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| L-tryptophan |
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| CHEBI:16828 |
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| L-tryptophan |
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| The L-enantiomer of tryptophan. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:21407, CHEBI:45988, CHEBI:46125, CHEBI:46086, CHEBI:46225, CHEBI:184633, CHEBI:6310, CHEBI:13178
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| ChemicalBook:CB3750054, eMolecules:26755894, eMolecules:533030, ZINC000000083315 |
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more structures >>
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| Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic beta carbon substituent. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3 (niacin). It is encoded by the codon UGG.
Like other amino acids, tryptophan is a zwitterion at physiological pH where the amino group is protonated (–NH+3; pKa = 9.39) and the carboxylic acid is deprotonated ( –COO−; pKa = 2.38).
Humans and many animals cannot synthesize tryptophan: they need to obtain it through their diet, making it an essential amino acid.
Tryptophan is named after the digestive enzymes trypsin, which were used in its first isolation from casein proteins. It was assigned the one-letter symbol W based on the double ring being visually suggestive to the bulky letter. |
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Read full article at Wikipedia
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InChI=1S/C11H12N2O2/c12- 9(11(14)15)5-7-6-13-10-4-2-1-3-8(7)10/h1-4,6,9,13H,5,12H2,(H,14,15)/t9-/m0/s1 |
| QIVBCDIJIAJPQS-VIFPVBQESA-N |
| N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Saccharomyces cerevisiae
(NCBI:txid4932)
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Source: yeast.sf.net
See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
Saccharomyces cerevisiae metabolite
Any fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae ).
micronutrient
Any nutrient required in small quantities by organisms throughout their life in order to orchestrate a range of physiological functions.
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
Daphnia magna metabolite
A Daphnia metabolite produced by the species Daphnia magna.
(via tryptophan )
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antidepressant
Antidepressants are mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions.
nutraceutical
A product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
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View more via ChEBI Ontology
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(2S)-2-amino-3-(1H-indol-3-yl)propanoic acid
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IUPAC
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(S)-α-amino-1H-indole-3-propanoic acid
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NIST Chemistry WebBook
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(S)-alpha-Amino-beta-(3-indolyl)-propionic acid
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KEGG COMPOUND
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(S)-tryptophan
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NIST Chemistry WebBook
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L-(−)-tryptophan
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NIST Chemistry WebBook
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L-β-3-indolylalanine
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NIST Chemistry WebBook
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L-Tryptophan
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KEGG COMPOUND
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L-tryptophan
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ChEBI
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Trp
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ChEBI
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Tryptophan
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KEGG COMPOUND
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TRYPTOPHAN
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PDBeChem
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W
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ChEBI
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2780
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DrugCentral
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C00001396
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KNApSAcK
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C00078
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KEGG COMPOUND
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D00020
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KEGG DRUG
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DB00150
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DrugBank
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ECMDB00929
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ECMDB
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HMDB0000929
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HMDB
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TRP
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PDBeChem
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TRP
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MetaCyc
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Tryptophan
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Wikipedia
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YMDB00126
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YMDB
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| View more database links |
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51434
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Gmelin Registry Number
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Gmelin
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73-22-3
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CAS Registry Number
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KEGG COMPOUND
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73-22-3
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CAS Registry Number
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ChemIDplus
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73-22-3
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CAS Registry Number
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NIST Chemistry WebBook
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86197
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Reaxys Registry Number
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Reaxys
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Shimazaki J, Furukawa S, Ogihara H, Morinaga Y (2012)
L-Tryptophan prevents Escherichia coli biofilm formation and triggers biofilm degradation.
Biochemical and biophysical research communications 419, 715-718 [PubMed:22386992]
[show Abstract]
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. | Özcan A, Şahin Y (2012)
A novel approach for the selective determination of tryptophan in blood serum in the presence of tyrosine based on the electrochemical reduction of oxidation product of tryptophan formed in situ on graphite electrode.
Biosensors & bioelectronics 31, 26-31 [PubMed:22071091]
[show Abstract]
In this study, a novel method was proposed for the selective determination of tryptophan (TRP) in blood serum in the presence of tyrosine. This method is based on the electrochemical reduction of 2-amino-3-(5-oxo-3,5-dihydro-2H-indol-3-yl)-propionic acid (5-O-3,5DH-TRP) formed by the oxidation of TRP on the electrochemically treated pencil graphite (ETPG) electrode surface at a suitable potential value. The parameters affecting the TRP determination were deeply investigated. The optimal pH value was determined as 3. The highest reduction current intensity was obtained at the accumulation potential and time values of +0.95 V and 120 s, respectively. The reduction peak current values of 5-O-3,5DH-TRP versus TRP concentration at the ETPG electrode showed linearity in the range from 0.5 μM to 50.0 μM (R(2)=0.9962) with a detection limit of 0.05 μM (S/N=3). The reduction peak intensity of 5-O-3,5DH-TRP on the ETPG electrode showed no significant change in the presence of different interfering substances. The analytical application of the proposed novel method was successfully tested by using human blood serum samples. | Chen X, Dai H, Li J, Huang X, Wei Z (2012)
The effects of biological environments on the electron-relay functionality of tryptophan residues in proteins.
Chemphyschem : a European journal of chemical physics and physical chemistry 13, 183-192 [PubMed:22162421]
[show Abstract]
Clarifying the contribution of tryptophan (Trp) to electron-transfer (ET) processes in different protein surroundings can help to understand the effective pathway of ET in proteins. Interactions between Trp residues and protein microsurroundings involve intermolecular H-bonds, cation and π-electron clouds of aromatic rings, the secondary structure and π orbital of aromatic rings, and so on. Detailed analyses reveal that the microsurroundings play an important role in modulating the electron-relay function of Trp in proteins. Generally, microsurroundings with strong Lewis acidity inhibit electron hole transport through Trp residues. Systems with weak Lewis acidity finely tune the electron-relay ability of Trp in proteins, while those with strong Lewis basicity strongly enhance the electron-relay ability of Trp residues. | Sa M, Ying L, Tang AG, Xiao LD, Ren YP (2012)
Simultaneous determination of tyrosine, tryptophan and 5-hydroxytryptamine in serum of MDD patients by high performance liquid chromatography with fluorescence detection.
Clinica chimica acta; international journal of clinical chemistry 413, 973-977 [PubMed:22402312]
[show Abstract]
BackgroundTyrosine (Tyr), Tryptophan (Trp) and 5-hydroxytryptamine (5-HT) are important amino acids in vivo and have been hypothesized to be involved in many mental disorders. We developed a rapid and sensitive HPLC method for simultaneous measurement of serum Tyr, Trp and 5-HT and explored the clinical significances of Tyr, Trp and 5-HT and the 5-HT/Trp ratio for patients with major depressive disorder (MDD) disease.MethodsSerum samples were deproteinized by 5% perchloric acid and separated on an Atlantis C18 column (4.6 × 150 mm, 5 μm) with the mobile phase consisting of 0.1 mol/l KH(2)PO(4) and methanol (85:15, V/V).The eluates were monitored by the fluorescence detection with programmed wavelength.ResultsAnalysis was achieved in <12.0 min. The limits of quantification were 0.014, 0.005, and 0.024 μmol/l for Tyr, Trp and 5-HT, respectively. Reproducibility and recovery were satisfactory. Tyr, Trp and 5-HT and the 5-HT/Trp ratio were significantly decreased in patients with MDD.ConclusionsIn diseases, like MDD, Tyr, Trp and 5-HT play an important role. This method can potentially be applied as prognostic or diagnostic tool or even to follow the evolution of the illness or of the treatment. | Schallreuter KU, Salem MA, Gibbons NC, Martinez A, Slominski R, Lüdemann J, Rokos H (2012)
Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 1: Epidermal H2O2/ONOO(-)-mediated stress abrogates tryptophan hydroxylase and dopa decarboxylase activities, leading to low serotonin and melatonin levels.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26, 2457-2470 [PubMed:22415302]
[show Abstract]
Vitiligo is characterized by a progressive loss of inherited skin color. The cause of the disease is still unknown. To date, there is accumulating in vivo and in vitro evidence for massive oxidative stress via hydrogen peroxide (H(2)O(2)) and peroxynitrite (ONOO(-)) in the skin of affected individuals. Autoimmune etiology is the favored theory. Since depletion of the essential amino acid L-tryptophan (Trp) affects immune response mechanisms, we here looked at epidermal Trp metabolism via tryptophan hydroxylase (TPH) with its downstream cascade, including serotonin and melatonin. Our in situ immunofluorescence and Western blot data reveal significantly lower TPH1 expression in patients with vitiligo. Expression is also low in melanocytes and keratinocytes under in vitro conditions. Although in vivo Fourier transform-Raman spectroscopy proves the presence of 5-hydroxytryptophan, epidermal TPH activity is completely absent. Regulation of TPH via microphthalmia-associated transcription factor and L-type calcium channels is severely affected. Moreover, dopa decarboxylase (DDC) expression is significantly lower, in association with decreased serotonin and melatonin levels. Computer simulation supports H(2)O(2)/ONOO(-)-mediated oxidation/nitration of TPH1 and DDC, affecting, in turn, enzyme functionality. Taken together, our data point to depletion of epidermal Trp by Fenton chemistry and exclude melatonin as a relevant contributor to epidermal redox balance and immune response in vitiligo. | Schallreuter KU, Salem MA, Gibbons NC, Maitland DJ, Marsch E, Elwary SM, Healey AR (2012)
Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 2: Epidermal H2O2/ONOO(-)-mediated stress in vitiligo hampers indoleamine 2,3-dioxygenase and aryl hydrocarbon receptor-mediated immune response signaling.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26, 2471-2485 [PubMed:22415306]
[show Abstract]
Vitiligo is characterized by a mostly progressive loss of the inherited skin color. The cause of the disease is still unknown, despite accumulating in vivo and in vitro evidence of massive oxidative stress via hydrogen peroxide (H(2)O(2)) and peroxynitrite (ONOO(-)) in the skin of affected individuals. The most favored hypothesis is based on autoimmune mechanisms. Since depletion of the essential amino acid L-tryptophan (Trp) severely affects various immune responses, we here looked at Trp metabolism and signaling in these patients. Our in vivo and in vitro data revealed total absence of epidermal Trp hydroxylase activities and the presence of H(2)O(2)/ONOO(-) deactivated indoleamine 2,3-dioxygenase. Aryl hydrocarbon receptor signaling is severely impaired despite the ligand (Trp dimer) being formed, as shown by mass spectrometry. Loss of this signal is supported by the absence of downstream signals (COX-2 and CYP1A1) as well as regulatory T-lymphocytes and by computer modeling. In vivo Fourier transform Raman spectroscopy confirmed the presence of Trp metabolites together with H(2)O(2) supporting deprivation of the epidermal Trp pool by Fenton chemistry. Taken together, our data support a long-expressed role for in loco redox balance and a distinct immune response. These insights could open novel treatment strategies for this disease. | Koopmans SJ, van der Staay FJ, Le Floc'h N, Dekker R, van Diepen JT, Jansman AJ (2012)
Effects of surplus dietary L-tryptophan on stress, immunology, behavior, and nitrogen retention in endotoxemic pigs.
Journal of animal science 90, 241-251 [PubMed:21856896]
[show Abstract]
The possible beneficial effects of surplus dietary Trp (+5 g of Trp/kg of diet) on factors related to stress, immunology, behavior, and N retention were investigated in postweaning piglets (approximately 15 kg of BW) challenged for 10 d with intravenous bacterial lipopolysaccharide (from Escherichia coli). Two diets fed restrictively (732 kJ of NE/kg of BW(0.75)/d) were compared, 1) a basal diet (apparent ileal digestible Trp = 1.9 g/kg; the recommended amount of Trp to warrant near-optimal growth in nonendotoxemic piglets), and 2) a Trp-enriched basal diet (+5 g of free l-Trp/kg), with 8 individually housed piglets per diet. Pooled salivary cortisol, but not plasma cortisol sampled at euthanasia, showed a tendency (P = 0.07) toward reduced concentrations in the Trp group (1.1 vs. 1.4 ng/mL; pooled SE = 0.1 ng/mL). Plasma C-reactive protein was reduced (P = 0.04) in the Trp group (0.9 vs. 5.0 mg/L; pooled SE = 1.3 mg/L), but haptoglobin, IL-6, tumor necrosis factor α, and lipopolysaccharide-induced fever were similar between the 2 dietary treatments. Physical activity related to approaching a human showed a tendency (P = 0.08) toward increased latency time in the Trp group (101 vs. 60 s; pooled SE = 16 s), but the times spent standing, sitting, and lying were similar between dietary treatments. The ADFI, ADG (346 vs. 302 g/d; pooled SE = 14 g/d; P = 0.11), body N retention (11.6 vs. 11.0 g/d; pooled SE = 0.2 g/d; P = 0.18), and G:F (0.55 vs. 0.49; pooled SE = 0.03; P = 0.17) were not different between the groups fed Trp and the basal diet. In conclusion, surplus dietary Trp had limited effects on stress, immunology, behavior, and N retention in a pig model of systemic endotoxemia. | Efimov I, Basran J, Sun X, Chauhan N, Chapman SK, Mowat CG, Raven EL (2012)
The mechanism of substrate inhibition in human indoleamine 2,3-dioxygenase.
Journal of the American Chemical Society 134, 3034-3041 [PubMed:22299628]
[show Abstract]
Indoleamine 2,3-dioxygenase catalyzes the O(2)-dependent oxidation of L-tryptophan (L-Trp) to N-formylkynurenine (NFK) as part of the kynurenine pathway. Inhibition of enzyme activity at high L-Trp concentrations was first noted more than 30 years ago, but the mechanism of inhibition has not been established. Using a combination of kinetic and reduction potential measurements, we present evidence showing that inhibition of enzyme activity in human indoleamine 2,3-dioxygenase (hIDO) and a number of site-directed variants during turnover with L-tryptophan (L-Trp) can be accounted for by the sequential, ordered binding of O(2) and L-Trp. Analysis of the data shows that at low concentrations of L-Trp, O(2) binds first followed by the binding of L-Trp; at higher concentrations of L-Trp, the order of binding is reversed. In addition, we show that the heme reduction potential (E(m)(0)) has a regulatory role in controlling the overall rate of catalysis (and hence the extent of inhibition) because there is a quantifiable correlation between E(m)(0) (that increases in the presence of L-Trp) and the rate constant for O(2) binding. This means that the initial formation of ferric superoxide (Fe(3+)-O(2)(•-)) from Fe(2+)-O(2) becomes thermodynamically less favorable as substrate binds, and we propose that it is the slowing down of this oxidation step at higher concentrations of substrate that is the origin of the inhibition. In contrast, we show that regeneration of the ferrous enzyme (and formation of NFK) in the final step of the mechanism, which formally requires reduction of the heme, is facilitated by the higher reduction potential in the substrate-bound enzyme and the two constants (k(cat) and E(m)(0)) are shown also to be correlated. Thus, the overall catalytic activity is balanced between the equal and opposite dependencies of the initial and final steps of the mechanism on the heme reduction potential. This tuning of the reduction potential provides a simple mechanism for regulation of the reactivity, which may be used more widely across this family of enzymes. | Bitzer-Quintero OK, Dávalos-Marín AJ, Ortiz GG, Meza AR, Torres-Mendoza BM, Robles RG, Huerta VC, Beas-Zárate C (2010)
Antioxidant activity of tryptophan in rats under experimental endotoxic shock.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 64, 77-81 [PubMed:19896323]
[show Abstract]
Tryptophan (TRP), the precursor of the scavenger or immunomodulator molecules melatonin (MLT) and picolinic acid, can be found in the diet; and could be an alternative nutritional supplement used to regulate the immune response in the generation of free radicals. In an experimental model, the systemic administration of lipopolysaccharide (LPS), to promote the synthesis of pro-inflammatory cytokines, reactive oxygen species, and antioxidant enzymes, was performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein). Lung tissue was evaluated for levels of the products of lipoperoxidation (LPO's), malonaldehyde (MDA) and 4-hydroxy alkenals (4-HDA); nitrites (NO2), glutathione peroxidase (Gpx) enzyme activity, and the serum concentration of interferon-gamma (IFN-gamma), which were measured in the following groups: control (CTRL), LPS, MLT, TRP, LPS plus MLT (LPS+MLT), and LPS plus TRP (LPS+TRP). Results showed that the lung tissue levels of MDA and 4-HDA in the LPS+TRP group were significantly lower than in the TRP group. Statistically significant differences were not observed in nitric oxide levels among the groups LPS+MLT and LPS+TRP compared to the group under endotoxic shock (LPS). The Gpx enzyme activity was modified in the LPS+MLT vs the LPS group, but the difference was not statistically significant. The LPS+MLT group showed a smaller serum concentration (98%) of IFN-gamma than the LPS group. Statistically significant differences were not observed among the animals of the LPS+TRP and the LPS groups. | Balas F, Manzano M, Colilla M, Vallet-Regí M (2008)
L-Trp adsorption into silica mesoporous materials to promote bone formation.
Acta biomaterialia 4, 514-522 [PubMed:18234569]
[show Abstract]
The properties of ordered mesoporous silicas as bioactive materials, able to induce bone-tissue regeneration, have been combined with their abilities to host and release specific biomolecules in a controlled fashion. The possibility of locally deliver peptides and proteins is of great scientific importance because it opens new paths for the design of implantable biomaterials than can promote bone formation where needed. These biomaterials can host such biofactors, and their adsorption can be enhanced by chemically modifying the silica surface, with the aim of encouraging host-guest interaction and, thereby, increasing the loading capacity of the biomaterial matrix. L-Tryptophan (L-Trp) is a hydrophobic amino acid present in the three-dimensional structure of numerous proteins, and it is used here as model system to predict peptide delivery systems. Unmodified, silanol-rich, bioactive SBA-15 ordered mesoporous silica has been found to be incapable of confining L-Trp in its mesopores due to the hydrophobic character of this molecule. Organically modifying SBA-15 with quaternary amines results in approximately two-thirds of the silica surface being functionalized, increases the surface hydrophobicity allowing an increased L-Trp loading, and also induces different release kinetics. The control of the L-Trp release is the first step in controlled and localized protein delivery technologies, and opens novel perspectives for designing bioactive silica-based devices suitable for bone-healing applications. | Carminatti CA, Oliveira IL, Recouvreux DO, Antônio RV, Porto LM (2008)
Anthranilate synthase subunit organization in Chromobacterium violaceum.
Genetics and molecular research : GMR 7, 830-838 [PubMed:18949702]
[show Abstract]
Tryptophan is an aromatic amino acid used for protein synthesis and cellular growth. Chromobacterium violaceum ATCC 12472 uses two tryptophan molecules to synthesize violacein, a secondary metabolite of pharmacological interest. The genome analysis of this bacterium revealed that the genes trpA-F and pabA-B encode the enzymes of the tryptophan pathway in which the first reaction is the conversion of chorismate to anthranilate by anthranilate synthase (AS), an enzyme complex. In the present study, the organization and structure of AS protein subunits from C. violaceum were analyzed using bioinformatics tools available on the Web. We showed by calculating molecular masses that AS in C. violaceum is composed of alpha (TrpE) and beta (PabA) subunits. This is in agreement with values determined experimentally. Catalytic and regulatory sites of the AS subunits were identified. The TrpE and PabA subunits contribute to the catalytic site while the TrpE subunit is involved in the allosteric site. Protein models for the TrpE and PabA subunits were built by restraint-based homology modeling using AS enzyme, chains A and B, from Salmonella typhimurium (PDB ID 1I1Q). | Mainardi P, Leonardi A, Albano C (2008)
Potentiation of brain serotonin activity may inhibit seizures, especially in drug-resistant epilepsy.
Medical hypotheses 70, 876-879 [PubMed:17826001]
[show Abstract]
In spite of the large number of antiepileptic drugs (AEDs) actually available, the problem of drug-resistant epilepsy has not been solved. No AEDs are efficacious in patients with pharmacoresitant epilepsy, so new hypothesises about the mechanisms of pharmacoresistance are needed. In the last years the ideas on the role of brain serotonin in epilepsy have been turned upside down: increasing the available brain serotonin is thought now to have an antiepileptic effect. Antidepressant drugs like selective serotonin re-uptake inhibitors, i.e., fluoxetine, have proved to be useful in seizure control. Tryptophan (Trp), an essential amino acid, is the only brain precursor of serotonin, it competes with the other large neutral amino acids (LNAAs) for the carrier of blood-brain barrier (BBB). Our own data has shown a lowering of plasmatic LNAA levels in epileptic patients, on the basis of these results we could estimate a decrease of a 1/3 in the Trp brain intake rate in epileptics in respect to controls. Increasing plasmatic Trp levels increases brain serotonin synthesis. Trp and 5-hydroxytryptophan (5-HTP) were tested as an add on in epilepsy, but the clinical outcome was controversial. Free amino acids are not fully adsorbed by the gastro-intestinal system, furthermore LNAAs, and also 5-HTP is a LNAA, compete to cross the intestinal membrane for the same carrier, like for the BBB. The best way to increase the plasmatic Trp level is a protein rich in Trp and poor in the other LNAAs. Unfortunately Trp is a limited amino acid in proteins. We report the clinical results obtained by adding a whey protein to the antiepileptic therapy of drug-resistant epileptic patients: alpha-lactoalbumin, rich in Trp and poor in the other LNAAs. | Sanjaya, Hsiao PY, Su RC, Ko SS, Tong CG, Yang RY, Chan MT (2008)
Overexpression of Arabidopsis thaliana tryptophan synthase beta 1 (AtTSB1) in Arabidopsis and tomato confers tolerance to cadmium stress.
Plant, cell & environment 31, 1074-1085 [PubMed:18419734]
[show Abstract]
Tryptophan (Trp) is an essential amino acid in humans, and in plants, it plays a major role in the regulation of plant development and defence responses. However, little is known about Trp-mediated cadmium (Cd) tolerance. Gene expression analysis showed that Arabidopsis thaliana tryptophan synthase beta 1 (AtTSB1) is up-regulated in plants treated with Cd; hence, we investigated whether this gene is involved in Cd tolerance. Exogenous application of Trp to wild-type Arabidopsis enhances Cd tolerance. Cd tolerance in the Trp-overproducing mutant trp5-1 was associated with high chlorophyll levels and low lipid peroxidation, as indicated by malondialdehyde 4-hydroxyalkenal level, whereas the wild-type developed symptoms of severe chlorosis. Moreover, the Trp-auxotroph mutant trp2-1 was sensitive to Cd. CaMV 35S promoter-driven AtTSB1 enhanced Trp accumulation and improved Cd tolerance in transgenic Arabidopsis and tomato plants without increasing the level of Cd. Moreover, reverse transcription-polymerase chain reaction confirmed that enhanced level of Trp in AtTSB1 transgenic Arabidopsis plants affected the expression of AtZIP4 and AtZIP9 metal transporters, which interfered with Cd ion trafficking, a mechanism of transcriptional regulation that does not exist in wild-type plants. Overexpression of AtTSB1 in transgenic tomato also produced higher Trp synthase-beta enzyme activity than that in wild-type plants. These results implicate that Trp could be involved in Cd defence. | Igarashi N, Onoue S, Tsuda Y (2007)
Photoreactivity of amino acids: tryptophan-induced photochemical events via reactive oxygen species generation.
Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 23, 943-948 [PubMed:17690425]
[show Abstract]
Tryptophan (Trp), an aromatic amino acid, is a constituent of peptides/proteins and is also a precursor of serotonin, kynurenine derivatives, and nicotinamide adenine dinucleotides. There have been a number of reports on photochemical reactions involving peptides/proteins which contain Trp that showed significant photodegradation, dimerization, and photoionization. The photochemical properties of Trp have not been fully elucidated, and this would provide novel insight into the handling of Trp-containing peptides/proteins. Consequently, we have been trying to evaluate the photochemical properties of Trp, as well as other essential amino acids, focusing on their photosensitivity, photodegradation, and their ability to induce lipid peroxidation. Among all the essential amino acids tested, Trp exhibited the maximal level of superoxide anion generation under 18 h of light exposure (30000 lux). UV spectral analysis of Trp suggested the absorbability of UVA/B light, and exposure of Trp, in both solid and solution states, to UVA/B light resulted in significant photodegradation (t(0.5): 18 h) and gradual color changes. In addition, photoirradiated Trp generated lipoperoxidant, a causative agent of photoirritation, and this might be associated with ROS generation. | Penberthy WT (2007)
Pharmacological targeting of IDO-mediated tolerance for treating autoimmune disease.
Current drug metabolism 8, 245-266 [PubMed:17430113]
[show Abstract]
Cells at the maternal-fetal interface express indoleamine 2,3 dioxygenase (IDO) to consume all local tryptophan for the express purpose of starving adjacent maternal T cells of this most limiting and essential amino acid. This stops local T cell proliferation to ultimately result in the most dramatic example of immune tolerance, acceptance of the fetus. By contrast, inhibition of IDO using 1-methyl-tryptophan causes a sudden catastrophic rejection of the mammalian fetus. Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells. Thus it makes sense to consider IDO induction towards tolerance for autoimmune diseases in general. Approaches to cell specific therapeutic IDO induction with NAD precursor supplementation to prevent the collateral non-T cell pathogenesis due to chronic TNFalpha-IDO activated tryptophan depletion in autoimmune diseases are reviewed. Tryptophan is an essential amino acid most immediately because it is the only precursor for the endogenous biosynthesis of nicotinamide adenine dinucleotide (NAD). Both autoimmune disease and the NAD deficiency disease pellagra occur in women at greater than twice the frequency of occurrence in men. The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2. Loss of function leads to psychotic symptoms rapidly progressing to presenile dementia likely due to unchecked increases in microglial IDO expression, which depletes neurons of tryptophan causing neurodegeneration. Administration of NAD precursors rescued entire mental hospitals of dementia patients literally overnight in the 1930's and NAD precursors should help Nasu-Hakola patients as well. NAD depletion mediated by peroxynitrate PARP1 activation is one of the few established mechanisms of necrosis. Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD. Pharmacological doses of NAD precursors repeatedly provide dramatic therapeutic benefit for rheumatoid arthritis, type 1 diabetes, multiple sclerosis, colitis, other autoimmune diseases, and schizophrenia in either the clinic or animal models. Collectively these observations support the idea that autoimmune disease may in part be considered as localized pellagra manifesting symptoms particular to the inflamed target tissues. Thus pharmacological doses of NAD precursors (nicotinic acid/niacin, nicotinamide/niacinamide, or nicotinamide riboside) should be considered as potentially essential to the therapeutic success of any IDO-inducing regimen for treating autoimmune diseases. Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic prostaglandins PGE(2) and PGD(2). Next, PGD(2) is converted to the anti-inflammatory prostaglandin, 15d-PGJ(2). These prostaglandins exert potent anti-inflammatory activities through endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma respectively. Nicotinamide prevents type 1 diabetes and ameliorates multiple sclerosis in animal models, while nothing is known about the therapeutic potential of nicotinamide riboside. Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration. | Raju TN, Kanth VR, Reddy PU (2007)
Influence of kynurenines in pathogenesis of cataract formation in tryptophan-deficient regimen in Wistar rats.
Indian journal of experimental biology 45, 543-548 [PubMed:17585690]
[show Abstract]
L-Tryptophan (Trp) is an essential amino acid and its deficiency is involved in various pathologies. In this present investigation an attempt was made to study the role of tryptophan and its metabolites in cataract formation in wistar rats. Rats were divided and maintained in 3 groups, Group A--control; Group B--marginal-tryptophan and Group C--Tryptophan-deficient diet for 3 months. Slit lamp microscope observations indicated lenticular opacities in Group-C (tryptophan-deficient) rats. In the rats that were maintained on tryptophan deficient diet, a decrease in protein content, kynurenines, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-tranferase (GSTs) and tryptophan-fluorescence intensities and an increase in lipid peroxidation indicative of oxidative stress have been observed. The above changes were normalized in the rats on supplementation of 0.05% tryptophan (Group-B) in their diets. These results suggest that tryptophan-deficiency in the diet leads to an overall significant decrease in kynurenines and levels of antioxidant enzymes (except SOD) in ocular tissue with a concomitant lenticular opacification. The results suggest that diet with adequate tryptophan has protective influence and is of immense benefit in mitigating the changes that may otherwise contribute to the lenticular opacities. | Voracek M, Tran US (2007)
Dietary tryptophan intake and suicide rate in industrialized nations.
Journal of affective disorders 98, 259-262 [PubMed:16934873]
[show Abstract]
BackgroundThe objective of this study was to assess the ecological association of dietary tryptophan intake and suicide rates across industrialized nations. Tryptophan, an essential amino acid, is the rate-limiting precursor of serotonin biosynthesis. The serotonergic system has been strongly implicated in the neurobiology of suicide.MethodsContemporary male and female suicide rates for the general population (42 countries) and the elderly (38 countries) were correlated with national estimates of dietary tryptophan intake.ResultsMeasures of tryptophan intake were significantly negatively associated to national suicide rates. Controlling for national affluence, total alcohol consumption and happiness levels slightly attenuated these associations, but left all of them negative.LimitationsThe effect is an ecological (group-level) finding. Estimated per capita tryptophan supply is only a proxy for actual consumption.ConclusionsDeveloped nations ranking high in dietary tryptophan intake rank low in suicide rates, independent of national wealth, alcohol intake and happiness. | Bosch L, Alegría A, Farré R (2006)
Amino acid contents of infant foods.
International journal of food sciences and nutrition 57, 212-218 [PubMed:17127472]
[show Abstract]
The protein quality of three milk-cereal-based infant foods (paps) was evaluated by determining their amino acid contents and calculating the amino acid score. Proteins were subjected to acid hydrolysis, prior to which cysteine and methionine were oxidized with performic acid. Amino acids were determined by reverse-phase high-performance liquid chromatography with fluorescence detection with a prior derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. Tryptophan was determined by reverse-phase high-performance liquid chromatography with ultraviolet detection after basic hydrolysis. Glutamic acid, proline and leucine were the most abundant amino acids, whereas tryptophan and cysteine had the lowest contents. Tryptophan was the limiting amino acid in the analyzed infant foods. A pap serving (250 ml) contributes significantly to fulfillment of the recommended dietary allowances of essential and semi-essential amino acids for infants (7-12 months old) and young children (1-3 years old). | Pazos M, Andersen ML, Skibsted LH (2006)
Amino acid and protein scavenging of radicals generated by iron/hydroperoxide system: an electron spin resonance spin trapping study.
Journal of agricultural and food chemistry 54, 10215-10221 [PubMed:17177562]
[show Abstract]
Reduction of free radicals generated by Fe(II)/cumene-hydroperoxide (CumOOH) by amino acids (Gly, Cys, Met, His, and Trp) and proteins (bovine serum albumin (BSA), beta-lactoglobulin, and lactoferrin) was followed by electron spin resonance spectroscopy using alpha-phenyl-N-tert-butylnitrone (PBN), 2-methyl-2-nitrosopropane (MNP), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as spin traps. The radical species detected were mostly carbon-centered radicals from CumOOH fragmentation (methyl/*H3 and ethyl/*H2CH3), although carbon-centered radicals originated from amino acids could be formed in the presence of Cys, Met, His, or Trp. All proteins and amino acids, except Cys, were effective at inhibiting generation of radicals from the Fe(II)/CumOOH system. Trp was the amino acid with the highest antiradical activity, followed by His > Gly approximately Met. Lactoferrin was the protein showing the most efficient inhibition of radical formation from the Fe(II)/CumOOH system, and BSA and beta-lactoglobulin were not significantly different in their antiradical activities. These results suggest that proteins with higher inhibitory activity on lipid oxidation promoted by transition metal catalytic decomposition of hydroperoxides should be those with elevated metal-chelating and radical-scavenging properties as well as low concentration and accessibility of reducing groups from amino acids capable of activating metals, such as sulfhydryl groups. | Akers JC, Tan M (2006)
Molecular mechanism of tryptophan-dependent transcriptional regulation in Chlamydia trachomatis.
Journal of bacteriology 188, 4236-4243 [PubMed:16740930]
[show Abstract]
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 regulates its own gene and trpB and trpA, the genes for the two subunits of tryptophan synthase. These three genes form an operon that is transcribed by the major form of chlamydial RNA polymerase. TrpR acts as a tryptophan-dependent aporepressor that binds specifically to operator sequences upstream of the trpRBA operon. We also found that TrpR repressed in vitro transcription of trpRBA in a promoter-specific manner, and the level of repression was dependent upon the concentrations of TrpR and tryptophan. Our findings provide a mechanism for chlamydiae to sense changes in tryptophan levels and to respond by modulating expression of the tryptophan biosynthesis genes, and we present a unified model that shows how C. trachomatis can combine transcriptional repression and attenuation to regulate intrachlamydial tryptophan levels. In the face of host defense mechanisms that limit tryptophan availability from the infected cell, the ability to maintain homeostatic control of intrachlamydial tryptophan levels is likely to play an important role in chlamydial pathogenesis. | Melchior D, Le Floc'h N, Sève B (2003)
Effects of chronic lung inflammation on tryptophan metabolism in piglets.
Advances in experimental medicine and biology 527, 359-362 [PubMed:15206750]
[show Abstract]
A fundamental question in animal nutrition is the amino acid requirement induced by inflammation and immune response. The aim of the present experiment was to study the effect of chronic lung inflammation induced by injection of complete Freund adjuvant on amino acid metabolism in pigs. For 10 days, we compared plasma haptoglobine and amino acid concentrations of piglets with chronic lung inflammation (CFA) with those of pair-fed littermate healthy pigs (CONTROL). Tryptophan was the only amino acid for which the plasma concentration was continously decreasing and did not reach the control level at the end of the experimental period. We suggested that an increase in tryptophan catabolism under indoleamine 2, 3 dioxygenase activation and/or tryptophan incorporation into acute phase protein could explained the decrease in plasma tryptophan concentration in pigs suffuring from chronic lung inflammation. | Wirleitner B, Neurauter G, Schröcksnadel K, Frick B, Fuchs D (2003)
Interferon-gamma-induced conversion of tryptophan: immunologic and neuropsychiatric aspects.
Current medicinal chemistry 10, 1581-1591 [PubMed:12871129]
[show Abstract]
Tryptophan is an essential amino acid and the least abundant constituent of proteins. In parallel it represents a source for two important biochemical pathways: the generation of neurotransmitter 5-hydroxytryptamine (serotonin) by the tetrahydrobiopterin-dependent tryptophan 5-hydroxylase, and the formation of kynurenine derivatives and nicotinamide adenine dinucleotides initiated by the enzymes tryptophan pyrrolase (tryptophan 2,3-dioxygenase, TDO) and indoleamine 2,3-dioxygenase (IDO). Whereas TDO is located in the liver cells, IDO is expressed in a large variety of cells and is inducible by the cytokine interferon-gamma. Therefore, accelerated tryptophan degradation is observed in diseases and disorders concomitant with cellular immune activation, e. g. infectious, autoimmune, and malignant diseases, as well as during pregnancy. According to the cytostatic and antiproliferative properties of tryptophan-depletion on T lymphocytes, activated T-helper type 1 (Th-1) cells may down-regulate immune response via degradation of tryptophan. Especially in states of persistent immune activation availability of free serum tryptophan is diminished and as a consequence of reduced serotonin production, serotonergic functions may as well be affected. Accumulation of neuroactive kynurenine metabolites such as quinolinic acid may contribute to the development of neurologic/psychiatric disorders. Thus, IDO seems to represent a link between the immunological network and neuroendocrine functions with far reaching consequences in regard to the psychological status of patients. These observations provide a basis for the better understanding of mood disorder and related symptoms in chronic diseases. | Littlejohn TK, Takikawa O, Truscott RJ, Walker MJ (2003)
Asp274 and his346 are essential for heme binding and catalytic function of human indoleamine 2,3-dioxygenase.
The Journal of biological chemistry 278, 29525-29531 [PubMed:12766158]
[show Abstract]
L-Tryptophan is the least abundant essential amino acid in humans. Indoleamine 2,3-dioxgyenase (IDO) is a cytosolic heme protein which, together with the hepatic enzyme tryptophan 2,3-dioxygenase, catalyzes the first and rate-limiting step in the major pathway of tryptophan metabolism, the kynurenine pathway. The physiological role of IDO is not fully understood but is of great interest, because IDO is widely distributed in human tissues, can be up-regulated via cytokines such as interferon-gamma, and can thereby modulate the levels of tryptophan, which is vital for cell growth. To identify which amino acid residues are important in substrate or heme binding in IDO, site-directed mutagenesis of conserved residues in the IDO gene was undertaken. Because it had been proposed that a histidine residue might be the proximal heme ligand in IDO, mutation to alanine of the three highly conserved histidines His16, His303, and His346 was conducted. Of these, only His346 was shown to be essential for heme binding, indicating that this histidine residue may be the proximal ligand and suggesting that neither His303 nor His16 act as the proximal ligand. Site-directed mutagenesis of Asp274 also compromised the ability of IDO to bind heme. This observation indicates that Asp274 may coordinate to heme directly as the distal ligand or is essential in maintaining the conformation of the heme pocket. | Young SN, Leyton M (2002)
The role of serotonin in human mood and social interaction. Insight from altered tryptophan levels.
Pharmacology, biochemistry, and behavior 71, 857-865 [PubMed:11888576]
[show Abstract]
Alterations in brain tryptophan levels cause changes in brain serotonin synthesis, and this has been used to study the implication of altered serotonin levels in humans. In the acute tryptophan depletion (ATD) technique, subjects ingest a mixture of amino acids devoid of tryptophan. This results in a transient decline in tissue tryptophan and in brain serotonin. ATD can result in lower mood and increase in irritability or aggressive responding. The magnitude of the effect varies greatly depending on the susceptibility of the subject to lowered mood or aggressivity. Unlike ATD, tryptophan can be given chronically. Tryptophan is an antidepressant in mild to moderate depression and a small body of data suggests that it can also decrease aggression. Preliminary data indicate that tryptophan also increases dominant behavior during social interactions. Overall, studies manipulating tryptophan levels support the idea that low serotonin can predispose subjects to mood and impulse control disorders. Higher levels of serotonin may help to promote more constructive social interactions by decreasing aggression and increasing dominance. | Azmitia EC (2001)
Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis.
Brain research bulletin 56, 413-424 [PubMed:11750787]
[show Abstract]
Evolutionarily, serotonin existed in plants even before the appearance of animals. Indeed, serotonin may be tied to the evolution of life itself, particularly through the role of tryptophan, its precursor molecule. Tryptophan is an indole-based, essential amino acid which is unique in its light-absorbing properties. In plants, tryptophan-based compounds capture light energy for use in metabolism of glucose and the generation of oxygen and reduced cofactors. Tryptophan, oxygen, and reduced cofactors combine to form serotonin. Serotonin-like molecules direct the growth of light-capturing structures towards the source of light. This morphogenic property also occurs in animal cells, in which serotonin alters the cytoskeleton of cells and thus influences the formation of contacts. In addition, serotonin regulates cell proliferation, migration and maturation in a variety of cell types, including lung, kidney, endothelial cells, mast cells, neurons and astrocytes). In brain, serotonin has interactions with seven families of receptors, numbering at least 14 distinct proteins. Of these, two receptors are important for the purposes of this review. These are the 5-HT1A and 5-HT2A receptors, which in fact have opposing functions in a variety of cellular and behavioral processes. The 5-HT1A receptor develops early in the CNS and is associated with secretion of S-100beta from astrocytes and reduction of c-AMP levels in neurons. These actions provide intracellular stability for the cytoskeleton and result in cell differentiation and cessation of proliferation. Clinically, 5-HT1A receptor drugs decrease brain activity and act as anxiolytics. The 5-HT2A receptor develops more slowly and is associated with glycogenolysis in astrocytes and increased Ca(++) availability in neurons. These actions destabilize the internal cytoskeleton and result in cell proliferation, synaptogenesis, and apoptosis. In humans, 5-HT2A receptor drugs produce hallucinations. The dynamic interactions between the 5-HT1A and 5-HT2A receptors and the cytoskeleton may provide important insights into the etiology of brain disorders and provide novel strategies for their treatment. | Gosset G, Bonner CA, Jensen RA (2001)
Microbial origin of plant-type 2-keto-3-deoxy-D-arabino-heptulosonate 7-phosphate synthases, exemplified by the chorismate- and tryptophan-regulated enzyme from Xanthomonas campestris.
Journal of bacteriology 183, 4061-4070 [PubMed:11395471]
[show Abstract]
Enzymes performing the initial reaction of aromatic amino acid biosynthesis, 2-keto-3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthases, exist as two distinct homology classes. The three classic Escherichia coli paralogs are AroA(I) proteins, but many members of the Bacteria possess the AroA(II) class of enzyme, sometimes in combination with AroA(I) proteins. AroA(II) DAHP synthases until now have been shown to be specifically dedicated to secondary metabolism (e.g., formation of ansamycin antibiotics or phenazine pigment). In contrast, here we show that the Xanthomonas campestris AroA(II) protein functions as the sole DAHP synthase supporting aromatic amino acid biosynthesis. X. campestris AroA(II) was cloned in E. coli by functional complementation, and genes corresponding to two possible translation starts were expressed. We developed a 1-day partial purification method (>99%) for the unstable protein. The recombinant AroA(II) protein was found to be subject to an allosteric pattern of sequential feedback inhibition in which chorismate is the prime allosteric effector. L-Tryptophan was found to be a minor feedback inhibitor. An N-terminal region of 111 amino acids may be located in the periplasm since a probable inner membrane-spanning region is predicted. Unlike chloroplast-localized AroA(II) of higher plants, X. campestris AroA(II) was not hysteretically activated by dithiols. Compared to plant AroA(II) proteins, differences in divalent metal activation were also observed. Phylogenetic tree analysis shows that AroA(II) originated within the Bacteria domain, and it seems probable that higher-plant plastids acquired AroA(II) from a gram-negative bacterium via endosymbiosis. The X. campestris AroA(II) protein is suggested to exemplify a case of analog displacement whereby an ancestral aroA(I) species was discarded, with the aroA(II) replacement providing an alternative pattern of allosteric control. Three subgroups of AroA(II) proteins can be recognized: a large, central group containing the plant enzymes and that from X. campestris, one defined by a three-residue deletion near the conserved KPRS motif, and one possessing a larger deletion further downstream. | Hayase F, Nagaraj RH, Miyata S, Njoroge FG, Monnier VM (1989)
Aging of proteins: immunological detection of a glucose-derived pyrrole formed during maillard reaction in vivo.
The Journal of biological chemistry 264, 3758-3764 [PubMed:2917974]
[show Abstract]
Recent work from this laboratory revealed that glucose-derived pyrroles can form with model amines under physiological conditions (Niroge, F. G., Sayre, L. M., and Monnier, V. M. (1987) Carbohydr. Res. 167, 211-220). The major extractable product, 5-hydroxymethyl-1-alkylpyrrole-2-carbaldehyde (named by us pyrraline) was labile to acid hydrolysis. To allow its detection in proteins undergoing advanced glycosylation, an enzyme-linked immunosorbent assay was developed. An immunogen consisting of epsilon-caproyl pyrraline (hapten) was linked onto poly-L-lysine (114:1) and used to raise polyclonal antibodies in the rabbit. High antibody titers were obtained 16 weeks after immunization. The antibody cross-reacted with butyl pyrraline (88%), propyl pyrraline (8%), lysyl pyrraline (2%), and neopentyl pyrraline (1.3%). A time-related increase in pyrraline immunoreactivity was observed in bovine serum albumin incubated with glucose (1000 mM), glycated lysine (50 mM), and 3-deoxyglucosone (50 mM) which reached 25, 300, and 350 pmol/mg, respectively, after 30 days. Mean level of protein pyrraline immunoreactivity were 27.0 +/- 7.2 and 43.3 +/- 11.7 pmol/mg in serum albumin from control and diabetic subjects, respectively (p less than 0.001). The pathobiological relevance of pyrraline may relate to its reported antiproteolytic and mutagenic properties. In addition, glucose-derived pyrroles may play a role in diabetic neuropathy in analogy to pyrroles formed during hexane-induced neuropathy. | National Toxicology Program (1978)
Bioassay of L-Tryptophan for Possible Carcinogenicity (CAS No. 73-22-3).
National Cancer Institute carcinogenesis technical report series 71, 1-115 [PubMed:12830226]
[show Abstract]
L-Tryptophan is an essential amino acid for humans, and a precursor of the neurohormones serotonin (5-hydroxytryptamine) and melatonin (N-acetyl-5-methoxytryptamine), and the B vitamin nicotinic acid. It is found in small concentrations in casein, and in many foods. A bioassay of the amino acid L-tryptophan for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice. Groups of 35 rats and 35 mice of each sex were administered L-tryptophan at one of two doses, either 25,000 or 50,000 ppm, 5 days per week for 78 weeks, and then observed for 26 or 27 weeks. Matched controls consisted of groups of 15 rats or 15 mice of each sex. All surviving rats and mice were killed at 104 or 105 weeks. L-Tryptophan had little toxic effect on the rats; mean body weight loss was minimal and survival of dosed groups of both sexes was high. In the mice, mean body weights of dosed animals were lower than those of controls throughout most of the bioassay, particularly in the females. Sufficient numbers of rats were at risk to termination of the study for development of late-appearing tumors, and sufficient numbers of mice were at risk beyond 52 weeks of the study for development of tumors. No neoplasms occurred in a statistically significant incidence among dosed rats when compared with controls. In both male and female mice, neoplasms of the hematopoietic system occurred at higher incidences in the low-dose groups than in the matched-control groups (males: controls 0/12, low-dose 9/34, high-dose 2/33; females: controls 2/13, low-dose 6/33, high-dose 1/35). These incidences, however, are not statistically significant, using the Bonferroni correction, and therefore, no tumors are considered to be related to the administration of the test chemical. It is concluded that under the conditions of this bioassay, L-tryptophan was not carcinogenic for Fischer 344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative Synonym: L-a |
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