Kynurenine 3-monooxygenase
| kynurenine 3-monooxygenase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 1.14.13.9 | ||||||||
| CAS number | 9029-61-2 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / EGO | ||||||||
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In enzymology, a kynurenine 3-monooxygenase (EC 1.14.13.9) is an enzyme that catalyzes the chemical reaction
- L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
The 4 substrates of this enzyme are L-kynurenine, NADPH, H+, and O2, whereas its 3 products are 3-hydroxy-L-kynurenine, NADP+, and H2O. Kynurenine 3-monooxygenase is the expression product of the KMO (gene).
This enzyme belongs to the family of oxidoreductases, to be specific, those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor. The systematic name of this enzyme class is L-kynurenine,NADPH:oxygen oxidoreductase (3-hydroxylating). Other names in common use include kynurenine 3-hydroxylase, kynurenine hydroxylase, and L-kynurenine-3-hydroxylase. This enzyme participates in tryptophan metabolism. It employs one cofactor, FAD.
Kynurenine-3-monooxygenase deficiency
Downregulation of kynurenine-3-monooxygenase (KMO) can be caused by genetic polymorphisms, cytokines, or both.[1][2] KMO deficiency leads to an accumulation of kynurenine and to a shift within the tryptophan metabolic pathway towards kynurenine acid and anthranilic acid.[3] Kynurenine-3-monooxygenase deficiency is associated with disorders of the brain (e.g. schizophrenia, tic disorders) and of the liver.[4][5][6][7][8]
References
- ↑ http://www.klinikum.uni-muenchen.de/Institut-fuer-Laboratoriumsmedizin/de/forschung/neurobiochemie/index.html (Website in German). Retrieved 26 May 2014
- ↑ Müller N, Myint AM, Schwarz MJ: (2010) Inflammatory Biomarkers and Depression. Neurotox Res. 19: 308-318.
- ↑ Ikwunga Wonodi, MD; O. Colin Stine, PhD; Korrapati V. Sathyasaikumar, et al., : Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme Activity in Schizophrenia and Genetic Association With Schizophrenia Endophenotypes. Arch Gen Psychiatry. 2011;68(7):665-674
- ↑ Maria Holtze, MSc, Peter Saetre, PhD, Göran Engberg, et al.: Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls. J Psychiatry Neurosci. Jan 2012; 37(1): 53–57.
- ↑ Brian M.Campbell, Erik Charych,Anna W. Lee, Thomas Möller: Kynurenines in CNS disease: regulation byinflammatory cytokines. Frontiers in Neuroscience. Neuroendocrine Science February 2014, Volume 8, Article 12.
- ↑ Hoekstra PJ, Anderson GM, Troost PW: Plasma kynurenine and related measures in tic disorder patients. Eur Child Adolesc Psychiatry. 2007 Jun;16 Suppl 1:71-7.
- ↑ Buness A, Roth A, Herrmann A, Schmitz O, Kamp H, et al. (2014) Identification of Metabolites, Clinical Chemistry Markers and Transcripts Associated with Hepatotoxicity. PLoS ONE 9(5): e97249. doi:10.1371/journal.pone.0097249
- ↑ Hirata Yukiko, Kawachi Takashi, Sugimura Takashi: Fatty liver induced by injection of L-tryptophan. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. Volume 144, Issue 2, 2 October 1967, Pages 233–241.
- Foucher AL, McIntosh A, Douce G, Wastling J, Tait A, Turner CM (2006). "A proteomic analysis of arsenical drug resistance in Trypanosoma brucei". Proteomics. 6 (9): 2726–32. doi:10.1002/pmic.200500419. PMID 16526094.
- Okamoto H, Hayaishi O (1967). "Flavin adenine dinucleotide requirement for kynurenine hydroxylase of rat liver mitochondria". Biochem. Biophys. Res. Commun. 29 (3): 394–9. doi:10.1016/0006-291X(67)90469-X. PMID 6076241.
- 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.