Role Of Tryptophan Research Articles

Characterization of a Novel Monoclonal Antibody with High Affinity and Specificity against Aflatoxins: A Discovery from Rosetta Antibody-Ligand Computational Simulation.

Aflatoxin B1 (AFB1) accumulates in crops, where it poses a threat to human health. To detect AFB1, anti-AFB1 monoclonal antibodies have been developed and are widely used. While the sensitivity and specificity of these antibodies have been extensively studied, information regarding the atomic-level docking of AFB1 (and its derivatives) with these antibodies is limited. Such information is crucial for understanding the key interactions that are required for high affinity and specificity in aflatoxin binding. First, a 3D comparative model of anti-AFB1 antibody (Ab-4B5G6) was predicted from the sequence using RosettaAntibody. We then utilized RosettaLigand to dock AFB1 onto ten homology models, producing a total of 10,000 binding modes. Interestingly, the best-scoring mode predicted strong interactions involving four sites within the heavy chain: ALA33, ASN52, HIS95, and TRP99. Importantly, these strong binding interactions exclusively involve the variable domain of the heavy chain. The best-scoring mode with AFB1 was also obtained through AF multimer combined with RosettaLigand, and two interactions at TRP and HIS were consistent with those found by Rosetta antibody-ligand computational simulation. The role of tryptophan in π interactions in antibodies was confirmed through mutation experiments, and the resulting mutant (W99A) exhibited a >1000-fold reduction in binding affinity for AFB1 and analogs, indicating the effect of tryptophan on the stability of CDR-H3 region. Additionally, we evaluated the binding of two glycolic acid-derived molecular derivatives (with impaired hydrogen bonding potential), and these derivatives (AFB2-GA and AFG2-GA) demonstrated a very weak binding affinity for Ab-4B5G6. The heavy chain was successfully isolated, and its sensitivity and specificity were consistent with those of the intact antibody. The homology models of variable heavy (VH) single-domain antibodies were established by RosettaAntibody, and the docking analysis revealed the same residues, including Ala, His, and Trp. Compared to the potential binding mode of fragment variable (FV) region, the results from a model of VH indicated that there are seven models involved in hydrophobic interaction with TYR32, which is usually referred to as polar amino acid and has both hydrophobic and hydrophilic features depending on the circumstances. Our work encompasses the entire process of Rosetta antibody-ligand computational simulation, highlighting the significance of variable heavy domain structural design in enhancing molecular interactions.

Comprehensive multi-omics analysis of tryptophan metabolism-related gene expression signature to predict prognosis in gastric cancer.

Introduction: The 5-year survival of gastric cancer (GC) patients with advanced stage remains poor. Some evidence has indicated that tryptophan metabolism may induce cancer progression through immunosuppressive responses and promote the malignancy of cancer cells. The role of tryptophan and its metabolism should be explored for an in-depth understanding of molecular mechanisms during GC development. Material and methods: We utilized the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to screen tryptophan metabolism-associated genes via single sample gene set enrichment analysis (ssGSEA) and correlation analysis. Consensus clustering analysis was employed to construct different molecular subtypes. Most common differentially expressed genes (DEGs) were determined from the molecular subtypes. Univariate cox analysis as well as lasso were performed to establish a tryptophan metabolism-associated gene signature. Gene Set Enrichment Analysis (GSEA) was utilized to evaluate signaling pathways. ESTIMATE, ssGSEA, and TIDE were used for the evaluation of the gastric tumor microenvironment. Results: Two tryptophan metabolism-associated gene molecular subtypes were constructed. Compared to the C2 subtype, the C1 subtype showed better prognosis with increased CD4 positive memory T cells as well as activated dendritic cells (DCs) infiltration and suppressed M2-phenotype macrophages inside the tumor microenvironment. The immune checkpoint was downregulated in the C1 subtype. A total of eight key genes, EFNA3, GPX3, RGS2, CXCR4, SGCE, ADH4, CST2, and GPC3, were screened for the establishment of a prognostic risk model. Conclusion: This study concluded that the tryptophan metabolism-associated genes can be applied in GC prognostic prediction. The risk model established in the current study was highly accurate in GC survival prediction.

Improvement of flesh quality, muscle growth and protein deposition in adult grass carp (Ctenopharyngodon idella): The role of tryptophan

The muscle is the main edible part of the animal trunk. Previous studies have shown that tryptophan is the limiting amino acid for protein synthesis. This study investigated whether dietary tryptophan could improve growth performance, flesh quality, muscle growth, and protein deposition in adult grass carp (Ctenopharyngodon idella). 450 grass carp (671.31 ± 1.66 g) were fed with six diets (iso‑nitrogenous) with different concentrations of tryptophan (0.25, 1.66, 3.12, 4.69, 5.95, and 7.61 g/kg diet) for 9 weeks. The results revealed that the optimal tryptophan levels (3.12 or 4.69 g/kg diet) increased feed intake (FI), feed efficiency (FE), percent weight gain (PWG), and specific growth rate (SGR) compared with the deficient group (0.25 g/kg diet), indicating that tryptophan improved the growth performance of adult grass carp. The optimal tryptophan levels increased the muscle contents of protein, lipid, protein-bound amino acids, free amino acids (FAA), pH24h, and shear force; improved the fatty acid (FA) profile in muscle; and reduced cooking loss and lactate content, suggesting that tryptophan improved the flesh quality of adult grass carp. The optimal tryptophan levels increased the myofiber diameter, frequency of >50 μm diameter fiber, mRNA levels of MRFs (MyoD, MyoG, Mrf4, and Myf5), and decreased the mRNA levels of MSTN in muscle, indicating that tryptophan promoted muscle growth in adult grass carp. We further found that the promotion of muscle protein deposition by dietary tryptophan may be related to protein synthesis, ubiquitin-proteasome, and autophagic lysosomal pathways. We discovered that dietary tryptophan increased the mRNA abundances of IGF-1, PI3K, AKT, TOR, and S6K1 and decreased the mRNA abundances of 4EBP1, FOXO1a, FOXO3a, MAFBX, MuRF1, UB, ULK1, Beclin1, ATG5, ATG12, p62, LC3–1, and LC3–2, thereby promoting muscle protein deposition in adult grass carp. The above results showed that dietary tryptophan enhanced growth performance, flesh quality, muscle growth, and muscle protein deposition in adult grass carp. Moreover, using broken line regression, the tryptophan requirement of adult grass carp was estimated to be 3.02 g/kg diet (11.64 g/kg protein) based on PWG.

Tryptophan and Substance Abuse: Mechanisms and Impact.

Addiction, the continuous misuse of addictive material, causes long-term dysfunction in the neurological system. It substantially affects the control strength of reward, memory, and motivation. Addictive substances (alcohol, marijuana, caffeine, heroin, methamphetamine (METH), and nicotine) are highly active central nervous stimulants. Addiction leads to severe health issues, including cardiovascular diseases, serious infections, and pulmonary/dental diseases. Drug dependence may result in unfavorable cognitive impairments that can continue during abstinence and negatively influence recovery performance. Although addiction is a critical global health challenge with numerous consequences and complications, currently, there are no efficient options for treating drug addiction, particularly METH. Currently, novel treatment approaches such as psychological contingency management, cognitive behavioral therapy, and motivational enhancement strategies are of great interest. Herein, we evaluate the devastating impacts of different addictive substances/drugs on users' mental health and the role of tryptophan in alleviating unfavorable side effects. The tryptophan metabolites in the mammalian brain and their potential to treat compulsive abuse of addictive substances are investigated by assessing the functional effects of addictive substances on tryptophan. Future perspectives on developing promising modalities to treat addiction and the role of tryptophan and its metabolites to alleviate drug dependency are discussed.

Roles of Tryptophan and Charged Residues on the Polymorphisms of Amyloids Formed by K-Peptides of Hen Egg White Lysozyme Investigated through Molecular Dynamics Simulations.

Atomistic molecular dynamics simulations of amyloid models, consisting of the previously reported STDY-K-peptides and K-peptides from the hen egg white lysozyme (HEWL), were performed to address the effects of charged residues and pH observed in an in vitro study. Simulation results showed that amyloid models with antiparallel configurations possessed greater stability and compactness than those with parallel configurations. Then, peptide chain stretching and ordering were measured through the end-to-end distance and the order parameter, for which the amyloid models consisting of K-peptides and the STDY-K-peptides at pH 2 displayed a higher level of chain stretching and ordering. After that, the molecular mechanics energy decomposition and the radial distribution function (RDF) clearly displayed the importance of Trp62 to the K-peptide and the STDY-K-peptide models at pH 2. Moreover, the results also displayed how the negatively charged Asp52 disrupted the interaction networks and prevented the amyloid formation from STDY-K-peptide at pH 7. Finally, this study provided an insight into the interplay between pH conditions and molecular interactions underlying the formation of amyloid fibrils from short peptides contained within the HEWL. This served as a basis of understanding towards the design of other amyloids for biomaterial applications.

Obez hastalarda serum leptin ve triptofan düzeylerinin depresyon ve anksiyete ile ilişkisi var mı?

Objectives: Depression and anxiety are common conditions in obese patients. Leptin plays a role in obesity, the role of tryptophan in obesity has been investigated frequently in current studies. The aim of this study is to evaluate whether serum leptin and triptophan levels are related to depression and anxiety in obesity patients. Methods: This is a descriptive and cross-sectional study in which the data of 88 patients aged 18 years and over, BMI 25 kg/m2 and above, who applied to the Family Medicine outpatient clinic between 01.07.2019 and 31.12.2019, were examined. Sociodemographic data form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) were completed by all patients included in the study. Results: There was no significant relationship between BMI and leptin, BMI and tryptophan levels. A positive correlation was found between tryptophan and weight, waist circumference and systolic blood pressure (SBP). Tryptophan was also significantly higher in smokers and those with a history of psychiatric treatment. Tryptophan levels in men were found to be significantly higher than in women. Serum tryptophan concentration of the patients was positively correlated with weight, waist circumference and SBP. Tryptophan level was found significantly higher in men than in women. Tryptophan was also significantly higher in smokers and those with a history of psychiatric treatment. There was no significant relationship between BDI, BAI and leptin and tryptophan levels. Conclusion: The significant relationships between serum tryptophan level and weight, waist circumference and SBP may be useful in the management, follow-up and treatment of obese patients.

The role of tryptophan in Chlamydia trachomatis persistence.

Chlamydia trachomatis (C. trachomatis) is the most common etiological agent of bacterial sexually transmitted infections (STIs) and a worldwide public health issue. The natural course with C. trachomatis infection varies widely between individuals. Some infections clear spontaneously, others can last for several months or some individuals can become reinfected, leading to severe pathological damage. Importantly, the underlying mechanisms of C. trachomatis infection are not fully understood. C. trachomatis has the ability to adapt to immune response and persist within host epithelial cells. Indoleamine-2,3-dioxygenase (IDO) induced by interferon-gamma (IFN-γ) degrades the intracellular tryptophan pool, to which C. trachomatis can respond by converting to a non-replicating but viable state. C. trachomatis expresses and encodes for the tryptophan synthase (TS) genes (trpA and trpB) and tryptophan repressor gene (trpR). Multiple genes interact to regulate tryptophan synthesis from exogenous indole, and persistent C. trachomatis can recover its infectivity by converting indole into tryptophan. In this review, we discuss the characteristics of chlamydial infections, biosynthesis and regulation of tryptophan, the relationship between tryptophan and C. trachomatis, and finally, the links between the tryptophan/IFN-γ axis and C. trachomatis persistence.

The Role of Tryptophan in π Interactions in Proteins: An Experimental Approach.

In proteins, the amino acids Phe, Tyr, and especially Trp are frequently involved in π interactions such as π–π, cation−π, and CH−π bonds. These interactions are often crucial for protein structure and protein–ligand binding. A powerful means to study these interactions is progressive fluorination of these aromatic residues to modulate the electrostatic component of the interaction. However, to date no protein expression platform is available to produce milligram amounts of proteins labeled with such fluorinated amino acids. Here, we present a Lactococcus lactis Trp auxotroph-based expression system for efficient incorporation (≥95%) of mono-, di-, tri-, and tetrafluorinated, as well as a methylated Trp analog. As a model protein we have chosen LmrR, a dimeric multidrug transcriptional repressor protein from L. lactis. LmrR binds aromatic drugs, like daunomycin and riboflavin, between Trp96 and Trp96′ in the dimer interface. Progressive fluorination of Trp96 decreased the affinity for the drugs 6- to 70-fold, clearly establishing the importance of electrostatic π–π interactions for drug binding. Presteady state kinetic data of the LmrR–drug interaction support the enthalpic nature of the interaction, while high resolution crystal structures of the labeled protein–drug complexes provide for the first time a structural view of the progressive fluorination approach. The L. lactis expression system was also used to study the role of Trp68 in the binding of riboflavin by the membrane-bound riboflavin transport protein RibU from L. lactis. Progressive fluorination of Trp68 revealed a strong electrostatic component that contributed 15–20% to the total riboflavin-RibU binding energy.

How Decreased Level of Plasma Tryptophan Play Role in Diabetic Patients?

Tryptophan is an essential amino acid found in many protein-based foods and dietary proteins including meats, dairy, fruits, and seeds. High-glycaemic index and -glycaemic load meals also increase the availability of tryptophan. The main objective of the study is to find the role of tryptophan in diabetic patients. Tryptophan metabolism has been reported highly associated with insulin resistance and diabetes risk. The activity of rate-limiting enzyme of tryptophan-kynurenine, indoleamine-2,3-dioxygenase (IDO), was enhanced significantly in T2D patients, thus downstream metabolites such as kynurenine, kynurenic acid, xanthurenic acid and hydroxykynurenine, were higher in T2D than in non-diabetic subjects, although inconsistent observations of tryptophan levels. Returning to the question posed at the beginning of the review, these studies have shown that decreased level of tryptophan plays an important role in diabetic patients. decrease in plasma TRP levels in diabetic patients regardless of their gender and these patients also exhibited a greater incidence of memory dysfunction compared to the controls.

Melatonin treatment of delirious state: A case study

Melatonin secretion decreases with age and in neurodegenerative diseases like Alzheimer’s Disease (AD). Sundown syndrome (“sundowning”), characterized by agitation, wandering, anxiety, aggression and confusion in the evening and at night is prevalent among demented patients [1,2]. Delirious state is a very common complication in severe dementia, dysregulation of the sleep-wake cycle is one characteristic finding during delirium. Melatonin is able to correct this circadian rhythm disorder [1,3]. Dysfunction of noradrenergic regulation and low tryptophan levels were found to be associated with delirium in the elderly, supporting the hypothesis of a possible role of tryptophan or tryptophan-like compounds such as melatonin in the pathogenesis of delirium [1,4].

Investigation of possible associations between tryptophan/kynurenine status and FOXP3 expression in colorectal cancer

Tryptophan metabolism in the tumor microenvironment exerts immunosuppressive effects by affecting the anti-tumor functions of immune cells. The immunosuppressive roles of tryptophan and tryptophan metabolites and their effects on the FOXP3 gene, highly expressed in regulatory T cells (Tregs), are remarkable. Our study aimed to investigate the relation between tryptophan metabolism and the transcription factor FOXP3 gene in colorectal cancer (CRC). Patients with CRC (n = 159) and controls (n = 112) were included in the study. The FOXP3 rs3761548 variant genotyping from the isolated genomic DNA was performed by PCR-RFLP. FOXP3 gene expression was determined by Q-PCR in RNAs isolated from resected tissues at the same time. Serum tryptophan, kynurenine, kynurenic acid levels of the cases were determined by HPLC. In serum samples with CRC, tryptophan level was 14.32 ± 1.09 μmol/L, kynurenine level was 1.33 ± 0.02 μmol/L, and the kynurenic acid level was 0.01 ± 0.001 μmol/L. The level of tryptophan was found to be low in CRC compared to control (p < .001). In cases with CRC, CC genotype (p = .048) and C allele (p = .012) frequency for FOXP3 rs3761548 were higher than the control group. It was found that the expression level of the FOXP3 gene was approximately 44 times higher in the advanced tumor stage (T3 + T4) than in the early tumor stage (T1 + T2) (p = .021). We suggest that there may be a possible relationship among serum TRP, TRP metabolites (KYN, KYNA) levels, FOXP3 gene expression, and FOXP3 gene variants in CRC pathogenesis.

UV radiation damage of human gamma D crystallin: role of tryptophans

Cataract is one of the main causes of blindness worldwide and is due to aggregation of eye lens proteins. Age, UV radiation, oxidation, metal ions, deamidation, and truncations are factor risks that cause protein damage and induce aggregation. Human γD (HgD) crystallin is one of the most abundant crystallins in the lens nucleus and its non-amyloid aggregation is

Роль незаменимой аминокислоты триптофана в возникновении нарушений сна и тревожно-депрессивных расстройств

Sleep is one of the most important and vital physiological processes in the human body. In addition to the length of daylight hours, the nature of work activity, bad habits (smoking, alcohol abuse, excessive consumption of caffeine-containing drinks, psychostimulants), the factors that violate the duration and quality of sleep include the nature and style of nutrition, as well as eating habits that affect daily intake vital nutrients (vitamins, essential amino acids, polyunsaturated fatty acids, etc.). Tryptophan is one of the essential amino acids associated with sleep disturbance. Given the high clinical significance of sleep disorders in the development of neurological diseases and mental disorders, the interest of researchers in the study of modifiable and non-modifiable risk factors for sleep disorders is growing. Objective: to analyze and systematize the results of fundamental and clinical studies of recent years on the role of tryptophan in the development of sleep disorders and anxiety-depressive disorders in adults. Materials and methods. This thematic review included available full-text publications obtained as a result of a literary search in the domestic (E-Library) and foreign databases (PubMed, Scopus, Oxford University Press, Springer, Web of Science Core Collection). Results. The role of tryptophan as a key link in the synthesis of melatonin and serotonin in the occurrence of sleep disorders and anxiety-depressive disorders is significant and can be used for further study. Conclusion. Based on the review of the literature, it can be concluded that one of the important mechanisms of sleep disturbance and the occurrence of anxiety and depressive disorders is insufficient intake of tryptophan in the body. This pattern is a consequence of the consumption of food with a low content of this essential amino acid. Considering the consequences that tryptophan depletion can lead to in the human body, competent nutritional support is a necessary measure.

Intestinal Dysbiosis, the Tryptophan Pathway and Nonalcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH), which may then progress to the development of cirrhosis and hepatocarcinoma. NASH is characterized by both steatosis and inflammation. Control of inflammation in NASH is a key step for the prevention of disease progression to severe sequalae. Intestinal dysbiosis has been recognized to be an important causal factor in the pathogenesis of NASH, involving both the accumulation of lipids and aggravation of inflammation. The effects of gut dysbiosis are mediated by adverse shifts of various intestinal commensal bacterial genera and their associated metabolites such as butyrate, tryptophan, and bile acids. In this review, we focus on the roles of tryptophan and its metabolites in NASH in association with intestinal dysbiosis and discuss possible therapeutic implications.

Tryptophan plays an important role in yeast\u2019s tolerance to isobutanol

BackgroundIsobutanol is considered a potential biofuel, thanks to its high-energy content and octane value, limited water solubility, and compatibility with gasoline. As its biosynthesis pathway is known, a microorganism, such as Saccharomyces cerevisiae, that inherently produces isobutanol, can serve as a good engineering host. Isobutanol’s toxicity, however, is a major obstacle for bioproduction. This study is to understand how yeast tolerates isobutanol.ResultsA S. cerevisiae gene-deletion library with 5006 mutants was used to screen genes related to isobutanol tolerance. Image recognition was efficiently used for high-throughput screening via colony size on solid media. In enrichment analysis of the 161 isobutanol-sensitive clones identified, more genes than expected were mapped to tryptophan biosynthesis, ubiquitination, and the pentose phosphate pathway (PPP). Interestingly, adding exogenous tryptophan enabled both tryptophan biosynthesis and PPP mutant strains to overcome the stress. In transcriptomic analysis, cluster analysis of differentially expressed genes revealed the relationship between tryptophan and isobutanol stress through some specific cellular functions, such as biosynthesis and transportation of amino acids, PPP, tryptophan metabolism, nicotinate/nicotinamide metabolism (e.g., nicotinamide adenine dinucleotide biosynthesis), and fatty acid metabolism.ConclusionsThe importance of tryptophan in yeast’s tolerance to isobutanol was confirmed by the recovery of isobutanol tolerance in defective strains by adding exogenous tryptophan to the growth medium. Transcriptomic analysis showed that amino acid biosynthesis- and transportation-related genes in a tryptophan biosynthesis-defective host were up-regulated under conditions similar to nitrogen starvation. This may explain why ubiquitination was required for the protein turnover. PPP metabolites may serve as precursors and cofactors in tryptophan biosynthesis to enhance isobutanol tolerance. Furthermore, the tolerance mechanism may also be linked to tryptophan downstream metabolism, including the kynurenine pathway and nicotinamide adenine dinucleotide biosynthesis. Both pathways are responsible for cellular redox balance and anti-oxidative ability. Our study highlights the central role of tryptophan in yeast’s isobutanol tolerance and offers new clues for engineering a yeast host with strong isobutanol tolerance.

Prevention of diet restriction induced hyperactivity but not body-weight reduction in rats co-treated with tryptophan: relationship with striatal serotonin and dopamine metabolism and serotonin-1A auto-receptor expression

ABSTRACT Anorexia Nervosa (AN) is an eating and behavioral disorder characterized with anxiety/depression, hyperactivity, behavioral impulsivity and psychosis. Most of the associated symptoms are related to the deficiency of serotonin (5-hydroxytryptamine: 5-HT) stores. A deficiency of 5-HT can modulate dopamine neurotransmission in the striatum to elicit hyperactivity and psychosis in AN patients. Also, the release and availability of 5-HT are modulated by serotonin-1A (5-HT1A) auto-receptor. The present study investigates the role of striatal metabolism of 5-HT and dopamine in precipitating hyperactivity in the rat model of diet restriction (DR) induced AN. The role of tryptophan (Trp) in influencing the 5-HT metabolism and the mRNA expression of 5-HT1A auto-receptor is also investigated. We find that long-term DR for 38 days reduces body-weight in rats and produces hyperactivity, similar to AN. This hyperactivity is characterized by declined striatal metabolism of both, dopamine and 5-HT. The mRNA expression of 5-HT1A auto-receptor in the raphe nuclei is also decreased. Trp co-treatment improves these deficiencies in monoamine metabolism and alleviates hyperactivity. Interestingly, DR-induced changes in body-weights are not effected by Trp co-treatment. The study suggests that the striatal metabolism of 5-HT and dopamine and mRNA expression of 5-HT1A auto-receptor has an important role in the pathogenesis of AN. The finding suggests that co-use of Trp can prevent precipitation of AN by normalizing 5-HT metabolism.

Tryptophan Metabolism via Kynurenine Pathway: Role in Solid Organ Transplantation.

Solid organ transplantation is a gold standard treatment for patients suffering from an end-stage organ disease. Patient and graft survival have vastly improved during the last couple of decades; however, the field of transplantation still encounters several unique challenges, such as a shortage of transplantable organs and increasing pool of extended criteria donor (ECD) organs, which are extremely prone to ischemia-reperfusion injury (IRI), risk of graft rejection and challenges in immune regulation. Moreover, accurate and specific biomarkers, which can timely predict allograft dysfunction and/or rejection, are lacking. The essential amino acid tryptophan and, especially, its metabolites via the kynurenine pathway has been widely studied as a contributor and a therapeutic target in various diseases, such as neuropsychiatric, autoimmune disorders, allergies, infections and malignancies. The tryptophan-kynurenine pathway has also gained interest in solid organ transplantation and a variety of experimental studies investigating its role both in IRI and immune regulation after allograft implantation was first published. In this review, the current evidence regarding the role of tryptophan and its metabolites in solid organ transplantation is presented, giving insights into molecular mechanisms and into therapeutic and diagnostic/prognostic possibilities.

Pyridoxal 5'-Phosphate-Dependent Enzymes at the Crossroads of Host-Microbe Tryptophan Metabolism.

The chemical processes taking place in humans intersects the myriad of metabolic pathways occurring in commensal microorganisms that colonize the body to generate a complex biochemical network that regulates multiple aspects of human life. The role of tryptophan (Trp) metabolism at the intersection between the host and microbes is increasingly being recognized, and multiple pathways of Trp utilization in either direction have been identified with the production of a wide range of bioactive products. It comes that a dysregulation of Trp metabolism in either the host or the microbes may unbalance the production of metabolites with potential pathological consequences. The ability to redirect the Trp flux to restore a homeostatic production of Trp metabolites may represent a valid therapeutic strategy for a variety of pathological conditions, but identifying metabolic checkpoints that could be exploited to manipulate the Trp metabolic network is still an unmet need. In this review, we put forward the hypothesis that pyridoxal 5′-phosphate (PLP)-dependent enzymes, which regulate multiple pathways of Trp metabolism in both the host and in microbes, might represent critical nodes and that modulating the levels of vitamin B6, from which PLP is derived, might represent a metabolic checkpoint to re-orienteer Trp flux for therapeutic purposes.

The Role of Tryptophan and Tyrosine in Executive Function and Reward Processing.

The serotonergic precursor tryptophan and the dopaminergic precursor tyrosine have been shown to be important modulators of mood, behaviour and cognition. Specifically, research on the function of tryptophan has characterised this molecule as particularly relevant in the context of pathological disorders such as depression. Moreover, a large body of evidence has now been accumulated to suggest that tryptophan may also be involved in executive function and reward processing. Despite some clear differentiation with tryptophan, the data reviewed in this paper illustrates that tyrosine shares similar functions with tryptophan in the regulation of executive function and reward, and that these processes in turn, rather than acting in isolation, causally influence each other.

Auxin driven indoleamine biosynthesis and the role of tryptophan as an inductive signal in Hypericum perforatum (L.).

In the 60 years since Skoog and Miller first reported the chemical redirection of plant growth the underlying biochemical mechanisms are still poorly understood, with one challenge being the capacity for applied growth regulators to act indirectly or be metabolized to active phytohormones. We hypothesized that tryptophan is metabolized to auxin, melatonin or serotonin inducing organogenesis in St. John’s wort (Hypericum perforatum L.). Root explants from two germplasm lines of St. John’s wort with altered melatonin metabolism and wildtype were incubated with auxin or tryptophan for 24, 48 or 72 h to induce regeneration. In wildtype, tryptophan had little effect on the indoleamine pathway, and was found to promote primary growth, suggesting excess tryptophan moved quickly through various secondary metabolite pathways and protein synthesis. In lines 4 and 112 tryptophan was associated with modified morphogenesis, indoleamine and auxin levels. Incubation with tryptophan increased shoot organogenesis while incubation with auxin led to root regeneration. The established paradigm of thought views tryptophan primarily as a precursor for auxin and indoleamines, among other metabolites, and mediation of auxin action by the indoleamines as a one-way interaction. We propose that these processes run in both directions with auxin modifying indoleamine biosynthesis and the melatonin:serotonin balance contributing to its effects on plant morphogenesis, and that tryptophan also functions as an inductive signal to mediate diverse phytochemical and morphogenetic pathways.