Indoleamine 2,3-dioxygenase
Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO EC 1.13.11.52) is an enzyme that in humans is encoded by the IDO1 gene.[1][2] This enzyme catalyzes the degradation of the essential amino acid L-tryptophan to N-formylkynurenine.[3]
Function
Indoleamine 2,3-dioxygenase is the first and rate-limiting enzyme of tryptophan catabolism through kynurenine pathway, thus causing depletion of tryptophan which can cause halted growth of microbes as well as T cells.
INDO is an immunomodulatory enzyme produced by some alternatively activated macrophages and other immunoregulatory cells (also used as an immune subversion strategy by many tumors). INDO Interferon-gamma has an antiproliferative effect on many tumor cells and inhibits intracellular pathogens such as Toxoplasma and chlamydia, at least partly because of the induction of indoleamine 2,3-dioxygenase.
Inhibitors
Norharmane, via inhibition of indoleamine 2,3-dioxygenase exerts neuroprotective properties by suppressing kynurenine neurotoxic metabolites such as quinolinic acid, 3-hydroxy-kynurenine and nitric oxide synthase.[4] Rosmarinic acid inhibits the expression of indoleamine 2,3-dioxygenase via it's cyclooxygenase inhibiting properties.[5] COX-2 inhibitors down-regulate indoleamine 2,3-dioxygenase, leading to a reduction in kynurenine levels as well as reducing proinflammatory cytokine activity.[6]
See also
1-Methyltryptophan
Tryptophan 2,3-dioxygenase
References
- ^ Dai W, Gupta SL (April 1990). "Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA". Biochem. Biophys. Res. Commun. 168 (1): 1–8. doi:10.1016/0006-291X(90)91666-G. PMID 2109605.
- ^ Najfeld V, Menninger J, Muhleman D, Comings DE, Gupta SL (1993). "Localization of indoleamine 2,3-dioxygenase gene (INDO) to chromosome 8p12-->p11 by fluorescent in situ hybridization". Cytogenet. Cell Genet. 64 (3–4): 231–2. doi:10.1159/000133584. PMID 8404046.
- ^ "Entrez Gene: INDO indoleamine-pyrrole 2,3 dioxygenase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3620.
- ^ Chiarugi A, Dello Sbarba P, Paccagnini A, Donnini S, Filippi S, Moroni F (August 2000). "Combined inhibition of indoleamine 2,3-dioxygenase and nitric oxide synthase modulates neurotoxin release by interferon-gamma-activated macrophages". J. Leukoc. Biol. 68 (2): 260–6. PMID 10947071. http://www.jleukbio.org/content/68/2/260.long.
- ^ Lee HJ, Jeong YI, Lee TH, et al. (May 2007). "Rosmarinic acid inhibits indoleamine 2,3-dioxygenase expression in murine dendritic cells". Biochem. Pharmacol. 73 (9): 1412–21. doi:10.1016/j.bcp.2006.12.018. PMID 17229401.
- ^ Cesario A, Rocca B, Rutella S (2011). "The interplay between indoleamine 2,3-dioxygenase 1 (IDO1) and cyclooxygenase (COX)-2 in chronic inflammation and cancer". Curr. Med. Chem. 18 (15): 2263–71. PMID 21517752.
Further reading
- Grohmann U, Fallarino F, Puccetti P (2004). "Tolerance, DCs and tryptophan: much ado about IDO". Trends Immunol. 24 (5): 242–8. doi:10.1016/S1471-4906(03)00072-3. PMID 12738417.
- Takikawa O (2005). "Biochemical and medical aspects of the indoleamine 2,3-dioxygenase-initiated L-tryptophan metabolism". Biochem. Biophys. Res. Commun. 338 (1): 12–9. doi:10.1016/j.bbrc.2005.09.032. PMID 16176799.
- Puccetti P (2007). "On watching the watchers: IDO and type I/II IFN". Eur. J. Immunol. 37 (4): 876–9. doi:10.1002/eji.200737184. PMID 17393386.
- Kadoya A, Tone S, Maeda H, et al. (1992). "Gene structure of human indoleamine 2,3-dioxygenase". Biochem. Biophys. Res. Commun. 189 (1): 530–6. doi:10.1016/0006-291X(92)91590-M. PMID 1449503.
- Kamimura S, Eguchi K, Yonezawa M, Sekiba K (1991). "Localization and developmental change of indoleamine 2,3-dioxygenase activity in the human placenta". Acta Med. Okayama 45 (3): 135–9. PMID 1716396.
- Tone S, Takikawa O, Habara-Ohkubo A, et al. (1990). "Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA". Nucleic Acids Res. 18 (2): 367. doi:10.1093/nar/18.2.367. PMC 330282. PMID 2326172. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=330282.
- Werner-Felmayer G, Werner ER, Fuchs D, et al. (1990). "Tumour necrosis factor-alpha and lipopolysaccharide enhance interferon-induced tryptophan degradation and pteridine synthesis in human cells". Biol. Chem. Hoppe-Seyler 370 (9): 1063–9. PMID 2482041.
- Carlin JM, Borden EC, Byrne GI (1989). "Interferon-induced indoleamine 2,3-dioxygenase activity inhibits Chlamydia psittaci replication in human macrophages". J. Interferon Res. 9 (3): 329–37. doi:10.1089/jir.1989.9.329. PMID 2501398.
- Kobayashi K, Hayashi K, Sono M (1989). "Effects of tryptophan and pH on the kinetics of superoxide radical binding to indoleamine 2,3-dioxygenase studied by pulse radiolysis". J. Biol. Chem. 264 (26): 15280–3. PMID 2549057.
- Daley-Yates PT, Powell AP, Smith LL (1989). "Pulmonary indoleamine 2,3-dioxygenase activity and its significance in the response of rats, mice, and rabbits to oxidative stress". Toxicol. Appl. Pharmacol. 96 (2): 222–32. doi:10.1016/0041-008X(88)90082-8. PMID 2848333.
- Burkin DJ, Kimbro KS, Barr BL, et al. (1993). "Localization of the human indoleamine 2,3-dioxygenase (IDO) gene to the pericentromeric region of human chromosome 8". Genomics 17 (1): 262–3. doi:10.1006/geno.1993.1319. PMID 8406467.
- Malina HZ, Martin XD (1996). "Indoleamine 2,3-dioxygenase: antioxidant enzyme in the human eye". Graefes Arch. Clin. Exp. Ophthalmol. 234 (7): 457–62. doi:10.1007/BF02539413. PMID 8817290.
- Munn DH, Zhou M, Attwood JT, et al. (1998). "Prevention of allogeneic fetal rejection by tryptophan catabolism". Science 281 (5380): 1191–3. doi:10.1126/science.281.5380.1191. PMID 9712583.
- Takikawa O, Littlejohn TK, Truscott RJ (2001). "Indoleamine 2,3-dioxygenase in the human lens, the first enzyme in the synthesis of UV filters". Exp. Eye Res. 72 (3): 271–7. doi:10.1006/exer.2000.0951. PMID 11180976.
- Kudo Y, Boyd CA (2001). "The role of l-tryptophan transport in l-tryptophan degradation by indoleamine 2,3-dioxygenase in human placental explants". J. Physiol. (Lond.) 531 (Pt 2): 417–23. doi:10.1111/j.1469-7793.2001.0417i.x. PMC 2278460. PMID 11230514. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2278460.
- Terentis AC, Thomas SR, Takikawa O, et al. (2002). "The heme environment of recombinant human indoleamine 2,3-dioxygenase. Structural properties and substrate-ligand interactions". J. Biol. Chem. 277 (18): 15788–94. doi:10.1074/jbc.M200457200. PMID 11867636.
- Kvirkvelia N, Vojnovic I, Warner TD, et al. (2002). "Placentally derived prostaglandin E2 acts via the EP4 receptor to inhibit IL-2-dependent proliferation of CTLL-2 T cells". Clin. Exp. Immunol. 127 (2): 263–9. doi:10.1046/j.1365-2249.2002.01718.x. PMC 1906325. PMID 11876748. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1906325.
- Sedlmayr P, Blaschitz A, Wintersteiger R, et al. (2002). "Localization of indoleamine 2,3-dioxygenase in human female reproductive organs and the placenta". Mol. Hum. Reprod. 8 (4): 385–91. doi:10.1093/molehr/8.4.385. PMID 11912287.
External links
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PDB gallery
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2d0t: Crystal structure of 4-phenylimidazole bound form of human indoleamine 2,3-dioxygenase
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2d0u: Crystal structure of cyanide bound form of human indoleamine 2,3-dioxygenase
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| 1.13.11: two atoms of oxygen |
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| 1.13.12: one atom of oxygen |
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| 1.13.99: other |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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| K→acetyl-CoA |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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