Kinurenin

l-Kinurenin
Općenito
Hemijski spojl-Kinurenin
Druga imena(S)-Kinurenin,
(2S)-2-Amino-4-(2-aminofenil)-4-okso-butanojska kiselina
Molekularna formulaC10H12N2O3
CAS registarski broj[http://www.nlm.nih.gov/cgi/mesh/2006/MB_cgi?term=343-65-7

CAS registarski broj-2: 2922-83-0
CAS registarski broj-3: 13441-51-5
&rn=1 343-65-7
CAS registarski broj-2: 2922-83-0

CAS registarski broj-3: 13441-51-5
]
InChI1S/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
Kratki opisMetabolit triptofana
Osobine1
Molarna masa20822 g mol−1
Agregatno stanjeČvrsto
Tačka topljenja
  • 191 °C, raspadanje [(S)-kinurenin]
  • 219 °C [(RS)-kinurenin]</small
1 Gdje god je moguće korištene su SI jedinice. Ako nije drugačije naznačeno, dati podaci vrijede pri standardnim uslovima.

l-Kinurenin je metabolit aminokiseline l-triptofan koja se koristi u proizvodnji niacina.

Kinurenin se sintetizira pomoću enzima triptofan-dioksigenaza, koji se proizvodi prvenstveno, ali ne isključivo u jetri, i indoleamin 2,3-dioksigenaza, koji se stvara u mnogim tkivima kao odgovor na imunsku aktivaciju.[1] Kinurenin i njegovi daljnji proizvodi razgradnje obavljaju različite biološke funkcije, uključujući širenje krvnih žila tokom upale[2] i reguliranje imunskog odgovora.[3] Neki karcinomi povećavaju proizvodnju kinurenina, što povećava rast tumora.[1]

Dokazi upućuju na to da povećana proizvodnja kinurenina može izazvati simptome depresije povezane s interferonom u liječenju hepatitisa C.[4] Kognitivni deficiti kod shizofrenije povezani su s neravnotežom enzima koji razgrađuju kinurenin.[5] Nivo kinurenina u krvi je smanjen kod ljudi sa bipolarnim poremećajem.[6] Proizvodnja kinurenina je povećana kod Alzhemerove[7] i kardiovaskularne bolesti,[8] gdje su njegovi metaboliti povezani sa kognitivnim deficitima [9] i simptomima depresije.[10] Kynurenine is also associated with tics.[11][12]

Kinureninaza katabolizira pretvorbu kinurenina u antranilnu kiselinu[13] dok kinurenin-oksoglutarat transaminaza katabolizira svoju konverziju u kinureninsku kiselinu. Kinurenin 3-hidroksilaza pretvara kinurenin u 3-hidroksikinurenin.[14]

Kinurenin je također identificiran kao jedan od dva spoja koji čine pigment koji daje žutu boju pauku Misumena vatia.[15]

Disfunkcija kinureninskog puta

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Disfunkcionalna stanja različitih koraka kinureninskog puta (kao što su kinurenin, kinurenska kiselina, kinolinska kiselina, antranilna kiselina, 3-hidroksikinurenin) opisana su za brojne poremećaje, uključujući:[16]

Podregulacija kinurenin-3-monooksigenaze (KMO) može biti uzrok genetičkim polimorfizmima, citokinima ili oboje.[19][20] Nedostatak KMO dovodi do akumulacije kinurenina i do pomaka unutar triptofanskog mwetabolučkog puta prema kinureninskoj i antranilnoj kiselini.[21] Nedostatak kinurenin-3-monooksigenaze povezan je s poremećajima mozga (npr. veliki depresivni poremećaj, bipolarni poremećaj, shizofrenija, tikovi) [22] and of the liver.[11][23][24][25][26]

Također pogledajte

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Reference

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  1. ^ 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. 478 (7368): 197–203. Bibcode:2011Natur.478..197O. doi:10.1038/nature10491. PMID 21976023.
  2. ^ Wang Y, Liu H, McKenzie G, Witting PK, Stasch JP, Hahn M, Changsirivathanathamrong D, Wu BJ, Ball HJ, Thomas SR, Kapoor V, Celermajer DS, Mellor AL, Keaney JF, Hunt NH, Stocker R (2010). "Kynurenine is an endothelium-derived relaxing factor produced during inflammation". Nature Medicine. 16 (3): 279–85. doi:10.1038/nm.2092. PMC 3556275. PMID 20190767.
  3. ^ Nguyen NT, Kimura A, Nakahama T, Chinen I, Masuda K, Nohara K, Fujii-Kuriyama Y, Kishimoto T (2010). "Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism". Proceedings of the National Academy of Sciences. 107 (46): 19961–6. Bibcode:2010PNAS..10719961N. doi:10.1073/pnas.1014465107. PMC 2993339. PMID 21041655.
  4. ^ Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, Miller AH (2003). "Interferon-alpha–induced changes in tryptophan metabolism". Biological Psychiatry. 54 (9): 906–14. doi:10.1016/S0006-3223(03)00173-2. PMID 14573318. S2CID 24079984.
  5. ^ Wonodi I, Stine OC, Sathyasaikumar KV, Roberts RC, Mitchell BD, Hong LE, Kajii Y, Thaker GK, Schwarcz R (2011). "Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme Activity in Schizophrenia and Genetic Association with Schizophrenia Endophenotypes". Archives of General Psychiatry. 68 (7): 665–74. doi:10.1001/archgenpsychiatry.2011.71. PMC 3855543. PMID 21727251.
  6. ^ a b Bartoli, F; Misiak, B; Callovini, T; Cavaleri, D; Cioni, RM; Crocamo, C; Savitz, JB; Carrà, G (19. 10. 2020). "The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites". Molecular Psychiatry. 26 (7): 3419–3429. doi:10.1038/s41380-020-00913-1. PMID 33077852. S2CID 224314102.
  7. ^ Guillemin GJ, Brew BJ, Noonan CE, Takikawa O, Cullen KM (2005). "Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus". Neuropathology and Applied Neurobiology. 31 (4): 395–404. doi:10.1111/j.1365-2990.2005.00655.x. PMID 16008823. S2CID 7754894.
  8. ^ Wirleitner B, Rudzite V, Neurauter G, Murr C, Kalnins U, Erglis A, Trusinskis K, Fuchs D (2003). "Immune activation and degradation of tryptophan in coronary heart disease". European Journal of Clinical Investigation. 33 (7): 550–4. doi:10.1046/j.1365-2362.2003.01186.x. PMID 12814390. S2CID 10300941.
  9. ^ Gulaj E, Pawlak K, Bien B, Pawlak D (2010). "Kynurenine and its metabolites in Alzheimer's disease patients". Advances in Medical Sciences. 55 (2): 204–11. doi:10.2478/v10039-010-0023-6. PMID 20639188.
  10. ^ Swardfager W, Herrmann N, Dowlati Y, Oh PI, Kiss A, Walker SE, Lanctôt KL (2009). "Indoleamine 2,3-dioxygenase activation and depressive symptoms in patients with coronary artery disease". Psychoneuroendocrinology. 34 (10): 1560–6. doi:10.1016/j.psyneuen.2009.05.019. PMID 19540675. S2CID 36687413.
  11. ^ a b Hoekstra PJ, Anderson GM, Troost PW, Kallenberg CG, Minderaa RB (2007). "Plasma kynurenine and related measures in tic disorder patients". European Child & Adolescent Psychiatry. 16: 71–7. doi:10.1007/s00787-007-1009-1. PMID 17665285. S2CID 39150343.
  12. ^ McCreary AC, Handley SL (1995). "Kynurenine potentiates the DOI head shake in mice". Journal of Psychopharmacology. 9 (1): 69–70. doi:10.1177/026988119500900112. PMID 22298697. S2CID 28700510.
  13. ^ Kynureninase, European Bioinformatics Institute
  14. ^ Saito Y, Hayaishi O, Rothberg S (1. 12. 1957). "Studies on Oxygenases". The Journal of Biological Chemistry. 229 (2): 921–34. doi:10.1016/S0021-9258(19)63696-3. PMID 13502353.
  15. ^ Oxford, G. S.; Gillespie, R. G. (januar 1998). "Evolution and Ecology of Spider Coloration". Annual Review of Entomology. 43 (1): 619–643. doi:10.1146/annurev.ento.43.1.619. ISSN 0066-4170. PMID 15012400.
  16. ^ Stone TW (2001). "Kynurenines in the CNS: from endogenous obscurity to therapeutic importance". Progress in Neurobiology. 64 (2): 185–218. doi:10.1016/s0301-0082(00)00032-0. PMID 11240212. S2CID 6446144.
  17. ^ Liu, Duan; Ray, Balmiki; Neavin, Drew R.; Zhang, Jiabin; Athreya, Arjun P.; Biernacka, Joanna M.; Bobo, William V.; Hall-Flavin, Daniel K.; Skime, Michelle K.; Zhu, Hongjie; Jenkins, Gregory D. (10. 1. 2018). "Beta-defensin 1, aryl hydrocarbon receptor and plasma kynurenine in major depressive disorder: metabolomics-informed genomics". Translational Psychiatry. 8 (1): 10. doi:10.1038/s41398-017-0056-8. ISSN 2158-3188. PMC 5802574. PMID 29317604.
  18. ^ Kashi, Alex A.; Davis, Ronald W.; Phair, Robert D. (2019). "The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS". Diagnostics. 9 (3): 82. doi:10.3390/diagnostics9030082. PMC 6787624. PMID 31357483.
  19. ^ "Neurobiochemie" (jezik: njemački).
  20. ^ Müller N, Myint AM, Schwarz MJ (2011). "Inflammatory biomarkers and depression". Neurotox Res. 19 (2): 308–18. doi:10.1007/s12640-010-9210-2. PMID 20658274. S2CID 3225744.
  21. ^ Wonodi I, Stine OC, Sathyasaikumar KV, Roberts RC, Mitchell BD, Hong LE, Kajii Y, Thaker GK, Schwarcz R (2011). "Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes". Arch. Gen. Psychiatry. 68 (7): 665–74. doi:10.1001/archgenpsychiatry.2011.71. PMC 3855543. PMID 21727251.
  22. ^ Marx W, McGuinness AJ, Rocks T, Ruusunen A, Cleminson J, Walker AJ, Gomes-da-Costa S, Lane M, Sanches M, Diaz AP, Tseng PT, Lin PY, Berk M, Clarke G, O'Neil A, Jacka F, Stubbs B, Carvalho AF, Quevedo J, Soares JC, Fernandes BS (2020). "The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies". Molecular Psychiatry. 26 (8): 4158–4178. doi:10.1038/s41380-020-00951-9. PMID 33230205. S2CID 227132820 – preko doi: 10.1038/s41380-020-00951-9. PMID 33230205.CS1 održavanje: više imena: authors list (link)
  23. ^ Holtze M, Saetre P, Engberg G, Schwieler L, Werge T, Andreassen OA, Hall H, Terenius L, Agartz I, Jönsson EG, Schalling M, Erhardt S (2012). "Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls". J Psychiatry Neurosci. 37 (1): 53–7. doi:10.1503/jpn.100175. PMC 3244499. PMID 21693093.
  24. ^ Campbell BM, Charych E, Lee AW, Möller T (2014). "Kynurenines in CNS disease: regulation by inflammatory cytokines". Front Neurosci. 8: 12. doi:10.3389/fnins.2014.00012. PMC 3915289. PMID 24567701.
  25. ^ Buness A, Roth A, Herrmann A, Schmitz O, Kamp H, Busch K, Suter L (2014). "Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity". PLOS ONE. 9 (5): e97249. Bibcode:2014PLoSO...997249B. doi:10.1371/journal.pone.0097249. PMC 4023975. PMID 24836604.
  26. ^ Hirata Y, Kawachi T, Sugimura T (1967). "Fatty liver induced by injection of L-tryptophan". Biochim. Biophys. Acta. 144 (2): 233–41. doi:10.1016/0005-2760(67)90153-1. PMID 4168935.

Vanjski linkovi

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Šablon:Intermedijari metabolizma aminokiselina Šablon:Modulatori ionotropnih glutamatnih receptora