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Tryptophan in Nutrition and Health 3.0
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Tryptophan in Nutrition and Health 3.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 13098

Special Issue Editor

Dr. Burkhard Poeggeler

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Guest Editor
Department of Physiology, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, Faculty of Biology Georg August University Göttingen, Göttingen and Goettingen Research Campus, Göttingen, Am Türmchen 3, D-33332 Gütersloh, Germany
Interests: aging; amino acids; antioxidants; inflammaging; melatonin; product development; tryptophan
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tryptophan is a rate-limiting essential amino acid and thus a building block of life. Tryptophan administration can increase brain serotonin synthesis and release. This, in turn, can improve mood and sleep. Tryptophan is also the precursor of melatonin, neuroactive kynurenines, and niacin. Current research on the physiology and pathophysiology of tryptophan metabolism has revealed the central role of tryptophan and its metabolites as master molecular regulators of neurotransmission and neuromodulation. The ratio of tryptophan to kynurenine is a key parameter determining and reflecting endogenous inflammation and regeneration. Tryptophan metabolites such as melatonin and structurally related microbial agents act as potent antioxidant and bioenergetic agents. This Special Issue will examine the key tryptophan pathways and their molecular targets. The latest developments in tryptophan research are the focus of this article collection, and the studies herein will demonstrate the relevance of tryptophan and its metabolites in nutrition and health. The discovery of a broad range of bioactive compounds derived from tryptophan will enable a better understanding of the unique role of this amino acid in disease prevention and treatment.

Dr. Burkhard Poeggeler
Guest Editor

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Keywords

  • antioxidants
  • kynurenine
  • melatonin
  • serotonin
  • tryptophan

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Related Special Issues

Published Papers (7 papers)

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Research

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13 pages, 22639 KiB  
Article
Biosynthetic Pathways of Tryptophan Metabolites in Saccharomyces cerevisiae Strain: Insights and Implications
by Hsin-Chieh Kung, Ngoc-Han Bui, Bo-Wun Huang, Nicholas Kiprotich Cheruiyot and Guo-Ping Chang-Chien
Int. J. Mol. Sci. 2024, 25(9), 4747; https://doi.org/10.3390/ijms25094747 - 26 Apr 2024
Viewed by 1086
Abstract
Tryptophan metabolites, such as 5-hydroxytryptophan (5-HTP), serotonin, and melatonin, hold significant promise as supplements for managing various mood-related disorders, including depression and insomnia. However, their chemical production via chemical synthesis and phytochemical extraction presents drawbacks, such as the generation of toxic byproducts and [...] Read more.
Tryptophan metabolites, such as 5-hydroxytryptophan (5-HTP), serotonin, and melatonin, hold significant promise as supplements for managing various mood-related disorders, including depression and insomnia. However, their chemical production via chemical synthesis and phytochemical extraction presents drawbacks, such as the generation of toxic byproducts and low yields. In this study, we explore an alternative approach utilizing S. cerevisiae STG S101 for biosynthesis. Through a series of eleven experiments employing different combinations of tryptophan supplementation, Tween 20, and HEPES buffer, we investigated the production of these indolamines. The tryptophan metabolites were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Notably, setups replacing peptone in the YPD media with tryptophan (Run 3) and incorporating tryptophan along with 25 mM HEPES buffer (Run 4) demonstrated successful biosynthesis of 5-HTP and serotonin. The highest 5-HTP and serotonin concentrations were 58.9 ± 16.0 mg L−1 and 0.0650 ± 0.00211 mg L−1, respectively. Melatonin concentrations were undetected in all the setups. These findings underscore the potential of using probiotic yeast strains as a safer and conceivably more cost-effective alternative for indolamine synthesis. The utilization of probiotic strains presents a promising avenue, potentially offering scalability, sustainability, reduced environmental impact, and feasibility for large-scale production. Full article
(This article belongs to the Special Issue Tryptophan in Nutrition and Health 3.0)
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20 pages, 677 KiB  
Article
Effects of Rumen-Protected L-Tryptophan Supplementation on Productivity, Physiological Indicators, Blood Profiles, and Heat Shock Protein Gene Expression in Lactating Holstein Cows under Heat Stress Conditions
by Jang-Hoon Jo, Ghassemi Nejad Jalil, Won-Seob Kim, Jun-Ok Moon, Sung-Dae Lee, Chan-Ho Kwon and Hong-Gu Lee
Int. J. Mol. Sci. 2024, 25(2), 1217; https://doi.org/10.3390/ijms25021217 - 19 Jan 2024
Cited by 2 | Viewed by 1701
Abstract
In this study, we examined the effects of rumen-protected L-tryptophan supplementation on the productivity and physiological metabolic indicators in lactating Holstein cows under heat stress conditions. The study involved eight early lactating Holstein cows (days in milk = 40 ± 9 days; milk [...] Read more.
In this study, we examined the effects of rumen-protected L-tryptophan supplementation on the productivity and physiological metabolic indicators in lactating Holstein cows under heat stress conditions. The study involved eight early lactating Holstein cows (days in milk = 40 ± 9 days; milk yield 30 ± 1.5 kg/day; parity 1.09 ± 0.05, p < 0.05), four cows per experiment, with environmentally controlled chambers. In each experiment, two distinct heat stress conditions were created: a low-temperature and low-humidity (LTLH) condition at 25 °C with 35–50% humidity and a high-temperature and high-humidity (HTHH) condition at 31 °C with 80–95% humidity. During the adaptation phase, the cows were subjected to LTLH and HTHH conditions for 3 days. This was followed by a 4-day heat stress phase and then by a 7-day phase of heat stress, which were complemented by supplementation with rumen-protected L-tryptophan (ACT). The findings revealed that supplementation with ACT increased dry matter intake as well as milk yield and protein and decreased water intake, heart rate, and rectal temperature in the HTHH group (p < 0.05). For plateletcrit (PCT, p = 0.0600), the eosinophil percentage (EOS, p = 0.0880) showed a tendency to be lower, while the monocyte (MONO) and large unstained cells (LUC) amounts were increased in both groups (p < 0.05). Albumin and glucose levels were lower in the HTHH group (p < 0.05). The gene expressions of heat shock proteins 70 and 90 in the peripheral blood mononuclear cells were higher in the ACT group (HTHH, p < 0.05). These results suggest that ACT supplementation improved productivity, physiological indicators, blood characteristics, and gene expression in the peripheral blood mononuclear cells of early lactating Holstein cows under heat-stress conditions. In particular, ACT supplementation objectively relieved stress in these animals, suggesting that L-tryptophan has potential as a viable solution for combating heat-stress-induced effects on the cattle in dairy farming. Full article
(This article belongs to the Special Issue Tryptophan in Nutrition and Health 3.0)
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11 pages, 1148 KiB  
Article
Tryptophan Metabolism in Postmenopausal Women with Functional Constipation
by Aleksandra Blonska, Marcin Chojnacki, Anna Macieja, Janusz Blasiak, Ireneusz Majsterek, Jan Chojnacki and Tomasz Poplawski
Int. J. Mol. Sci. 2024, 25(1), 273; https://doi.org/10.3390/ijms25010273 - 24 Dec 2023
Cited by 2 | Viewed by 1439
Abstract
Constipation belongs to conditions commonly reported by postmenopausal women, but the mechanism behind this association is not fully known. The aim of the present study was to determine the relationship between some metabolites of tryptophan (TRP) and the occurrence and severity of abdominal [...] Read more.
Constipation belongs to conditions commonly reported by postmenopausal women, but the mechanism behind this association is not fully known. The aim of the present study was to determine the relationship between some metabolites of tryptophan (TRP) and the occurrence and severity of abdominal symptoms (Rome IV) in postmenopausal women with functional constipation (FC, n = 40) as compared with age-adjusted postmenopausal women without FC. All women controlled their TRP intake in their daily diet. Urinary levels of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and 3-indoxyl sulfate (indican, 3-IS), were determined by liquid chromatography/tandem mass spectrometry. Dysbiosis was assessed by a hydrogen–methane breath test. Women with FC consumed less TRP and had a lower urinary level of 5-HIAA, but higher levels of KYN and 3-IS compared with controls. The severity of symptoms showed a negative correlation with the 5-HIAA level, and a positive correlation with the 3-IS level. In conclusion, changes in TRP metabolism may contribute to FC in postmenopausal women, and dysbiosis may underlie this contribution. Full article
(This article belongs to the Special Issue Tryptophan in Nutrition and Health 3.0)
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13 pages, 4020 KiB  
Article
Tryptophan-Starved Human Cells Overexpressing Tryptophanyl-tRNA Synthetase Enhance High-Affinity Tryptophan Uptake via Enzymatic Production of Tryptophanyl-AMP
by Takumi Yokosawa and Keisuke Wakasugi
Int. J. Mol. Sci. 2023, 24(20), 15453; https://doi.org/10.3390/ijms242015453 - 22 Oct 2023
Cited by 3 | Viewed by 1349
Abstract
Our previous study demonstrated that L-tryptophan (Trp)-depleted cells display a marked enhancement in Trp uptake facilitated by extracellular tryptophanyl-tRNA synthetase (TrpRS). Here, we show that Trp uptake into TrpRS-overexpressing cells is also markedly elevated upon Trp starvation. These findings indicate that a Trp-deficient [...] Read more.
Our previous study demonstrated that L-tryptophan (Trp)-depleted cells display a marked enhancement in Trp uptake facilitated by extracellular tryptophanyl-tRNA synthetase (TrpRS). Here, we show that Trp uptake into TrpRS-overexpressing cells is also markedly elevated upon Trp starvation. These findings indicate that a Trp-deficient condition is critical for Trp uptake, not only into cells to which TrpRS protein has been added but also into TrpRS-overexpressing cells. We also show that overexpression of TrpRS mutants, which cannot synthesize tryptophanyl-AMP, does not promote Trp uptake, and that inhibition of tryptophanyl-AMP synthesis suppresses this uptake. Overall, these data suggest that tryptophanyl-AMP production by TrpRS is critical for high-affinity Trp uptake. Full article
(This article belongs to the Special Issue Tryptophan in Nutrition and Health 3.0)
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19 pages, 895 KiB  
Article
Tryptophan Modulatory Role in European Seabass (Dicentrarchus labrax) Immune Response to Acute Inflammation under Stressful Conditions
by Marina Machado, Diogo Peixoto, Paulo Santos, Ana Ricardo, Inês Duarte, Inês Carvalho, Cláudia Aragão, Rita Azeredo and Benjamín Costas
Int. J. Mol. Sci. 2022, 23(20), 12475; https://doi.org/10.3390/ijms232012475 - 18 Oct 2022
Cited by 5 | Viewed by 2047
Abstract
The present work aimed to study the role of dietary tryptophan supplementation in modulating the European seabass (Dicentrarchus labrax) immune condition during stressful rearing conditions (i.e., 15 days exposure to high density), as well as the immune response to acute inflammation [...] Read more.
The present work aimed to study the role of dietary tryptophan supplementation in modulating the European seabass (Dicentrarchus labrax) immune condition during stressful rearing conditions (i.e., 15 days exposure to high density), as well as the immune response to acute inflammation after intraperitoneal injection of a bacterial pathogen. Stress alone did not compromise seabass health indicators. In contrast, a clear peripheral and local inflammatory response was observed in response to the inoculated bacteria. Moreover, exposure to a high stocking density seemed to exacerbate the inflammatory response at early sampling points, compared to fish stocked at a lower density. In contrast, stressed fish presented some immune-suppressing effects on the T-cell surface glycoprotein receptor expressions at a late sampling point following inflammation. Regarding the effects of dietary tryptophan, no changes were observed on seabass immune indicators prior to inflammation, while a small number of immunosuppressive effects were observed in response to inflammation, supporting tryptophan’s role in the promotion of immune-tolerance signals during inflammation. Nonetheless, tryptophan dietary supplementation improved the inflammatory response against a bacterial pathogen during stressful conditions, supported by a reduction of plasma cortisol levels, an up-regulation of several immune-related genes at 48 h, and an inversion of the previously observed, stress-induced T-cell suppression. Finally, the involvement of tryptophan catabolism in macrophages was confirmed by the up-regulation of genes involved in the kynurenine pathway. The present study brings new insights regarding the immune modulatory role of tryptophan during stressful conditions in fish, thus allowing for the development of novel prophylactic protocols during vaccination by intraperitoneal injection in the European seabass. Full article
(This article belongs to the Special Issue Tryptophan in Nutrition and Health 3.0)
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Review

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26 pages, 1950 KiB  
Review
Microbiota, Tryptophan and Aryl Hydrocarbon Receptors as the Target Triad in Parkinson’s Disease—A Narrative Review
by Paulina Iwaniak, Maja Owe-Larsson and Ewa M. Urbańska
Int. J. Mol. Sci. 2024, 25(5), 2915; https://doi.org/10.3390/ijms25052915 - 2 Mar 2024
Cited by 6 | Viewed by 2507
Abstract
In the era of a steadily increasing lifespan, neurodegenerative diseases among the elderly present a significant therapeutic and socio-economic challenge. A properly balanced diet and microbiome diversity have been receiving increasing attention as targets for therapeutic interventions in neurodegeneration. Microbiota may affect cognitive [...] Read more.
In the era of a steadily increasing lifespan, neurodegenerative diseases among the elderly present a significant therapeutic and socio-economic challenge. A properly balanced diet and microbiome diversity have been receiving increasing attention as targets for therapeutic interventions in neurodegeneration. Microbiota may affect cognitive function, neuronal survival and death, and gut dysbiosis was identified in Parkinson’s disease (PD). Tryptophan (Trp), an essential amino acid, is degraded by microbiota and hosts numerous compounds with immune- and neuromodulating properties. This broad narrative review presents data supporting the concept that microbiota, the Trp-kynurenine (KYN) pathway and aryl hydrocarbon receptors (AhRs) form a triad involved in PD. A disturbed gut–brain axis allows the bidirectional spread of pro-inflammatory molecules and α-synuclein, which may contribute to the development/progression of the disease. We suggest that the peripheral levels of kynurenines and AhR ligands are strongly linked to the Trp metabolism in the gut and should be studied together with the composition of the microbiota. Such an approach can clearly delineate the sub-populations of PD patients manifesting with a disturbed microbiota–Trp-KYN–brain triad, who would benefit from modifications in the Trp metabolism. Analyses of the microbiome, Trp-KYN pathway metabolites and AhR signaling may shed light on the mechanisms of intestinal distress and identify new targets for the diagnosis and treatment in early-stage PD. Therapeutic interventions based on the combination of a well-defined food regimen, Trp and probiotics seem of potential benefit and require further experimental and clinical research. Full article
(This article belongs to the Special Issue Tryptophan in Nutrition and Health 3.0)
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24 pages, 763 KiB  
Review
Dietary Kynurenine Pathway Metabolites—Source, Fate, and Chromatographic Determinations
by Ilona Sadok and Katarzyna Jędruchniewicz
Int. J. Mol. Sci. 2023, 24(22), 16304; https://doi.org/10.3390/ijms242216304 - 14 Nov 2023
Cited by 4 | Viewed by 1800
Abstract
Tryptophan metabolism plays an essential role in human health. In mammals, about 95% of dietary tryptophan is metabolized through the kynurenine pathway, which is associated with the development of several pathologies, including neurodegeneration. Some of the kynurenine pathway metabolites are agonists of the [...] Read more.
Tryptophan metabolism plays an essential role in human health. In mammals, about 95% of dietary tryptophan is metabolized through the kynurenine pathway, which is associated with the development of several pathologies, including neurodegeneration. Some of the kynurenine pathway metabolites are agonists of the aryl hydrocarbon receptor involved in metabolic functions, inflammation, and carcinogenesis. Thus, their origins, fates, and roles are of widespread interest. Except for being produced endogenously, these metabolites can originate from exogenous sources (e.g., food) and undergo absorption in the digestive tract. Recently, a special focus on exogenous sources of tryptophan metabolites was observed. This overview summarizes current knowledge about the occurrence of the kynurenine pathway metabolites (kynurenines) in food and the analytical method utilized for their determination in different food matrices. Special attention was paid to sample preparation and chromatographic analysis, which has proven to be a core technique for the detection and quantification of kynurenines. A discussion of the fate and role of dietary kynurenines has also been addressed. This review will, hopefully, guide further studies on the impact of dietary kynurenines on human health. Full article
(This article belongs to the Special Issue Tryptophan in Nutrition and Health 3.0)
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