Tryptophan Metabolism Along the Kynurenine Pathway in Rats

Allegri, Graziella; Ragazzi, Eugenio; Bertazzo, Antonella; Costa, Carlo Virgilio Luigi; Rocchi, Raniero

doi:10.1007/978-1-4615-0135-0_56

Cited by 9 publications

(8 citation statements)

References 86 publications

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“…Tryptophan-tokynurenine transformation is one of the alternative tryptophan metabolic pathways, involved in the biosynthesis of NAD coenzyme from tryptophan (17). In rat, tryptophan is mainly metabolized along the kynurenine pathway (2). Our data showed that D3T inhibited the expression of kynureninase (Ϫ1.9-fold), the enzyme catalyzing the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids, respectively (1).…”

Section: Resultsmentioning

confidence: 88%

Identification of novel transcriptional networks in response to treatment with the anticarcinogen 3H-1,2-dithiole-3-thione

Huang

Yan

Lubet

et al. 2006

Physiological Genomics

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3H-1,2-dithiole-3-thione (D3T), an inducer of antioxidant and phase 2 genes, is known to enhance the detoxification of environmental carcinogens, prevent neoplasia, and elicit other protective effects. However, a comprehensive view of the regulatory pathways induced by this compound has not yet been elaborated. Fischer F344 rats were gavaged daily for 5 days with vehicle or D3T (0.3 mmol/kg). The global changes of gene expression in liver were measured with Affymetrix RG-U34A chips. With the use of functional class scoring, a semi-supervised method exploring both the expression pattern and the functional annotation of the genes, the Gene Ontology classes were ranked according to the significance of the impact of D3T treatment. Two unexpected functional classes were identified for the D3T treatment, cytosolic ribosome constituents with 90% of those genes increased, and cholesterol biosynthesis with 91% of the genes repressed. In another novel approach, the differentially expressed genes were evaluated by the Ingenuity computational pathway analysis tool to identify specific regulatory networks and canonical pathways responsive to D3T treatment. In addition to the known glutathione metabolism pathway (P = 0.0011), several other significant pathways were also revealed, including antigen presentation (P = 0.000476), androgen/estrogen biosynthesis (P = 0.000551), fatty acid (P = 0.000216), and tryptophan metabolism (P = 0.000331) pathways. These findings showed a profound impact of D3T on lipid metabolism and anti-inflammatory/immune-suppressive response, indicating a broader cytoprotective effect of this compound than previously expected.

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Section: Resultsmentioning

confidence: 88%

Identification of novel transcriptional networks in response to treatment with the anticarcinogen 3H-1,2-dithiole-3-thione

Huang

Yan

Lubet

et al. 2006

Physiological Genomics

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“…Abbreviations used: IDO, indoleamine 2,3-dioxygenase; hIDO, human IDO; TDO, tryptophan 2,3-dioxygenase; hTDO, human TDO. 1 To whom correspondence should be addressed (email emma.raven@le.ac.uk). [9], and yeast [10].…”

Section: Location and Isolation Of Tdo And Idomentioning

confidence: 98%

“…The kynurenine pathway converts L-tryptophan into NAD, which is responsible for the metabolism of the majority of Ltryptophan in biology ( Figure 1) [1]. The first, rate-limiting, step in this pathway is the formation of N-formylkynurenine by incorporation of dioxygen across the C 2 -C 3 bond of L-tryptophan ( Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Oxidation of L-tryptophan in biology: a comparison between tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase

Rafice

Chauhan

Efimov

et al. 2009

Biochemical Society Transactions

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The family of haem dioxygenases catalyse the initial oxidative cleavage of L-tryptophan to N-formylkynurenine, which is the first, rate-limiting, step in the L-kynurenine pathway. In the present paper, we discuss and compare structure and function across the family of haem dioxygenases by focusing on TDO (tryptophan 2,3-dioxygenase) and IDO (indoleamine 2,3-dioxygenase), including a review of recent structural information for both enzymes. The present paper describes how the recent development of recombinant expression systems has informed our more detailed understanding of the substrate binding, catalytic activity and mechanistic properties of these haem dioxygenases.

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“…Human astrocytes are unable to produce QUIN. However, non‐human astrocytes may be able to do so given the known inter‐species variation in KP enzyme expression [49,50,52,53,59–62]. There are conflicting results from several studies in mouse, rat, gerbil and human astrocytes and also between human primary astrocytes and astroglioma cell lines.…”

Section: What Is Known and What Is New About Quinolinic Acid Biosynthmentioning

confidence: 99%

Quinolinic acid, the inescapable neurotoxin

2012

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Over the last two decades, evidence for the involvement of quinolinic acid (QUIN) in neuroinflammatory diseases has been exponentially increasing. Within the brain, QUIN is produced and released by infiltrating macrophages and activated microglia, the very cells that are prominent during neuroinflammation. QUIN acts as an agonist of the N-methyl-D-aspartate receptor and as such is considered to be a brain endogenous excitotoxin. Since the discovery of the excitotoxic activity of QUIN in the early 1980s, several other cytotoxic mechanisms have been identified. We know today that QUIN acts as a neurotoxin, gliotoxin, proinflammatory mediator, prooxidant molecule and can alter the integrity and cohesion of the bloodbrain barrier. This paper aims to review some of the most recent findings about the effects of QUIN and its mode of action.

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Tryptophan Metabolism Along the Kynurenine Pathway in Rats

Cited by 9 publications

References 86 publications

Identification of novel transcriptional networks in response to treatment with the anticarcinogen 3H-1,2-dithiole-3-thione

Identification of novel transcriptional networks in response to treatment with the anticarcinogen 3H-1,2-dithiole-3-thione

Oxidation of L-tryptophan in biology: a comparison between tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase

Quinolinic acid, the inescapable neurotoxin

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