulted in normalization of serum (66 +/- 15 microM) and cerebrospinal fluid tryptophan concentrations (mean = 2.3 microM). Cerebrospinal fluid 5-HIAA increased to more normal concentrations (mean = 33 ng/ml). No toxicity was observed over an 8-mo period of treatment, chronic diarrhea resolved, and body weight, which had remained unchanged for 7 mo before ester therapy, increased by approximately 26%. We concluded that tryptophan ethyl ester is effective at circumventing defective gastrointestinal neutral amino acid transport and may be useful in the treatment of Hartnup disease. PMID:2472426

  16. UV radiation-induced photochemical damage of tryptophan in peptides, proteins and ocular lenses

    These studies were undertaken to investigate the possible involvement of the amino acid tryptophan in the near-ultraviolet radiation-induced photochemical alteration of peptides and proteins and the role tryptophan photolysis plays in ocular lens damage. Sample irradiations were performed to determine if tryptophan photolysis occurs with radiation in the UV-A region in comparison to photolysis induced by wavelengths in the normal absorption band of the amino acid (UV-B). Photolysis studies were carried out on free tryptophan and two dipeptides, tryptophyglycine and glycyltryptophan, in aqueous solutions at different pH values in the range 4.5-10.0 under aerated or anaerobic conditions. Rates of photolysis of these 290 nm-irradiated compounds, detected by observing tryptophan fluorescence intensity loss during irradiation, were compared and significant differences were observed for each compound which varied with pH and oxygen environment. Another series of experiments examined the photolysis of tryptophan residues in lens proteins in whole rat lenses induced by 290 nm and 298 nm dye laser radiation. Tryptophan residue photolysis was, once again, monitored by loss in tryptophan fluorescence intensity. A relationship was derived between tryptophan loss and photoproduct buildup during irradiation

  17. Mechanisms of elevation of rat brain tryptophan concentration by various doses of salicylate.

    Badawy, A. A.

    1982-01-01

    1 The roles of inhibition of liver tryptophan pyrrolase activity and of displacement of tryptophan from its binding sites on serum proteins have been investigated in relation to the increase in rat brain tryptophan concentration after administration of various doses of sodium salicylate. 2 The elevation of brain tryptophan concentration by sodium salicylate (0.5 mg/kg) was caused by inhibition of liver pyrrolase activity, whereas that by doses of the drug of 50 mg/kg and above was achieved ma...

  18. The disposition of intravenous L-tryptophan in healthy subjects and in patients with liver disease.

    Rössle, M; Herz, R; Mullen, K D; Jones, D b

    1986-01-01

    The disposition of free and of total tryptophan following an intravenous load of 1.5 g of L-tryptophan was evaluated in eight patients with non-cirrhotic liver disease, 40 patients with cirrhosis of the liver (21 Child's A, 15 Child's B, 4 Child's C) and in 14 healthy subjects. Cirrhosis affected disposition of tryptophan by (a) decreasing the clearance of both free and total tryptophan by 64% (P less than 0.001) and 34% (P less than 0.01), respectively, (b) by increasing the apparent volume ...

  19. Testing fully depleted CCD

    Casas, Ricard; Cardiel-Sas, Laia; Castander, Francisco J.; Jiménez, Jorge; de Vicente, Juan

    2014-08-01

    The focal plane of the PAU camera is composed of eighteen 2K x 4K CCDs. These devices, plus four spares, were provided by the Japanese company Hamamatsu Photonics K.K. with type no. S10892-04(X). These detectors are 200 μm thick fully depleted and back illuminated with an n-type silicon base. They have been built with a specific coating to be sensitive in the range from 300 to 1,100 nm. Their square pixel size is 15 μm. The read-out system consists of a Monsoon controller (NOAO) and the panVIEW software package. The deafualt CCD read-out speed is 133 kpixel/s. This is the value used in the calibration process. Before installing these devices in the camera focal plane, they were characterized using the facilities of the ICE (CSIC- IEEC) and IFAE in the UAB Campus in Bellaterra (Barcelona, Catalonia, Spain). The basic tests performed for all CCDs were to obtain the photon transfer curve (PTC), the charge transfer efficiency (CTE) using X-rays and the EPER method, linearity, read-out noise, dark current, persistence, cosmetics and quantum efficiency. The X-rays images were also used for the analysis of the charge diffusion for different substrate voltages (VSUB). Regarding the cosmetics, and in addition to white and dark pixels, some patterns were also found. The first one, which appears in all devices, is the presence of half circles in the external edges. The origin of this pattern can be related to the assembly process. A second one appears in the dark images, and shows bright arcs connecting corners along the vertical axis of the CCD. This feature appears in all CCDs exactly in the same position so our guess is that the pattern is due to electrical fields. Finally, and just in two devices, there is a spot with wavelength dependence whose origin could be the result of a defectous coating process.

  20. Probing the role of tryptophan-derived secondary metabolism in defense responses against Bipolaris oryzae infection in rice leaves by a suicide substrate of tryptophan decarboxylase.

    Ishihara, Atsushi; Nakao, Takahito; Mashimo, Yuko; Murai, Masatoshi; Ichimaru, Naoya; Tanaka, Chihiro; Nakajima, Hiromitsu; Wakasa, Kyo; Miyagawa, Hisashi

    2011-01-01

    Tryptophan-derived secondary metabolites, including serotonin and its hydroxycinnamic acid amides, markedly accumulate in rice leaves in response to pathogen attack. These compounds have been implicated in the physical defense system against pathogen invasion by being deposited in cell walls. Serotonin is biosynthesized from tryptophan via tryptamine, and tryptophan decarboxylase (TDC) catalyzes the first committed reaction. In this study, (S)-α-(fluoromethyl)tryptophan (S-αFMT) was utilized to investigate the effects of the inhibition of TDC on the defense responses of rice leaves. S-αFMT, enantiospecifically synthesized from L-tryptophan, effectively inhibited TDC activity extracted from rice leaves infected by Bipolaris oryzae. The inhibition rate increased dependently on the incubation time, indicating that S-αFMT served as a suicide substrate. Treatment of rice seedlings with S-αFMT suppressed accumulation of serotonin, tryptamine, and hydroxycinnamic acid amides of serotonin in a dose-dependent manner in B. oryzae-inoculated leaves. The lesions formed on seedlings treated with S-αFMT lacked deposition of brown materials, and those leaves were severely damaged in comparison with leaves without S-αFMT treatment. Administrating tryptamine to S-αFMT-treated leaves restored accumulation of tryptophan-derived secondary metabolites as well as deposition of brown material. In addition, tryptamine administration reduced damage caused by fungal infection. Accordingly, the accumulation of tryptophan-derived secondary metabolites was suggested to be part of the effective defense mechanism of rice. PMID:21112065

  1. 13C-tryptophan breath test detects increased catabolic turnover of tryptophan along the kynurenine pathway in patients with major depressive disorder

    Toshiya Teraishi; Hiroaki Hori; Daimei Sasayama; Junko Matsuo; Shintaro Ogawa; Miho Ota; Kotaro Hattori; Masahiro Kajiwara; Teruhiko Higuchi; Hiroshi Kunugi

    2015-01-01

    Altered tryptophan–kynurenine (KYN) metabolism has been implicated in major depressive disorder (MDD). The l-[1-13C]tryptophan breath test (13C-TBT) is a noninvasive, stable-isotope tracer method in which exhaled 13CO2 is attributable to tryptophan catabolism via the KYN pathway. We included 18 patients with MDD (DSM-IV) and 24 age- and sex-matched controls. 13C-tryptophan (150 mg) was orally administered and the 13CO2/12CO2 ratio in the breath was monitored for 180 min. The cumulative recove...

  2. Depletable resources and the economy.

    Heijman, W. J. M.

    1991-01-01

    The subject of this thesis is the depletion of scarce resources. The main question to be answered is how to avoid future resource crises. After dealing with the complex relation between nature and economics, three important concepts in relation with resource depletion are discussed: steady state, time preference and efficiency.For the steady state, three variants are distinguished; the stationary state, the physical steady state and the state of steady growth. It is concluded that the so-call...

  3. Gallium uptake in tryptophan-related pulmonary disease

    We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking high doses of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations

  4. Species and Cell Types Difference in Tryptophan Metabolism

    Yuki Murakami; Kuniaki Saito

    2013-01-01

    L-Tryptophan (L-TRP) is a nutritionally essential amino acid and the kynurenine (KYN) pathway is the major route of L-TRP catabolism. Besides being synthesized for proteins, L-TRP and its metabolites have critical roles for the functions of nervous and immune systems. Many researches show that optimal amounts of L-TRP in diets depend on species, developmental stages, environmental factors and health status. We have shown that KYN pathway-related enzyme activities vary among species, tissue an...

  5. Identification of Two Novel Modifications at Tryptophan Residues

    Zheng, Shuzhen; Zhang, Kai; Tian, Shanshan; He, Xiwen; Zhang, Yukui

    2015-08-01

    Protein post-translational modifications (PTMs) play important roles in cellular physiology. Mass spectrometry (MS) has been developed into a powerful tool to identify all possible protein modifications. Herein, we describe our efforts to deduce the structures of two unknown modifications at tryptophan (Trp) residues (W + 92 Da and W + 108 Da). The two modifications were further confirmed by aligning the MS/MS fragmentation of synthetic peptide with in-vivo peptide identified. Finally, the mimic experiment elucidated how two Trp modifications occur. This study, therefore, expands current knowledge of Trp modifications.

  6. Macrophage Depletion in Hypertensive Rats Accelerates Development of Cardiomyopathy

    Zandbergen, H.R.; Sharma, U.C.; S. Gupta; Verjans, J.W.H.; Borne, van den, J.J.G.C.; S Pokharel; Brakel, T.; Duijvestijn, A; Rooijen, van, J.; Maessen, J.G.; Reutelingsperger, C.P.M.; Pinto, Y.; Narula, J.; Hofstra, L

    2009-01-01

    Inflammation contributes to the process of ventricular remodeling after acute myocardial injury. To investigate the role of macrophages in the chronic process of cardiac remodeling, they were selectively depleted by intravenous administration of liposomal clodronate in heart failure-prone hypertensive Ren-2 rats from the age of 7 until 13 weeks. plain liposomes were used for comparison. Liposomal clodronate treatment reduced the number of blood monocytes and decreased the number of macrophage...

  7. Direct observation of resonance tryptophan-to-chromophore energy transfer in visible fluorescent proteins

    Visser, NV; Borst, JW; Hink, MA; van Hoek, A; Visser, AJWG

    2005-01-01

    Visible fluorescent proteins from Aequorea victoria contain next to the fluorophoric group a single tryptophan residue. Both molecules form a single donor-acceptor pair for resonance energy transfer (RET) within the protein. Time-resolved fluorescence experiments using tryptophan excitation have sho

  8. Photophysics of tryptophan in H2O, D2O, and in nonaqueous solvents

    The fluorescence properties of tryptophan in water and deuterated water have been examined. Tryptophan molecules exhibit three distinct fluorescence lifetimes in water which become longer in deuterated water; the two shorter lifetimes are present below the pK of the amino group and the long lifetime appears as the pH is raised through this pK. The steady-state quenching of tryptophan fluorescence by hydrogen ion in the region of pH less than 3 shows a definite wavelength effect, consistent with less-pronounced quenching of the subnanosecond component whose emission maximum is at 330 nm. The Stern-Volmer plots show a marked curvature in the direction of decreasing Stern-Volmer constant as [H3O+] increases. Deuterium ion also quenches tryptophan fluorescence at low pD. A kinetic scheme is proposed which reproduces both the steady-state and lifetime quenching results. Tryptophan in methanol or ethanol exhibits three fluorescence lifetimes; the relative percentage of the long component vs. the intermediate component can be varied by the addition of triethylamine or acid. In dimethyl sulfoxide, tryptophan and tryptophan deuterated at the amino and ring nirogen positions show identical behavior, both having the same decay parameters. These results are discussed in light of the theories which have recently been proposed to account for the several components in tryptophan fluorescence decay. Solvent interaction is suggested to play a critical role

  9. Tritium kinetic isotope effects on enzymatic decomposition of L-tryptophan

    The tritium kinetic isotope effect on position 2 has been determined in the reaction of decomposition of L-tryptophan, L-Trp, catalyzed by enzyme TPase, (EC 4.1.99.1). The numerical values of isotope effects in the course of reaction were obtained by the competitive method using [1-14C]-L-tryptophan as internal radiometric standard. (author)

  10. The association of sleep quality and insomnia with dietary intake of tryptophan and niacin

    Verster, J.; Fernstrand, A.; Bury, D.; Roth, T.; Garssen, J.

    2015-01-01

    Introduction: Dietary intake of tryptophan and niacin have been related to sleep. However, the sleep-promoting effects of these nutrients are still under investigation. The aim of the current study was to examine the relationship between daily dietary intake of tryptophan and niacin and sleep. Mater

  11. Regioselective Nitration of Nα,N1-Bis(trifluoroacetyl)-L-Tryptophan Methyl Ester: Efficient Synthesis of 2-Nitro and 6-Nitro-N-Trifluoroacetyl-L-Tryptophan Methyl Ester

    Osborne, Andrew S.; Som, Phanneth; Metcalf, Jessica L.; Phillips, Robert S.

    2008-01-01

    Nitration of Nα,N1-bis(trifluoroacetyl)-L-tryptophan methyl ester with HNO3 in acetic anhydride at 0° C provides Nα-trifluoroacetyl-2-nitro-L-tryptophan methyl ester in 67% yield, whereas nitration in trifluoroacetic acid at 0° C gives Nα-trifluoroacetyl-6-nitro-L-tryptophan methyl ester in 69% yield.

  12. Acetate binding induces fluorescence enhancement in tryptophan ligands

    Deka, Arup K.; Sarma, Rupam J., E-mail: rjs@gauhati.ac.in

    2014-03-15

    The anion coordination properties of bis-tryptophan dicarboxamide ligands 1–3 were investigated using fluorescence and {sup 1}H NMR spectroscopy. It was observed that the coordination of acetate anions to these ligands produced emissions at 381 nm with gradual enhancement of fluorescence. In comparison, fluoride produced minor enhancement, the addition of chloride, bromide and nitrate anions caused quenching of ligand fluorescence. {sup 1}H NMR studies revealed that the ligands coordinated to the acetate anions through the indole and amide NH groups. -- Highlights: • We have synthesized and characterized three tryptophan-based diamide ligands 1–3. • We have reported new polymorph of ligand 1 (Crystal structure) in this article. • The role of intramolecular hydrogen bonding (1 vs. 2) in anion binding was investigated. • We were able to identify the role amide/indole NH in anion binding using {sup 1}H NMR. • On the basis of {sup 1}H NMR, we have established role of aromatic CH–anion interactions during anion complexation.

  13. Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans.

    Palego, Lionella; Betti, Laura; Rossi, Alessandra; Giannaccini, Gino

    2016-01-01

    L-Tryptophan is the unique protein amino acid (AA) bearing an indole ring: its biotransformation in living organisms contributes either to keeping this chemical group in cells and tissues or to breaking it, by generating in both cases a variety of bioactive molecules. Investigations on the biology of Trp highlight the pleiotropic effects of its small derivatives on homeostasis processes. In addition to protein turn-over, in humans the pathways of Trp indole derivatives cover the synthesis of the neurotransmitter/hormone serotonin (5-HT), the pineal gland melatonin (MLT), and the trace amine tryptamine. The breakdown of the Trp indole ring defines instead the "kynurenine shunt" which produces cell-response adapters as L-kynurenine, kynurenic and quinolinic acids, or the coenzyme nicotinamide adenine dinucleotide (NAD(+)). This review aims therefore at tracing a "map" of the main molecular effectors in human tryptophan (Trp) research, starting from the chemistry of this AA, dealing then with its biosphere distribution and nutritional value for humans, also focusing on some proteins responsible for its tissue-dependent uptake and biotransformation. We will thus underscore the role of Trp biochemistry in the pathogenesis of human complex diseases/syndromes primarily involving the gut, neuroimmunoendocrine/stress responses, and the CNS, supporting the use of -Omics approaches in this field. PMID:26881063

  14. Tryptophan autofluorescence imaging of neoplasms of the human colon

    Banerjee, Bhaskar; Renkoski, Timothy; Graves, Logan R.; Rial, Nathaniel S.; Tsikitis, Vassiliki Liana; Nfonsom, Valentine; Pugh, Judith; Tiwari, Piyush; Gavini, Hemanth; Utzinger, Urs

    2012-01-01

    Detection of flat neoplasia is a major challenge in colorectal cancer screening, as missed lesions can lead to the development of an unexpected `incident' cancer prior to the subsequent endoscopy. The use of a tryptophan-related autofluorescence has been reported to be increased in murine intestinal dysplasia. The emission spectra of cells isolated from human adenocarcinoma and normal mucosa of the colon were studied and showed markedly greater emission intensity from cancerous cells compared to cells obtained from the surrounding normal mucosa. A proto-type multispectral imaging system optimized for ultraviolet macroscopic imaging of tissue was used to obtain autofluorescence images of surgical specimens of colonic neoplasms and normal mucosa after resection. Fluorescence images did not display the expected greater emission from the tumor as compared to the normal mucosa, most probably due to increased optical absorption and scattering in the tumors. Increased fluorescence intensity in neoplasms was observed however, once fluorescence images were corrected using reflectance images. Tryptophan fluorescence alone may be useful in differentiating normal and cancerous cells, while in tissues its autofluorescence image divided by green reflectance may be useful in displaying neoplasms.

  15. The crystal structure of tryptophan hydroxylase with bound amino acid substrate

    Windahl, Michael Skovbo; Petersen, Charlotte Rode; Christensen, Hans Erik Mølager; Harris, Pernille

    2008-01-01

    neurotransmitter and hormone serotonin (5-hydroxytryptamine). We have determined the 1.9 Å resolution crystal structure of the catalytic domain (Δ1−100/Δ415−445) of chicken TPH isoform 1 (TPH1) in complex with the tryptophan substrate and an iron-bound imidazole. This is the first structure of any aromatic amino...... acid hydroxylase with bound natural amino acid substrate. The iron coordination can be described as distorted trigonal bipyramidal coordination with His273, His278, and Glu318 (partially bidentate) and one imidazole as ligands. The tryptophan stacks against Pro269 with a distance of 3.9 Å between the...... iron and the tryptophan Cζ3 atom that is hydroxylated. The binding of tryptophan and maybe the imidazole has caused the structural changes in the catalytic domain compared to the structure of the human TPH1 without tryptophan. The structure of chicken TPH1 is more compact, and the loops of residues Leu...

  16. The effect of ionizing radiation on tryptophan fluorescence of thymocyte and erythrocyte plasma membranes

    The effect of γ-radiation on tryptophan fluorescence of thymocyte and erythrocyte plasma membrane preparations was studied. The intensity of tryptophan fluorescence decreased after applying radiation doses up to 15 Gy. The radiosensitivity of thymocyte membranes appeared to be higher than that of the erythrocyte ghosts. Tryptophan radiolysis did not significantly contribute to the effects of radiation. The fraction of tryptophan residues accessible for quenching by I- decreased from 0.87 in the untreated membranes to 0.63 and 0.49 in membranes after doses of 10 and 250 Gy, respectively. The effective quenching constant and the tryptophan fluorescence polarization increased after irradiation. The mechanisms producing these radiation-induced changes are discussed. (author)

  17. Rapid reversal by naloxone of the chronic effects of morphine on rat liver and brain tryptophan metabolism.

    Badawy, A. A.; Evans, M.

    1981-01-01

    The chronic morphine-induced inhibition of rat liver tryptophan pyrrolase activity and the resultant increases in tryptophan availability to the brain and brain 5-hydroxytryptamine (5-HT) synthesis are reversed within 10 min after naloxone administration. The possible involvement of hepatic tryptophan metabolism in morphine dependence is briefly discussed.

  18. TRYPTOPHAN: EFFECTS ON NEUTOTRANSMITTERS, BEHAVIOR, MEAT QUALITY, AND THE RESULTS OF CURRENT REQUIREMENT STUDIES IN NURSERY PIGS

    Tryptophan is one of most interesting and complex amino acids. The lack of sensitive methods for tryptophan determination in proteins and biological fluids, low content in common feedstuffs, low product availability, high cost of crystalline tryptophan, and the high degree of variability associated...

  19. Nonlinear lower hybrid wave depletion

    Two numerical ray tracing codes with focusing are used to compute lower hybrid daughter wave amplification by quasi-mode parametric decay. The first code, LHPUMP provides a numerical pump model on a grid. This model is used by a second code, LHFQM which computes daughter wave amplification inside the pump extent and follows the rays until their energy is absorbed by the plasma. An analytic model is then used to estimate pump depletion based on the numerical results. Results for PLT indicate strong pump depletion at the plasma edge at high density operation for the 800 Mhz wave frequency, but weak depletion for the 2.45 Ghz experiment. This is proposed to be the mechanism responsible for the high density limit for current drive as well as for the difficulty to heat ions

  20. Correlation of tryptophan fluorescence intensity decay parameters with sup 1 H NMR-determined rotamer conformations: (tryptophan sup 2 )oxytocin

    Ross, J.B.A.; Schwartz, G.P.; Laws, W.R. (Mount Sinai, New York, NY (United States)); Wyssbrod, H.R.; Porter, R.A. (Univ. of Louisville, KY (United States)); Michaels, C.A. (Swarthmore Coll., PA (United States))

    1992-02-18

    While the fluorescence decay kinetics of tyrosine model compounds can be explained in terms of heterogeneity derived from the three ground-state {chi}{sup 1} rotamers, a similar correlation has yet to be directly observed for a tryptophan residue. In addition, the asymmetric indole ring might also lead to heterogeneity from {chi}{sup 2} rotations. In this paper, the time-resolved and steady-state fluorescence properties of (tryptophan{sup 2})oxytocin at pH 3 are presented and compared with {sup 1}H NMR results. According to the unrestricted analyses of individual fluorescence decay curves taken as a function of emission wavelength-independent decay constants, only three exponential terms are required. In addition, the preexponential weighting factors (amplitudes) have the same relative relationship (weights) as the {sup 1}H NMR-determined {chi}{sup 1} rotamer populations of the indole side chain. {sup 15}N was used in heteronuclear coupling experiments to confirm the rotamer assignments. Inclusion of a linked function restricting the decay amplitudes to the {chi}{sup 1} rotamer populations in the individual decay curve analyses and in the global analysis confirms this correlation. According to qualitative nuclear Overhauser data, there are two {chi}{sup 2} populations.

  1. The effect of pH on the aerobic and anaerobic photolysis of tryptophan and some tryptophan-containing dipeptides

    Rates of photolysis, quantum yields of fluorescence, and fluorescence emission maxima for the dipeptides glycyltryptophan (Gly-Trp) and tryptophylglycine (Trp-Gly) and for free tryptophan (Trp) were determined under both degassed and aerated conditions in the pH range 4.5-10.0. The photolyses were performed at 250C using 290 nm radiation from a 1000 W xenon lamp. Photolysis rates were determined by monitoring tryptophan fluorescence loss with time. It was found that Trp-Gly and free Trp showed similar behavior in that their fluorescence quantum yields and photolysis rates increased significantly above neutral pH. In contrast, the Gly-Trp fluorescence yield was smaller than that of Trp or Trp-Gly, showing no significant increase at high pH and the photolysis rate for Gly-Trp decreased with increasing pH. In comparing aerated to degassed samples, degassing had a far greater effect on the photolysis rates of Trp and Trp-Gly than on the photolysis rate of Gly-Trp especially at higher pH. But, degassing did not change the relative fluorescence quantum yields or fluorescence emission maxima of any of the three compounds. Possible mechanisms for photolysis under various experimental conditions were examined in light of the data. (author)

  2. Ventilatory adaptation to hypoxia occurs in serotonin-depleted rats.

    Olson, E B

    1987-08-01

    To test the hypothesis that serotonin mediated respiratory activity is involved in ventilatory adaptation to hypoxia, rats were treated with parachlorophenylalanine (PCPA), a potent, long-acting inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin. In normoxia, a single, intraperitoneal injection of 300 mg PCPA/kg body weight decreased the Paco2 from a control level at 39.1 +/- 0.6 Torr (mean +/- 95% confidence limits) to 34.0 +/- 0.6 Torr measured during a period from 1 to 48 h following PCPA treatment. This PCPA-produced hyperventilation corresponds to an increase of 3.7 +/- 0.5 in the VA (BTPS)/Vco2 (STPD) ratio. Hyperventilation during ventilatory adaptation to hypoxia (PIO2 approximately equal to 90 Torr) was superimposed in an additive fashion on the underlying hyperventilation due to PCPA pretreatment. Specifically, PCPA pretreatment caused an average 3.5 +/- 1.2 increase in the VA/VCO2 ratio determined in acute (1 h) hypoxia, chronic (24 h) hypoxia and acute return to normoxia following chronic hypoxia. Since ventilatory adaptation to hypoxia occurred in rats treated with PCPA, the prolonged, serotonin mediated respiratory activity described by Millhorn et al. (1980b) is probably not important in ventilatory acclimatization to - or deacclimatization from - hypoxia. PMID:2957766

  3. Modelling the evolution of the archaeal tryptophan synthase

    Merkl Rainer

    2007-04-01

    Full Text Available Abstract Background Microorganisms and plants are able to produce tryptophan. Enzymes catalysing the last seven steps of tryptophan biosynthesis are encoded in the canonical trp operon. Among the trp genes are most frequently trpA and trpB, which code for the alpha and beta subunit of tryptophan synthase. In several prokaryotic genomes, two variants of trpB (named trpB1 or trpB2 occur in different combinations. The evolutionary history of these trpB genes is under debate. Results In order to study the evolution of trp genes, completely sequenced archaeal and bacterial genomes containing trpB were analysed. Phylogenetic trees indicated that TrpB sequences constitute four distinct groups; their composition is in agreement with the location of respective genes. The first group consisted exclusively of trpB1 genes most of which belonged to trp operons. Groups two to four contained trpB2 genes. The largest group (trpB2_o contained trpB2 genes all located outside of operons. Most of these genes originated from species possessing an operon-based trpB1 in addition. Groups three and four pertain to trpB2 genes of those genomes containing exclusively one or two trpB2 genes, but no trpB1. One group (trpB2_i consisted of trpB2 genes located inside, the other (trpB2_a of trpB2 genes located outside the trp operon. TrpA and TrpB form a heterodimer and cooperate biochemically. In order to characterise trpB variants and stages of TrpA/TrpB cooperation in silico, several approaches were combined. Phylogenetic trees were constructed for all trp genes; their structure was assessed via bootstrapping. Alternative models of trpB evolution were evaluated with parsimony arguments. The four groups of trpB variants were correlated with archaeal speciation. Several stages of TrpA/TrpB cooperation were identified and trpB variants were characterised. Most plausibly, trpB2 represents the predecessor of the modern trpB gene, and trpB1 evolved in an ancestral bacterium

  4. Substitutions of Thr30 provide mechanistic insight into tryptophan-mediated activation of TRAP binding to RNA

    Payal, Vandana; Gollnick, Paul

    2006-01-01

    TRAP is an 11 subunit RNA binding protein that regulates expression of genes involved in tryptophan biosynthesis and transport in Bacillus subtilis. TRAP is activated to bind RNA by binding up to 11 molecules of l-tryptophan in pockets formed by adjacent subunits. The precise mechanism by which tryptophan binding activates TRAP is not known. Thr30 is in the tryptophan binding pocket. A TRAP mutant in which Thr30 is substituted with Val (T30V) does not bind tryptophan but binds RNA constitutiv...

  5. DOPAMINE DEPLETION SLOWS RETINAL TRANSMISSION

    In male hooded rats, depletion of norepinephrine and dopamine by a-methyl-paratyrosine (AMT) significantly increased the latencies of early peaks in flash-evoked potentials recorded from the visual cortex, lateral geniculate nucleus, and optic tract. These effects were not produc...

  6. Role for tryptophan in regulation of protein synthesis in porcine muscle

    Experiments were conducted to determine the effect of varying concentrations of dietary tryptophan on growth rate and protein synthesis in edible muscle tissues of growing swine. A total of 45 immature swine (initial weight approximately 24 kg) were fed corn-gelatin diets containing 0.5 (n = 8), 0.8 (n = 10), 1.3 (n = 10), 1.5 (n = 7) or 2.0 (n = 10) g tryptophan/kg diet for 35 d. Animals fed 0.5 and 0.8 g tryptophan/kg grew more slowly, consumed less feed and had a lower efficiency of feed utilization than animals fed higher concentrations of tryptophan. Thirty similar animals were used in a second experiment. Diets containing 0.5, 0.8, 1.0, 1.5 or 2.0 g tryptophan/kg diet (n = 6) were fed for 14 d, after which all animals were killed and samples were taken of longissimus dorsi, triceps brachii and biceps femoris. Protein synthetic activity was determined by monitoring the incorporation of [14C]phenylalanine into protein in vitro. There was no significant difference in synthetic activity between different muscle types. There was no effect of diet on the activity of the muscle soluble protein fraction. The activity of the muscle ribosomal fraction, however, was positively correlated with increasing concentrations of dietary tryptophan. It was concluded that tryptophan has the potential to regulate muscle protein synthesis in a manner beyond serving simply as a component of protein

  7. Was the Chlamydial Adaptative Strategy to Tryptophan Starvation an Early Determinant of Plastid Endosymbiosis?

    Cenci, Ugo; Ducatez, Mathieu; Kadouche, Derifa; Colleoni, Christophe; Ball, Steven G

    2016-01-01

    Chlamydiales were recently proposed to have sheltered the future cyanobacterial ancestor of plastids in a common inclusion. The intracellular pathogens are thought to have donated those critical transporters that triggered the efflux of photosynthetic carbon and the consequent onset of symbiosis. Chlamydiales are also suspected to have encoded glycogen metabolism TTS (Type Three Secretion) effectors responsible for photosynthetic carbon assimilation in the eukaryotic cytosol. We now review the reasons underlying other chlamydial lateral gene transfers evidenced in the descendants of plastid endosymbiosis. In particular we show that half of the genes encoding enzymes of tryptophan synthesis in Archaeplastida are of chlamydial origin. Tryptophan concentration is an essential cue triggering two alternative modes of replication in Chlamydiales. In addition, sophisticated tryptophan starvation mechanisms are known to act as antibacterial defenses in animal hosts. We propose that Chlamydiales have donated their tryptophan operon to the emerging plastid to ensure increased synthesis of tryptophan by the plastid ancestor. This would have allowed massive expression of the tryptophan rich chlamydial transporters responsible for symbiosis. It would also have allowed possible export of this valuable amino-acid in the inclusion of the tryptophan hungry pathogens. Free-living single cell cyanobacteria are devoid of proteins able to transport this amino-acid. We therefore investigated the phylogeny of the Tyr/Trp transporters homologous to E. coli TyrP/Mre and found yet another LGT from Chlamydiales to Archaeplastida thereby considerably strengthening our proposal. PMID:27446814

  8. Functional roles of Tryptophan residues in diketoreductase from Acinetobacter baylyi

    Yan Huang1, Zhuo Lu1, Min Ma1, Nan Liu1 & Yijun Chen1,2,*

    2012-08-01

    Full Text Available Diketoreductase (DKR from Acinetobacter baylyi contains twotryptophan residues at positions 149 and 222. Trp-149 andTrp-222 are located along the entry path of substrate into activesite and at the dimer interface of DKR, respectively. Single anddouble substitutions of these positions were generated to probethe roles of tryptophan residues. After replacing Trp with Alaand Phe, biochemical and biophysical characteristics of themutants were thoroughly investigated. Enzyme activity andsubstrate binding affinity of W149A and W149F wereremarkably decreased, suggesting that Trp-149 regulates theposition of substrate at the binding site. Meanwhile, enzymeactivity of W222F was increased by 1.7-fold while W222A wascompletely inactive. In addition to lower thermostability ofTrp-222 mutants, molecular modeling of the mutants revealedthat Trp-222 is vital to protein folding and dimerization of theenzyme.

  9. Doxycycline induced photodamage to human neutrophils and tryptophan

    Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 μM doxycycline. At increasing light fluence the locomotion, chemiluminescence and glucose oxidation (by the hexose monophosphate shunt) of the neutrophils steadily decreased. The photodamage increased with increasing preincubation temperature and time and was enhanced in D2O, reduced in azide and abolished in anaerobiosis. Superoxide dismutase, catalase or mannitol did not influence the photodamage. Photooxidation of tryptophan in the presence of doxycycline was increased 9-10-fold in D2O and nearly abolished in the presence of 0.25 mM NaN3, indicating that singlet oxygen is the most important reactive oxygen species in the doxycycline-induced photodamage. The results may explain some of the features of tetracycline-induced photosensitivity and why other authors have obtained diverging results when studying the influence of tetracyclines on neutrophil functions. (author)

  10. Doxycycline induced photodamage to human neutrophils and tryptophan

    Sandberg, S.; Glette, J.; Hopen, G.; Solberg, C.O. (Haukeland Sykehus, Bergen (Norway))

    1984-01-01

    Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 ..mu..M doxycycline. At increasing light fluence the locomotion, chemiluminescence and glucose oxidation (by the hexose monophosphate shunt) of the neutrophils steadily decreased. The photodamage increased with increasing preincubation temperature and time and was enhanced in D/sub 2/O, reduced in azide and abolished in anaerobiosis. Superoxide dismutase, catalase or mannitol did not influence the photodamage. Photooxidation of tryptophan in the presence of doxycycline was increased 9-10-fold in D/sub 2/O and nearly abolished in the presence of 0.25 mM NaN/sub 3/, indicating that singlet oxygen is the most important reactive oxygen species in the doxycycline-induced photodamage. The results may explain some of the features of tetracycline-induced photosensitivity and why other authors have obtained diverging results when studying the influence of tetracyclines on neutrophil functions.