Tryptophan in health and disease

Comai, Stefano; Bertazzo, Antonella; Brughera, Martina; Crotti, Sara

doi:10.1016/bs.acc.2019.08.005

Cited by 168 publications

(149 citation statements)

References 239 publications

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“…These findings highlight the potential regulatory activity for TRP and its metabolites on the secretory, motor, and sensory gut functions in health and disease conditions. The effects of TRP metabolites are, however, not only confined to the regulation of cell homeostasis within the enteric microenvironment, but may also extend to the CNS, influencing mood and cognitive functions 23,29,30 . This latter observation lends itself to the possibility of studying the involvement of tryptophan metabolites in the generation of microbiota‐gut‐brain axis signaling underlying psychiatric disturbances associated with IBS 23,30 .…”

Section: Introductionmentioning

confidence: 99%

Oxidized phospholipids affect small intestine neuromuscular transmission and serotonergic pathways in juvenile mice

Marsilio

Caputi

Latorre

et al. 2020

Neurogastroenterology Motil

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Background Oxidized phospholipid derivatives (OxPAPCs) act as bacterial lipopolysaccharide (LPS)–like damage‐associated molecular patterns. OxPAPCs dose‐dependently exert pro‐ or anti‐inflammatory effects by interacting with several cellular receptors, mainly Toll‐like receptors 2 and 4. It is currently unknown whether OxPAPCs may affect enteric nervous system (ENS) functional and structural integrity. Methods Juvenile (3 weeks old) male C57Bl/6 mice were treated intraperitoneally with OxPAPCs, twice daily for 3 days. Changes in small intestinal contractility were evaluated by isometric neuromuscular responses to receptor and non–receptor‐mediated stimuli. Alterations in ENS integrity and serotonergic pathways were assessed by real‐time PCR and confocal immunofluorescence microscopy in longitudinal muscle‐myenteric plexus whole‐mount preparations (LMMPs). Tissue levels of serotonin (5‐HT), tryptophan, and kynurenine were measured by HPLC coupled to UV/fluorescent detection. Key Results OxPAPC treatment induced enteric gliosis, loss of myenteric plexus neurons, and excitatory hypercontractility, and reduced nitrergic neurotransmission with no changes in nNOS+ neurons. Interestingly, these changes were associated with a higher functional response to 5‐HT, altered immunoreactivity of 5‐HT receptors and serotonin transporter (SERT) together with a marked decrease in 5‐HT levels, shifting tryptophan metabolism toward kynurenine production. Conclusions and Inferences OxPAPC treatment disrupted structural and functional integrity of the ENS, affecting serotoninergic tone and 5‐HT tissue levels toward a higher kynurenine content during adolescence, suggesting that changes in intestinal lipid metabolism toward oxidation can affect serotoninergic pathways, potentially increasing the risk of developing functional gastrointestinal disorders during critical stages of development.

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Section: Introductionmentioning

confidence: 99%

Oxidized phospholipids affect small intestine neuromuscular transmission and serotonergic pathways in juvenile mice

Marsilio

Caputi

Latorre

et al. 2020

Neurogastroenterology Motil

Self Cite

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“…The biomedical literature contains extensive information about the diversity and key roles of exposed and buried Trp residues both in protein-and enzyme-associated acquired and innate illnesses, and in signal transduction (36,37). Given the participation of Trp in a multitude of biological and photochemical processes driven by radicals and 1 O 2 , this work focuses on the mechanism of Trp interference in the enzymatic generation of a model of excited carbonyl, namely Ac 3* .…”

Section: Resultsmentioning

confidence: 99%

l‐Tryptophan Interactions with the Horseradish Peroxidase‐Catalyzed Generation of Triplet Acetone

Ramos

Prado

Stevani

et al. 2021

Photochem & Photobiology

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Triplet carbonyls generated by chemiexcitation are involved in typical photobiochemical processes in the absence of light. Due to their biradical nature, ultraweak light emission and long lifetime, electronically excited triplet species display typical radical reactions such as isomerization, fragmentation, cycloaddition and hydrogen abstraction. In this paper, we report chemical reactions in a set of amino acid residues induced by the isobutanal/horseradish peroxidase (IBAL/HRP) system, a well‐known source of excited triplet acetone (Ac3*). Accordingly, quenching of Ac3* by tryptophan (Trp) unveiled parallel enzyme damage and inactivation, likely explained by scavenging of IBAL tertiary radical reaction intermediate and Ac3*‐derived 2‐hydroxy‐i‐propyl radical. Quenching constants were calculated from Stern–Volmer plots, and the structure of radical adducts was revealed by mass spectrometry. As expected, a concurrent Schiff‐type adduct was found to be one of the reaction by‐products. These findings draw attention to potential structural and functional changes in enzymes involved in the electronic chemiexcitation of their products.

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“…Most of the TRP in plasma is bound to albumin. Under normal physiological conditions the free TRP portion accounts for 10-15% of total TRP as shown by more recent research (16). The free TRP portion is available for transport into the central nervous system (CNS).…”

Section: Acute Tryptophan Depletion and The Development Of The Moja-dmentioning

confidence: 99%

Acute Tryptophan Depletion Moja-De: A Method to Study Central Nervous Serotonin Function in Children and Adolescents

et al. 2020

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Serotonin (5-HT) is widely implicated as a key neurotransmitter relevant to a range of psychiatric disorders and psychological processes. The role of central nervous 5-HT function underlying these processes can be examined through serotonergic challenge methodologies. Acute tryptophan depletion (ATD) is a key challenge method whereby a diminished dietary intake of tryptophan-the amino acid precursor to brain 5-HT synthesis-results in temporary diminished central nervous 5-HT synthesis. While this particular methodology has been used in adult populations, it was only recently that modifications were made to enable the use of ATD in child and adolescent populations. Additionally, the Moja-De modification of the ATD challenge methodology has demonstrated benefits over other ATD techniques used previously. The aim of this protocol paper is to describe the ATD Moja-De methodology in detail, its benefits, as well as studies that have been conducted to validate the procedure in child and adolescent samples. The ATD Moja-De protocol provides a potential methodology for investigating the role of central nervous 5-HT via manipulation of brain tryptophan availability in human psychopathology from a developmental viewpoint.

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Tryptophan in health and disease

Cited by 168 publications

References 239 publications

Oxidized phospholipids affect small intestine neuromuscular transmission and serotonergic pathways in juvenile mice

Oxidized phospholipids affect small intestine neuromuscular transmission and serotonergic pathways in juvenile mice

l‐Tryptophan Interactions with the Horseradish Peroxidase‐Catalyzed Generation of Triplet Acetone

Acute Tryptophan Depletion Moja-De: A Method to Study Central Nervous Serotonin Function in Children and Adolescents

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