International Journal of Molecular Sciences

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3 pages, 414 KiB

Open AccessEditorial

Tryptophan in Nutrition and Health

by Burkhard Poeggeler, Sandeep Kumar Singh and Miguel A. Pappolla

Int. J. Mol. Sci. 2022, 23(10), 5455; https://doi.org/10.3390/ijms23105455 - 13 May 2022

Cited by 7 | Viewed by 3806

Abstract

Tryptophan is a rate-limiting essential amino acid and a unique building block of peptides and proteins [...] Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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Research

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13 pages, 1893 KiB

Open AccessArticle

Molecular Basis of Interactions between the Antibiotic Nitrofurantoin and Human Serum Albumin: A Mechanism for the Rapid Drug Blood Transportation

by Antonella Calderaro, Alessandro Maugeri, Salvatore Magazù, Giuseppina Laganà, Michele Navarra and Davide Barreca

Int. J. Mol. Sci. 2021, 22(16), 8740; https://doi.org/10.3390/ijms22168740 - 14 Aug 2021

Cited by 11 | Viewed by 3560

Abstract

Nitrofurantoin is an antimicrobial agent obtained through the addition of a nitro group and a side chain containing hydantoin to a furan ring. The interactions of the antibiotic with human serum albumin (HSA) have been investigated by fluorescence, UV-VIS, Fourier transform infrared spectroscopy [...] Read more.

Nitrofurantoin is an antimicrobial agent obtained through the addition of a nitro group and a side chain containing hydantoin to a furan ring. The interactions of the antibiotic with human serum albumin (HSA) have been investigated by fluorescence, UV-VIS, Fourier transform infrared spectroscopy (FTIR) spectroscopy, and protein-ligand docking studies. The fluorescence studies indicate that the binding site of the additive involves modifications of the environment around Trp214 at the level of subdomain IIA. Fluorescence and UV-VIS spectroscopy, displacement studies, and FTIR experiments show the association mode of nitrofurantoin to HSA, suggesting that the primary binding site of the antibiotic is located in Sudlow’s site I. Molecular modeling suggests that nitrofurantoin is involved in the formation of hydrogen bonds with Trp214, Arg218, and Ser454, and is located in the hydrophobic cavity of subdomain IIA. Moreover, the curve-fitting results of the infrared Amide I’ band indicate that the binding of nitrofurantoin induces little change in the protein secondary structure. Overall, these data clarify the blood transportation process of nitrofurantoin and its rapid transfer to the kidney for its elimination, hence leading to a better understanding of its biological effects and being able to design other molecules, based on nitrofurantoin, with a higher biological potential. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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14 pages, 3959 KiB

Open AccessArticle

Degradation Products of Tryptophan in Cell Culture Media: Contribution to Color and Toxicity

by Alisa Schnellbaecher, Anton Lindig, Maxime Le Mignon, Tim Hofmann, Brit Pardon, Stephanie Bellmaine and Aline Zimmer

Int. J. Mol. Sci. 2021, 22(12), 6221; https://doi.org/10.3390/ijms22126221 - 9 Jun 2021

Cited by 6 | Viewed by 3579

Abstract

Biomanufacturing processes may be optimized by storing cell culture media at room temperature, but this is currently limited by their instability and change in color upon long-term storage. This study demonstrates that one of the critical contributing factors toward media browning is tryptophan. [...] Read more.

Biomanufacturing processes may be optimized by storing cell culture media at room temperature, but this is currently limited by their instability and change in color upon long-term storage. This study demonstrates that one of the critical contributing factors toward media browning is tryptophan. LC-MS technology was utilized to identify tryptophan degradation products, which are likely formed primarily from oxidation reactions. Several of the identified compounds were shown to contribute significantly to color in solutions but also to exhibit toxicity against CHO cells. A cell-culture-compatible antioxidant, a-ketoglutaric acid, was found to be an efficient cell culture media additive for stabilizing components against degradation, inhibiting the browning of media formulations, and decreasing ammonia production, thus providing a viable method for developing room-temperature stable cell culture media. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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17 pages, 3039 KiB

Open AccessArticle

Effects of Tyrosine and Tryptophan Supplements on the Vital Indicators in Mice Differently Prone to Diet-Induced Obesity

by Ivan V. Gmoshinski, Vladimir A. Shipelin, Nikita V. Trusov, Sergey A. Apryatin, Kristina V. Mzhelskaya, Antonina A. Shumakova, Andrey N. Timonin, Nikolay A. Riger and Dmitry B. Nikityuk

Int. J. Mol. Sci. 2021, 22(11), 5956; https://doi.org/10.3390/ijms22115956 - 31 May 2021

Cited by 6 | Viewed by 6611

Abstract

We studied the effects of the addition of large neutral amino acids, such as tyrosine (Tyr) and tryptophan (Trp), in mice DBA/2J and tetrahybrid mice DBCB receiving a high-fat, high-carbohydrate diet (HFCD) for 65 days. The locomotor activity, anxiety, muscle tone, mass of [...] Read more.

We studied the effects of the addition of large neutral amino acids, such as tyrosine (Tyr) and tryptophan (Trp), in mice DBA/2J and tetrahybrid mice DBCB receiving a high-fat, high-carbohydrate diet (HFCD) for 65 days. The locomotor activity, anxiety, muscle tone, mass of internal organs, liver morphology, adipokines, cytokines, and biochemical indices of animals were assessed. The Tyr supplementation potentiated increased anxiety in EPM and contributed to a muscle tone increase, a decrease in the AST/ALT ratio, and an increase in protein anabolism in both mice strains. Tyr contributed to a decrease in liver fatty degeneration and ALT reduction only in DBCB that were sensitive to the development of obesity. The addition of Trp caused an increase in muscle tone and potentiated an increase in anxiety with age in animals of both genotypes. Trp had toxic effects on the livers of mice, which was manifested in increased fatty degeneration in DBCB, edema, and the appearance of micronuclei in DBA/2J. The main identified effects of Tyr on mice are considered in the light of its modulating effect on the dopamine neurotransmitter metabolism, while for the Trp supplement, effects were presumably associated with the synthesis of its toxic metabolites by representatives of the intestinal microflora. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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12 pages, 2712 KiB

Open AccessArticle

A Tryptophan-Deficient Diet Induces Gut Microbiota Dysbiosis and Increases Systemic Inflammation in Aged Mice

by Ibrahim Yusufu, Kehong Ding, Kathryn Smith, Umesh D. Wankhade, Bikash Sahay, G. Taylor Patterson, Rafal Pacholczyk, Satish Adusumilli, Mark W. Hamrick, William D. Hill, Carlos M. Isales and Sadanand Fulzele

Int. J. Mol. Sci. 2021, 22(9), 5005; https://doi.org/10.3390/ijms22095005 - 8 May 2021

Cited by 49 | Viewed by 17281

Abstract

The gut microflora is a vital component of the gastrointestinal (GI) system that regulates local and systemic immunity, inflammatory response, the digestive system, and overall health. Older people commonly suffer from inadequate nutrition or poor diets, which could potentially alter the gut microbiota. [...] Read more.

The gut microflora is a vital component of the gastrointestinal (GI) system that regulates local and systemic immunity, inflammatory response, the digestive system, and overall health. Older people commonly suffer from inadequate nutrition or poor diets, which could potentially alter the gut microbiota. The essential amino acid (AA) tryptophan (TRP) is a vital diet component that plays a critical role in physiological stress responses, neuropsychiatric health, oxidative systems, inflammatory responses, and GI health. The present study investigates the relationship between varied TRP diets, the gut microbiome, and inflammatory responses in an aged mouse model. We fed aged mice either a TRP-deficient (0.1%), TRP-recommended (0.2%), or high-TRP (1.25%) diet for eight weeks and observed changes in the gut bacterial environment and the inflammatory responses via cytokine analysis (IL-1a, IL-6, IL-17A, and IL-27). The mice on the TRP-deficient diets showed changes in their bacterial abundance of Coriobacteriia class, Acetatifactor genus, Lachnospiraceae family, Enterococcus faecalis species, Clostridium sp genus, and Oscillibacter genus. Further, these mice showed significant increases in IL-6, IL-17A, and IL-1a and decreased IL-27 levels. These data suggest a direct association between dietary TRP content, the gut microbiota microenvironment, and inflammatory responses in aged mice models. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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13 pages, 1101 KiB

Open AccessArticle

Supplementing with L-Tryptophan Increases Medium Protein and Alters Expression of Genes and Proteins Involved in Milk Protein Synthesis and Energy Metabolism in Bovine Mammary Cells

by Jay Ronel V. Conejos, Jalil Ghassemi Nejad, Jung-Eun Kim, Jun-Ok Moon, Jae-Sung Lee and Hong-Gu Lee

Int. J. Mol. Sci. 2021, 22(5), 2751; https://doi.org/10.3390/ijms22052751 - 9 Mar 2021

Cited by 11 | Viewed by 3766

Abstract

The objective of this study was to investigate the effects of supplementing with L-tryptophan (L-Trp) on milk protein synthesis using an immortalized bovine mammary epithelial (MAC-T) cell line. Cells were treated with 0, 0.3, 0.6, 0.9, 1.2, and 1.5 mM of supplemental L-Trp, [...] Read more.

The objective of this study was to investigate the effects of supplementing with L-tryptophan (L-Trp) on milk protein synthesis using an immortalized bovine mammary epithelial (MAC-T) cell line. Cells were treated with 0, 0.3, 0.6, 0.9, 1.2, and 1.5 mM of supplemental L-Trp, and the most efficient time for protein synthesis was determined by measuring cell, medium, and total protein at 0, 24, 48, 72, and 96 h. Time and dose tests showed that the 48 h incubation time and a 0.9 mM dose of L-Trp were the optimal values. The mechanism of milk protein synthesis was elucidated through proteomic analysis to identify the metabolic pathway involved. When L-Trp was supplemented, extracellular protein (medium protein) reached its peak at 48 h, whereas intracellular cell protein reached its peak at 96 h with all L-Trp doses. β-casein mRNA gene expression and genes related to milk protein synthesis, such as mammalian target of rapamycin (mTOR) and ribosomal protein 6 (RPS6) genes, were also stimulated (p < 0.05). Overall, there were 51 upregulated and 59 downregulated proteins, many of which are involved in protein synthesis. The results of protein pathway analysis showed that L-Trp stimulated glycolysis, the pentose phosphate pathway, and ATP synthesis, which are pathways involved in energy metabolism. Together, these results demonstrate that L-Trp supplementation, particularly at 0.9 mM, is an effective stimulus in β-casein synthesis by stimulating genes, proteins, and pathways related to protein and energy metabolism. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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11 pages, 3009 KiB

Open AccessArticle

Strong Dependence between Tryptophan-Related Fluorescence of Urine and Malignant Melanoma

by Anna Birková, Marcela Valko-Rokytovská, Beáta Hubková, Marianna Zábavníková and Mária Mareková

Int. J. Mol. Sci. 2021, 22(4), 1884; https://doi.org/10.3390/ijms22041884 - 13 Feb 2021

Cited by 9 | Viewed by 2264

Abstract

Urine autofluorescence at 295 nm is significantly higher in patients with malignant melanoma at each clinical stage compared to the healthy group. The largest difference is in the early-stages and without metastases. With increasing stage, the autofluorescence at 295 nm decreases. There is [...] Read more.

Urine autofluorescence at 295 nm is significantly higher in patients with malignant melanoma at each clinical stage compared to the healthy group. The largest difference is in the early-stages and without metastases. With increasing stage, the autofluorescence at 295 nm decreases. There is also a significant negative correlation between autofluorescence and Clark classification. Based on our results, it is assumed that the way malignant melanoma grows also affects urinary autofluorescence. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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19 pages, 3350 KiB

Open AccessArticle

Tryptophan Derivatives by Saccharomyces cerevisiae EC1118: Evaluation, Optimization, and Production in a Soybean-Based Medium

by Michele Dei Cas, Ileana Vigentini, Sara Vitalini, Antonella Laganaro, Marcello Iriti, Rita Paroni and Roberto Foschino

Int. J. Mol. Sci. 2021, 22(1), 472; https://doi.org/10.3390/ijms22010472 - 5 Jan 2021

Cited by 10 | Viewed by 8009

Abstract

Given the pharmacological properti es and the potential role of kynurenic acid (KYNA) in human physiology and the pleiotropic activity of the neurohormone melatonin (MEL) involved in physiological and immunological functions and as regulator of antioxidant enzymes, this study aimed at evaluating the [...] Read more.

Given the pharmacological properti es and the potential role of kynurenic acid (KYNA) in human physiology and the pleiotropic activity of the neurohormone melatonin (MEL) involved in physiological and immunological functions and as regulator of antioxidant enzymes, this study aimed at evaluating the capability of Saccharomyces cerevisiae EC1118 to release tryptophan derivatives (dTRPs) from the kynurenine (KYN) and melatonin pathways. The setting up of the spectroscopic and chromatographic conditions for the quantification of the dTRPs in LC-MS/MS system, the optimization of dTRPs’ production in fermentative and whole-cell biotransformation approaches and the production of dTRPs in a soybean-based cultural medium naturally enriched in tryptophan, as a case of study, were included in the experimental plan. Variable amounts of dTRPs, with a prevalence of metabolites of the KYN pathway, were detected. The LC-MS/MS analysis showed that the compound synthesized at highest concentration is KYNA that reached 9.146 ± 0.585 mg/L in fermentation trials in a chemically defined medium at 400 mg/L TRP. Further experiments in a soybean-based medium confirm KYNA as the main dTRPs, whereas the other dTRPs reached very lower concentrations. While detectable quantities of melatonin were never observed, two MEL isomers were successfully measured in laboratory media. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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19 pages, 2758 KiB

Open AccessArticle

The Effect of Chronic Mild Stress and Escitalopram on the Expression and Methylation Levels of Genes Involved in the Oxidative and Nitrosative Stresses as Well as Tryptophan Catabolites Pathway in the Blood and Brain Structures

by Paulina Wigner, Ewelina Synowiec, Paweł Jóźwiak, Piotr Czarny, Michał Bijak, Katarzyna Białek, Janusz Szemraj, Piotr Gruca, Mariusz Papp and Tomasz Śliwiński

Int. J. Mol. Sci. 2021, 22(1), 10; https://doi.org/10.3390/ijms22010010 - 22 Dec 2020

Cited by 10 | Viewed by 3261

Abstract

Previous studies suggest that depression may be associated with reactive oxygen species overproduction and disorders of the tryptophan catabolites pathway. Moreover, one-third of patients do not respond to conventional pharmacotherapy. Therefore, the study investigates the molecular effect of escitalopram on the expression of [...] Read more.

Previous studies suggest that depression may be associated with reactive oxygen species overproduction and disorders of the tryptophan catabolites pathway. Moreover, one-third of patients do not respond to conventional pharmacotherapy. Therefore, the study investigates the molecular effect of escitalopram on the expression of Cat, Gpx1/4, Nos1/2, Tph1/2, Ido1, Kmo, and Kynu and promoter methylation in the hippocampus, amygdala, cerebral cortex, and blood of rats exposed to CMS (chronic mild stress). The animals were exposed to CMS for two or seven weeks followed by escitalopram treatment for five weeks. The mRNA and protein expression of the genes were analysed using the TaqMan Gene Expression Assay and Western blotting, while the methylation was determined using methylation-sensitive high-resolution melting. The CMS caused an increase of Gpx1 and Nos1 mRNA expression in the hippocampus, which was normalised by escitalopram administration. Moreover, Tph1 and Tph2 mRNA expression in the cerebral cortex was increased in stressed rats after escitalopram therapy. The methylation status of the Cat promoter was decreased in the hippocampus and cerebral cortex of the rats after escitalopram therapy. The Gpx4 protein levels were decreased following escitalopram compared to the stressed/saline group. It appears that CMS and escitalopram influence the expression and methylation of the studied genes. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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19 pages, 2585 KiB

Open AccessArticle

Effect of Tryptophan-Derived AhR Ligands, Kynurenine, Kynurenic Acid and FICZ, on Proliferation, Cell Cycle Regulation and Cell Death of Melanoma Cells—In Vitro Studies

by Katarzyna Walczak, Ewa Langner, Anna Makuch-Kocka, Monika Szelest, Karolina Szalast, Sebastian Marciniak and Tomasz Plech

Int. J. Mol. Sci. 2020, 21(21), 7946; https://doi.org/10.3390/ijms21217946 - 26 Oct 2020

Cited by 33 | Viewed by 3914

Abstract

Tryptophan metabolites: kynurenine (KYN), kynurenic acid (KYNA) and 6-formylindolo[3,2-b]carbazole (FICZ) are considered aryl hydrocarbon receptor (AhR) ligands. AhR is mainly expressed in barrier tissues, including skin, and is involved in various physiological and pathological processes in skin. We studied the effect of KYN, [...] Read more.

Tryptophan metabolites: kynurenine (KYN), kynurenic acid (KYNA) and 6-formylindolo[3,2-b]carbazole (FICZ) are considered aryl hydrocarbon receptor (AhR) ligands. AhR is mainly expressed in barrier tissues, including skin, and is involved in various physiological and pathological processes in skin. We studied the effect of KYN, KYNA and FICZ on melanocyte and melanoma A375 and RPMI7951 cell toxicity, proliferation and cell death. KYN and FICZ inhibited DNA synthesis in both melanoma cell lines, but RPMI7951 cells were more resistant to pharmacological treatment. Tested compounds were toxic to melanoma cells but not to normal human adult melanocytes. Changes in the protein level of cyclin D1, CDK4 and retinoblastoma tumor suppressor protein (Rb) phosphorylation revealed different mechanisms of action of individual AhR ligands. Importantly, all tryptophan metabolites induced necrosis, but only KYNA and FICZ promoted apoptosis in melanoma A375 cells. This effect was not observed in RPMI7951 cells. KYN, KYNA and FICZ in higher concentrations inhibited the protein level of AhR but did not affect the gene expression. To conclude, despite belonging to the group of AhR ligands, KYN, KYNA and FICZ exerted different effects on proliferation, toxicity and induction of cell death in melanoma cells in vitro. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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Review

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16 pages, 1394 KiB

Open AccessReview

The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine

by Ning Liu, Shiqiang Sun, Pengjie Wang, Yanan Sun, Qingjuan Hu and Xiaoyu Wang

Int. J. Mol. Sci. 2021, 22(15), 7931; https://doi.org/10.3390/ijms22157931 - 25 Jul 2021

Cited by 86 | Viewed by 13379

Abstract

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and [...] Read more.

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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32 pages, 1069 KiB

Open AccessReview

Tryptophan Metabolism via Kynurenine Pathway: Role in Solid Organ Transplantation

by Ruta Zulpaite, Povilas Miknevicius, Bettina Leber, Kestutis Strupas, Philipp Stiegler and Peter Schemmer

Int. J. Mol. Sci. 2021, 22(4), 1921; https://doi.org/10.3390/ijms22041921 - 15 Feb 2021

Cited by 14 | Viewed by 3280

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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16 pages, 555 KiB

Open AccessReview

Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology

by George Anderson, Annalucia Carbone and Gianluigi Mazzoccoli

Int. J. Mol. Sci. 2021, 22(4), 1597; https://doi.org/10.3390/ijms22041597 - 5 Feb 2021

Cited by 37 | Viewed by 6232

Abstract

The metabolism of tryptophan is intimately associated with the differential regulation of diverse physiological processes, including in the regulation of responses to severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection that underpins the COVID-19 pandemic. Two important products of tryptophan metabolism, viz kynurenine and [...] Read more.

The metabolism of tryptophan is intimately associated with the differential regulation of diverse physiological processes, including in the regulation of responses to severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection that underpins the COVID-19 pandemic. Two important products of tryptophan metabolism, viz kynurenine and interleukin (IL)4-inducible1 (IL41)-driven indole 3 pyruvate (I3P), activate the aryl hydrocarbon receptor (AhR), thereby altering the nature of immune responses to SARS-CoV-2 infection. AhR activation dysregulates the initial pro-inflammatory cytokines production driven by neutrophils, macrophages, and mast cells, whilst AhR activation suppresses the endogenous antiviral responses of natural killer cells and CD8+ T cells. Such immune responses become further dysregulated by the increased and prolonged pro-inflammatory cytokine suppression of pineal melatonin production coupled to increased gut dysbiosis and gut permeability. The suppression of pineal melatonin and gut microbiome-derived butyrate, coupled to an increase in circulating lipopolysaccharide (LPS) further dysregulates the immune response. The AhR mediates its effects via alterations in the regulation of mitochondrial function in immune cells. The increased risk of severe/fatal SARS-CoV-2 infection by high risk conditions, such as elderly age, obesity, and diabetes are mediated by these conditions having expression levels of melatonin, AhR, butyrate, and LPS that are closer to those driven by SARS-CoV-2 infection. This has a number of future research and treatment implications, including the utilization of melatonin and nutraceuticals that inhibit the AhR, including the polyphenols, epigallocatechin gallate (EGCG), and resveratrol. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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31 pages, 1742 KiB

Open AccessReview

A New Insight into the Potential Role of Tryptophan-Derived AhR Ligands in Skin Physiological and Pathological Processes

by Monika Szelest, Katarzyna Walczak and Tomasz Plech

Int. J. Mol. Sci. 2021, 22(3), 1104; https://doi.org/10.3390/ijms22031104 - 22 Jan 2021

Cited by 50 | Viewed by 7231

Abstract

The aryl hydrocarbon receptor (AhR) plays a crucial role in environmental responses and xenobiotic metabolism, as it controls the transcription profiles of several genes in a ligand-specific and cell-type-specific manner. Various barrier tissues, including skin, display the expression of AhR. Recent studies revealed [...] Read more.

The aryl hydrocarbon receptor (AhR) plays a crucial role in environmental responses and xenobiotic metabolism, as it controls the transcription profiles of several genes in a ligand-specific and cell-type-specific manner. Various barrier tissues, including skin, display the expression of AhR. Recent studies revealed multiple roles of AhR in skin physiology and disease, including melanogenesis, inflammation and cancer. Tryptophan metabolites are distinguished among the groups of natural and synthetic AhR ligands, and these include kynurenine, kynurenic acid and 6-formylindolo[3,2-b]carbazole (FICZ). Tryptophan derivatives can affect and regulate a variety of signaling pathways. Thus, the interest in how these substances influence physiological and pathological processes in the skin is expanding rapidly. The widespread presence of these substances and potential continuous exposure of the skin to their biological effects indicate the important role of AhR and its ligands in the prevention, pathogenesis and progression of skin diseases. In this review, we summarize the current knowledge of AhR in skin physiology. Moreover, we discuss the role of AhR in skin pathological processes, including inflammatory skin diseases, pigmentation disorders and cancer. Finally, the impact of FICZ, kynurenic acid, and kynurenine on physiological and pathological processes in the skin is considered. However, the mechanisms of how AhR regulates skin function require further investigation. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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25 pages, 24501 KiB

Open AccessReview

5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology

by Massimo E. Maffei

Int. J. Mol. Sci. 2021, 22(1), 181; https://doi.org/10.3390/ijms22010181 - 26 Dec 2020

Cited by 97 | Viewed by 39047

Abstract

L-5-hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed [...] Read more.

L-5-hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed to melatonin (N-acetyl-5-methoxytryptamine). 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis. In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials. The physiological role of 5-HTP in the treatment of depression, anxiety, panic, sleep disorders, obesity, myoclonus and serotonin syndrome are also discussed. 5-HTP toxicity and the occurrence of toxic impurities present in tryptophan and 5-HTP preparations are also discussed. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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22 pages, 4147 KiB

Open AccessReview

The Uniqueness of Tryptophan in Biology: Properties, Metabolism, Interactions and Localization in Proteins

by Sailen Barik

Int. J. Mol. Sci. 2020, 21(22), 8776; https://doi.org/10.3390/ijms21228776 - 20 Nov 2020

Cited by 107 | Viewed by 14315

Abstract

Tryptophan (Trp) holds a unique place in biology for a multitude of reasons. It is the largest of all twenty amino acids in the translational toolbox. Its side chain is indole, which is aromatic with a binuclear ring structure, whereas those of Phe, [...] Read more.

Tryptophan (Trp) holds a unique place in biology for a multitude of reasons. It is the largest of all twenty amino acids in the translational toolbox. Its side chain is indole, which is aromatic with a binuclear ring structure, whereas those of Phe, Tyr, and His are single-ring aromatics. In part due to these elaborate structural features, the biosynthetic pathway of Trp is the most complex and the most energy-consuming among all amino acids. Essential in the animal diet, Trp is also the least abundant amino acid in the cell, and one of the rarest in the proteome. In most eukaryotes, Trp is the only amino acid besides Met, which is coded for by a single codon, namely UGG. Due to the large and hydrophobic π-electron surface area, its aromatic side chain interacts with multiple other side chains in the protein, befitting its strategic locations in the protein structure. Finally, several Trp derivatives, namely tryptophylquinone, oxitriptan, serotonin, melatonin, and tryptophol, have specialized functions. Overall, Trp is a scarce and precious amino acid in the cell, such that nature uses it parsimoniously, for multiple but selective functions. Here, the various aspects of the uniqueness of Trp are presented in molecular terms. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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21 pages, 1893 KiB

Open AccessReview

Developmental Programming and Reprogramming of Hypertension and Kidney Disease: Impact of Tryptophan Metabolism

by Chien-Ning Hsu and You-Lin Tain

Int. J. Mol. Sci. 2020, 21(22), 8705; https://doi.org/10.3390/ijms21228705 - 18 Nov 2020

Cited by 51 | Viewed by 8200

Abstract

The concept that hypertension and chronic kidney disease (CKD) originate in early life has emerged recently. During pregnancy, tryptophan is crucial for maternal protein synthesis and fetal development. On one hand, impaired tryptophan metabolic pathway in pregnancy impacts fetal programming, resulting in the [...] Read more.

The concept that hypertension and chronic kidney disease (CKD) originate in early life has emerged recently. During pregnancy, tryptophan is crucial for maternal protein synthesis and fetal development. On one hand, impaired tryptophan metabolic pathway in pregnancy impacts fetal programming, resulting in the developmental programming of hypertension and kidney disease in adult offspring. On the other hand, tryptophan-related interventions might serve as reprogramming strategies to prevent a disease from occurring. In the present review, we aim to summarize (1) the three major tryptophan metabolic pathways, (2) the impact of tryptophan metabolism in pregnancy, (3) the interplay occurring between tryptophan metabolites and gut microbiota on the production of uremic toxins, (4) the role of tryptophan-derived metabolites-induced hypertension and CKD of developmental origin, (5) the therapeutic options in pregnancy that could aid in reprogramming adverse effects to protect offspring against hypertension and CKD, and (6) possible mechanisms linking tryptophan metabolism to developmental programming of hypertension and kidney disease. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health)

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