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Focus on the Tryptophan Pathway
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Focus on the Tryptophan Pathway

A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Molecular Biology".

Deadline for manuscript submissions: 30 October 2026 | Viewed by 3703

Editor

Prof. Dr. Burkhard Poeggeler

E-Mail Website
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, Gütersloh D-33332, 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 a unique building block of peptides and proteins. This amino acid serves as the precursor for important endogenous indoleamines such as serotonin, N-acetylserotonin, and melatonin, which act as neurotransmitters, neuromodulators, and neurohormones. The enhanced synthesis of these potent endogenous signaling molecules can improve health, quality of life, and well-being. A tryptophan-enriched diet may be considered a component of the treatment of elderly individuals to improve cognition, mood, and health. The main metabolic pathway of tryptophan is the oxidation to bioactive kynurenines and niacin. Kynurenic acid is the most potent endogenous anti-exitotoxic agent. Other highly relevant pathways of tryptophan are the reversible transamination to indole-3-pyruvate with the formation of related indolic acids and amides, as well as the synthesis of indole compounds and their derivatives through side chain cleavage. Indolic acids and amides, such as indole-3-propionic acid and indole-3-propionamide, act as potent protective antioxidant agents, whereas indoles such as indole, indoxyl, and indoxyl sulfate are reactive compounds that are primarily studied because of their potential toxicity.

Dr. Burkhard Poeggeler
Guest Editor

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Keywords

  • aging
  • indole-3-propionic acid
  • kynurenic acid
  • melatonin
  • serotonin
  • tryptophan

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Published Papers (2 papers)

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15 pages, 2045 KB  
Article
Monochromatic Photophase Light Alters Diurnal Profiles of Melatonin Pathway Indoles in the Rat Pineal Gland
by Bogdan Lewczuk, Kamila Martyniuk, Natalia Szyryńska, Magdalena Prusik and Natalia Ziółkowska
Int. J. Mol. Sci. 2025, 26(13), 6515; https://doi.org/10.3390/ijms26136515 - 6 Jul 2025
Cited by 2 | Viewed by 2059
Abstract
Light is a major environmental factor that regulates circadian rhythms and pineal melatonin synthesis. While the influence of nighttime light exposure on melatonin suppression has been extensively investigated, much less is known about the impact of photophase light wavelength on pineal function. The [...] Read more.
Light is a major environmental factor that regulates circadian rhythms and pineal melatonin synthesis. While the influence of nighttime light exposure on melatonin suppression has been extensively investigated, much less is known about the impact of photophase light wavelength on pineal function. The aim of the study was to determine the influence of monochromatic light during the photophase on diurnal changes in melatonin-related indoles in the rat pineal gland. Wistar rats were exposed for 7 days to 150 lx of monochromatic blue (463 ± 10 nm), green (523 ± 10 nm), or red (623 ± 10 nm) LED light, or to white fluorescent light (control), under a 12:12 light–dark cycle. Pineal glands were collected every 3 h over 24 h, and the indole content was analyzed by high-performance liquid chromatography. The results demonstrated that both the timing and course of N-acetylserotonin (NAS) and melatonin (MLT) rhythms were significantly affected by light wavelength. Blue light most effectively preserved the normal rhythmicity observed under full-spectrum white light, whereas green—and particularly red light—delayed nocturnal NAS and MLT synthesis. These changes were accompanied by concurrent alternations in rhythms of serotonin, its precursors, and metabolites. The data strongly suggest that spectral light composition during the photophase influences pineal indole metabolism via melanopsin-mediated phototransduction and possibly other retinal mechanisms. These findings may have implications for the design of artificial lighting environments in human life and animal housing. Full article
(This article belongs to the Special Issue Focus on the Tryptophan Pathway)
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Review

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32 pages, 1628 KB  
Review
Tryptophan Metabolism in Cardiometabolic Diseases: Focus on the Kynurenine Pathway
by Shafaat Hussain, Mohamed M. Bekhite and P. Christian Schulze
Int. J. Mol. Sci. 2026, 27(12), 5223; https://doi.org/10.3390/ijms27125223 - 9 Jun 2026
Viewed by 850
Abstract
Tryptophan (TRP) metabolism has emerged as a critical interface linking inflammation, immune regulation, oxidative stress, and cellular energetics. The kynurenine pathway, the predominant route of TRP degradation, is highly responsive to inflammatory stimuli and generates a spectrum of bioactive metabolites with divergent and [...] Read more.
Tryptophan (TRP) metabolism has emerged as a critical interface linking inflammation, immune regulation, oxidative stress, and cellular energetics. The kynurenine pathway, the predominant route of TRP degradation, is highly responsive to inflammatory stimuli and generates a spectrum of bioactive metabolites with divergent and context-dependent biological effects. Indoleamine 2,3-dioxygenase 1 (IDO1)-mediated TRP catabolism integrates immune activation with downstream metabolic signaling, influencing redox homeostasis, endothelial function, and mitochondrial energetics, in part by regulating nicotinamide adenine dinucleotide (NAD+) synthesis. Alterations in TRP metabolism are consistently observed across cardiometabolic diseases, including obesity, type 2 diabetes (T2D), atherosclerosis, myocardial infarction (MI), and heart failure with preserved ejection fraction (HFpEF), where they are associated with disease severity and adverse outcomes. Importantly, emerging data suggest that cardiometabolic phenotypes are determined not by pathway activation alone, but by the relative distribution of flux across downstream metabolic branches. Depending on the tissue compartment and stage of the disease, different biological effects may be contributed by redox-active kynurenine 3-monooxygenase (KMO)/3-hydroxykynurenine (3-HK)/quinolinic acid (QA) pathways, 3-hydroxyanthranilic acid (3-HAA)-mediated lipid and inflammasome regulation, microbiome-derived indoles, and NAD+-generating pathways. This review synthesizes current evidence using a branch-specific and context-dependent framework. We discuss the utility and limitations of the kynurenine-to-tryptophan ratio (KTR) as an upstream biomarker, the need for downstream metabolite panels, and therapeutic opportunities aimed at pathway modulation rather than broad inhibition. Future studies integrating temporal profiling, spatial and cell-specific approaches, large-animal models, and pathway-informed clinical trials will be essential to define causal mechanisms and enable precision therapeutic translation. Full article
(This article belongs to the Special Issue Focus on the Tryptophan Pathway)
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