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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/10 19:55:44」(JST)

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L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.^[1]^[2]

The primary product of the liver enzyme tryptophan dioxygenase is kynurenine.^[3] Cancers upregulate tryptophan dioxygenase because kynurenine increases tumor growth.^[3].

Kynureninase catabolizes the conversion of kynurenine into anthranilic acid^[4] while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid. Kynurenine 3-hydroxylase converts kynurenine to 3-hydroxykynurenine.^[5]

References

^ Hoekstra PJ, Anderson GM, Troost PW, Kallenberg CG, Minderaa RB (June 2007). "Plasma kynurenine and related measures in tic disorder patients". European Child & Adolescent Psychiatry 16 Suppl 1: 71–7. doi:10.1007/s00787-007-1009-1. PMID 17665285.
^ "Kynurenine potentiates the DOI head shake in mice | DeepDyve - Research. Rent. Read.". http://www.deepdyve.com/lp/sage/kynurenine-potentiates-the-doi-head-shake-in-mice-VcC8uCOwXw. Retrieved 2011-04-06.
^ ^a ^b Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, Schumacher T, Jestaedt L, Schrenk D, Weller M, Jugold M, Guillemin GJ, Miller CL, Lutz C, Radlwimmer B, Lehmann I, von Deimling A, Wick W, Platten M (2011). "An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor". Nature (journal) 478 (7368): 197–203. doi:10.1038/nature10491. PMID 21976023.
^ Kynureninase, European Bioinformatics Institute
^ Saito, Y., Hayaishi, O., Rothberg, S. (1957). "Studies on oxygenases; enzymatic formation of 3-hydroxy-L-kynurenine from L-kynurenine". J. Biol. Chem. 229 (2): 921–34. PMID 13502353.

UpToDate Contents

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1. 慢性肉芽腫性疾患：病因、臨床症状、および診断 chronic granulomatous disease pathogenesis clinical manifestations and diagnosis
2. 癌免疫療法の原則 principles of cancer immunotherapy

English Journal

Antitumour agents as inhibitors of tryptophan 2,3-dioxygenase.

Pantouris G1, Mowat CG2.Author information 1EaStCHEM School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK.2EaStCHEM School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK. Electronic address: C.G.Mowat@ed.ac.uk.AbstractThe involvement of tryptophan 2,3-dioxygenase (TDO) in cancer biology has recently been described, with the enzyme playing an immunomodulatory role, suppressing antitumour immune responses and promoting tumour cell survival and proliferation. This finding reinforces the need for specific inhibitors of TDO that may potentially be developed for therapeutic use. In this work we have screened ∼2800 compounds from the library of the National Cancer Institute USA and identified seven potent inhibitors of TDO with inhibition constants in the nanomolar or low micromolar range. All seven have antitumour properties, killing various cancer cell lines. For comparison, the inhibition potencies of these compounds were tested against IDO and their inhibition constants are reported. Interestingly, this work reveals that NSC 36398 (dihydroquercetin, taxifolin), with an in vitro inhibition constant of ∼16μM, is the first TDO-selective inhibitor reported.
Biochemical and biophysical research communications.Biochem Biophys Res Commun.2014 Jan 3;443(1):28-31. doi: 10.1016/j.bbrc.2013.11.037. Epub 2013 Nov 19.
The involvement of tryptophan 2,3-dioxygenase (TDO) in cancer biology has recently been described, with the enzyme playing an immunomodulatory role, suppressing antitumour immune responses and promoting tumour cell survival and proliferation. This finding reinforces the need for specific inhibitors
PMID 24269239

Peripheral immunomodulation with ginsenoside Rg1 ameliorates neuroinflammation-induced behavioral deficits in rats.

Zheng X1, Liang Y2, Kang A3, Ma SJ2, Xing L2, Zhou YY2, Dai C2, Xie H2, Xie L2, Wang GJ4, Hao HP5.Author information 1State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, PR China; Department of Pharmaceutical Preparation, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, PR China.2State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, PR China.3State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.4State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: guangjiwang@hotmail.com.5State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: hhp_770505@yahoo.com.cn.AbstractNeuroinflammatory disturbances have been closely associated with depression and many other neuropsychiatric diseases. Although targeting neuroinflammatory mediators with centrally acting drugs has shown certain promise, its translation is faced with several challenges especially drug delivery and safety concerns. Here, we report that neuroinflammation-induced behavioral abnormality could be effectively attenuated with immunomodulatory agents that need not to gain brain penetration. In a rat model with intracerebral lipopolysaccharide (LPS) challenge, we validated that ginsenoside Rg1 (Rg1), a well-established anti-inflammatory agent, was unable to produce a direct action in the brain. Interestingly, peripherally restricted Rg1 could effectively attenuate the weight loss, anorexic- and depressive-like behavior as well as neurochemical disturbances associated with central LPS challenge. Biochemical assay of neuroimmune mediators in the periphery revealed that Rg1 could mitigate the deregulation of the hypothalamic-pituitary-adrenal axis and selectively blunt the increase in circulating interleukin-6 levels. Furthermore, these peripheral regulatory effects were accompanied by dampened microglial activation, mitigated expression of pro-inflammatory mediators and neurotoxic species in the central compartment. Taken together, our work suggested that targeting the peripheral immune system may serve as a novel therapeutic approach to neuroinflammation-induced neuropsychiatric disorders. Moreover, our findings provided the rationale for employing peripherally active agents like Rg1 to combat mental disturbances.
Neuroscience.Neuroscience.2014 Jan 3;256:210-22. doi: 10.1016/j.neuroscience.2013.10.023. Epub 2013 Oct 23.
Neuroinflammatory disturbances have been closely associated with depression and many other neuropsychiatric diseases. Although targeting neuroinflammatory mediators with centrally acting drugs has shown certain promise, its translation is faced with several challenges especially drug delivery and sa
PMID 24161284

Network beyond IDO in psychiatric disorders: Revisiting neurodegeneration hypothesis.

Myint AM, Kim YK.Author information Psychiatric Hospital, Ludwig Maximilian University, Nussbaumstrasse 7; D-80336 Munich, Germany; School for Mental Health and Neuroscience, Maastricht University, The Netherlands. Electronic address: AyeMu.Myint@med.uni-muenchen.de.AbstractThe involvement of immune system activation in the pathophysiology of certain psychiatric disorders is well documented. Inflammatory molecules such as pro-inflammatory cytokines could enhance the activity of the indoleamine 2,3-dioxygenase (IDO) enzyme which is the first rate-limiting enzyme of the tryptophan degradation pathway, the kynurenine pathway. The increased tryptophan degradation could induce serotonin depletion and depressive mood. On the other hand, the downstream metabolites from this pathway, such as 3-hydroxykynurenine, quinolinic acid and kynurenic acid, are neuroactive metabolites which can modulate several neurotransmissions, such as glutamatergic, GABAergic, dopaminergic and noradrenergic neurotransmissions, which in turn induce changes in neuronal-glial network and neuropsychiatric consequences. In this issue, we have revised the previous 'neurodegeneration hypothesis,' which explained the involvement of cytokines and IDO pathway interaction in depression, with a further extended view related to the network beyond IDO, the network between immune molecules, tryptophan metabolites and different neurotransmitters, in depression and other major psychiatric disorders such as schizophrenia, bipolar disorder and childhood psychiatric disorders.
Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2014 Jan 3;48:304-13. doi: 10.1016/j.pnpbp.2013.08.008. Epub 2013 Oct 31.
The involvement of immune system activation in the pathophysiology of certain psychiatric disorders is well documented. Inflammatory molecules such as pro-inflammatory cytokines could enhance the activity of the indoleamine 2,3-dioxygenase (IDO) enzyme which is the first rate-limiting enzyme of the
PMID 24184687

Japanese Journal

Time-Dependent Effects of L-Tryptophan Administration on Urinary Excretion of L-Tryptophan Metabolites

HIRATSUKA Chiaki,SANO Mitsue,FUKUWATARI Tsutomu [他]
Journal of nutritional science and vitaminology 60(4), 255-260, 2014-08
NAID 40020173432

Time-Dependent Effects of L-Tryptophan Administration on Urinary Excretion of L-Tryptophan Metabolites

HIRATSUKA Chiaki,SANO Mitsue,FUKUWATARI Tsutomu,SHIBATA Katsumi
Journal of Nutritional Science and Vitaminology 60(4), 255-260, 2014
… L-Trp doses had weak effects on the urinary excretion of kynurenine and anthranilic acid. …
NAID 130004695717

Evaluation of human D-amino acid oxidase inhibition by anti-psychotic drugs in vitro

Shishikura Miho,Hakariya Hitomi,Iwasa Sumiko,Yoshio Takashi,Ichiba Hideaki,Yorita Kazuko,Fukui Kiyoshi,Fukushima Takeshi
BioScience Trends 8(3), 149-154, 2014
… We first investigated whether human (h)DAO can metabolize D-kynurenine (D-KYN) to produce the fluorescent compound kynurenic acid (KYNA) by using high-performance liquid chromatography with mass spectrometry, and fluorescence spectrometry. …
NAID 130004572599

「キヌレニン」

Kynurenine
	IUPAC name (S)-2-Amino-4-(2-aminophenyl)- 4-oxo-butanoic acid
	Other names (S)-Kynurenine
Identifiers
CAS number	343-65-7 , (D/L); 2922-83-0 (L); 13441-51-5 (D)
PubChem	846
ChemSpider	141580
DrugBank	DB02070
MeSH	Kynurenine
ChEBI	CHEBI:57959
ChEMBL	CHEMBL498416
Jmol-3D images	Image 1
	SMILES C1=CC=C(C(=C1)C(=O)CC(C(=O)O)N)N ;
	InChI InChI=1S/C10H12N2O3/c11-7-4-2-1-3-6(7)9(13)5-8(12)10(14)15/h1-4,8H,5,11-12H2,(H,14,15)/t8-/m0/s1 ; Key: YGPSJZOEDVAXAB-QMMMGPOBSA-N ;
Properties
Molecular formula	C10H12N2O3
Molar mass	208.21 g mol−1
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references