Indoleamine 2,3-dioxygenase. Purification and some properties
Open accessAbstract
Indoleamine 2,3-dioxygenase was purified from rabbit small intestine to apparent homogeneity as judged by polyacrylamide gel electrophoresis and analytical ultracentrifugation. The native enzyme was a monomeric protein of a molecular weight of 41,000 +/- 1,000 with an s020,w value of 3.45 S. It had a relative abundance of hydrophobic amino acids such as valine, leucine, and isoleucine, and contained approximately 5% carbohydrate by weight. The estimated content of sugar residues per mol of enzyme was: galactose, 1.2; mannose, 2.6; N-acetylglucosamine, 5.2; and sialic acid, 0.8. One mole of enzyme had 0.8 mol of protoheme IX as a prosthetic group. However, copper was not detected in a significant amount and the ratio of copper to heme was less than 0.03. EPR spectra of the nitric oxide complex of the ferrous enzyme indicated that a nitrogen atom, possibly in an imidazole group, might be coordinated as the fifth ligand of the heme coenzyme. The anisotropic g values were gx = 2.08, gy = 1.98, and gz = 2.01. A single enzyme protein catalyzed the oxygenative ring cleavage of D- and L-tryptophan, D- and L-5-hydroxytryptophan, tryptamine, and serotonin. In addition, the purified enzyme had a peroxidase activity with guaiacol and potassium iodide as hydrogen donors, but not a catalase activity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increased IDO expression is responsible for the catabolism of TRP in the KYN degradation pathway and is canonically upregulated by inflammatory mechanisms.
“Increased IDO expression is responsible for the catabolism of TRP in the KYN degradation pathway [36] and is canonically upregulated by inflammatory mechanisms [37,38].”
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Colorimetric Method for Determination of Sugars and Related Substances
DuBois, M., Gilles, K. A., Hamilton, J. K., Rebers, P. A., & Smith, F. (1956) · Analytical Chemistry · doi:10.1021/ac60111a017 · Cited by 52,269 · see citing works
Weber, K., & Osborn, M. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)94333-4 · Cited by 16,688 · see citing works
DISC ELECTROPHORESIS – II METHOD AND APPLICATION TO HUMAN SERUM PROTEINS *
Davis, B. J. (1964) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1964.tb14213.x · Cited by 16,129 · see citing works
McCord, J. M., & Fridovich, I. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63504-5 · Cited by 12,952 · see citing works
Automatic recording apparatus for use in the chromatography of amino acids.
Moore, S., Spackman, D., & Stein, W. (1958) · Federation proceedings · doi:10.1021/ac60139a006 · Cited by 8,126 · see citing works
The thiobarbituric acid assay of sialic acids.
Warren, L. (1959) · Journal of Biological Chemistry · doi:10.1016/0076-6879(63)06207-8 · Cited by 5,607 · see citing works
Disk Electrophoresis of Basic Proteins and Peptides on Polyacrylamide Gels
Reisfeld, R., Lewis, U., & Williams, D. E. (1962) · Nature · doi:10.1038/195281a0 · Cited by 2,569 · see citing works
Glycoprotein staining following electrophoresis on acrylamide gels.
Zacharius, R. M., Zell, T., Morrison, J., & Woodlock, J. J. (1969) · Analytical Biochemistry · doi:10.1016/0003-2697(69)90383-2 · Cited by 1,770 · see citing works
A theory of gel filtration and its exeperimental verification
Laurent, T., & Killander, J. (1964) · Journal of Chromatography A · doi:10.1016/s0021-9673(00)86637-6 · Cited by 1,352 · see citing works
The spectrophotometric determination of tyrosine and tryptophan in proteins.
Goodwin, T., & Morton, R. A. (1946) · Biochemical Journal · doi:10.1042/bj0400628 · Cited by 1,157 · see citing works
Vesterberg, O., & Svensson, H. (1966) · Acta Chemica Scandinavica · doi:10.3891/acta.chem.scand.20-0820 · Cited by 1,110 · see citing works
[2] Ultracentrifugation, diffusion, and viscometry
Schachman, H. (1957) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(57)04050-1 · Cited by 565 · see citing works
DISC ELECTROPHORESIS IN POLYACRYLAMIDE GELS: EXTENSION TO NEW CONDITIONS OF pH AND BUFFER
Williams, D. E., & Reisfeld, R. (1964) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1964.tb14210.x · Cited by 557 · see citing works
The Molar Light Absorption of Pyridine Ferroprotoporphrin (Pyridine Haemochromogen).
Paul, K., Theorell, H., Åkeson, Å., Virtanen, A. I., & Sörensen, N. A. (1953) · Acta chemica Scandinavica/Acta chemica Scandinavica. B, Organic chemistry and biochemistry/Acta chemica Scandinavica. A, Physical and inorganic chemistry/Acta chemica Scandinavica. Series B. Organic chemistry and biochemistry/Acta chemica Scandinavica. Series A, Physical and inorganic chemistry · doi:10.3891/acta.chem.scand.07-1284 · Cited by 425 · see citing works
In vitro and in vivo formation of two new metabolites of melatonin.
Hirata, F., Hayaishi, O., Tokuyama, T., & Senoh, S. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42976-1 · Cited by 302 · see citing works
Self-citationNordblom, G. D., White, R. E., & Coon, M. J. (1976) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(76)90541-5 · Cited by 296 · see citing works
Heller, J. (1968) · Biochemistry · doi:10.1021/bi00848a030 · Cited by 264 · see citing works
The Isolation and Purification of Thyroid Peroxidase
Hosoya, T., & Morrison, M. (1967) · doi:10.1016/s0021-9258(18)99581-5 · Cited by 149
Studies on indoleamine 2,3-dioxygenase. I. Superoxide anion as substrate.
Hirata, F., & Hayaishi, O. (1975) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)41144-7 · Cited by 138 · see citing works
Self-citationEnzymic formation of D-kynurenine from D-tryptophan.
Higuchi, K., & Hayaishi, O. (1967) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(67)90256-1 · Cited by 105
Self-citationIndoleamine 2,3-dioxygenase. Characterization and properties of enzyme. O2- complex.
Hirata, F., Ohnishi, T., & Hayaishi, O. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40208-0 · Cited by 94 · see citing works
Self-citationHirata, F., & Hayaishi, O. (1972) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/0006-291x(72)90949-7 · Cited by 87
Self-citationPossible participation of superoxide anion in the intestinal tryptophan 2,3-dioxygenase reaction.
Hirata, F., & Hayaishi, O. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)45852-3 · Cited by 81 · see citing works
Self-citationIndoleamine 2,3-dioxygenase: incorporation of 18O2-- and 18O2 into the reaction products.
Hayaishi, O., Hirata, F., Ohnishi, T., Henry, J. P., Rosenthal, I., & Katoh, A. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40425-x · Cited by 75
Self-citationIndoleamine 2,3-dioxygenase. Potassium superoxide as substrate.
Ohnishi, T., Hirata, F., & Hayaish, O. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40209-2 · Cited by 72
Self-citationIshimaru, A., & Yamazaki, I. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40038-x · Cited by 69 · see citing works
[4] Microdetermination of sugar composition by radioisotope labeling
Takasaki, S., & Kobata, A. (1978) · doi:10.1016/0076-6879(78)50006-2 · Cited by 69
Peterson, R. E. (1953) · doi:10.1021/ac60081a010 · Cited by 65
Intracellular utilization of superoxide anion by indoleamine 2,3-dioxygenase of rabbit enterocytes.
Taniguchi, T., Hirata, F., & Hayaishi, O. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40524-2 · Cited by 49 · see citing works
Self-citationHrycay, E., Jonen, H., Lu, A. Y. H., & Levin, W. (1975) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(75)90374-4 · Cited by 36
Studies on hog intestine mucosa peroxidase.
Stelmaszyńska, T., & Zgliczyński, J. M. (1971) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1971.tb01287.x · Cited by 30
Peterkofsky, B. (1968) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(68)90073-8 · Cited by 19
Inhibition of rabbit intestinal indoleamine 2,3‐dioxygenase by copper chelators
Brady, F. O. (1975) · FEBS Letters · doi:10.1016/0014-5793(75)80307-3 · Cited by 11
The NO-probed detection of the heme-linked ionization group of myoglobin.
Tamura, M., Kobayashi, K., & Hayashi, K.-I. (1976) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/0006-291x(76)91137-2 · Cited by 6
Flagged first, then by citations
3 of the 38 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Inhibition of T Cell Proliferation by Macrophage Tryptophan Catabolism
Munn, D., Shafizadeh, E., Attwood, J., Bondarev, I., Pashine, A., & Mellor, A. (1999) · Journal of Experimental Medicine · doi:10.1084/jem.189.9.1363 · Cited by 1,721 · see citing works
Heme Enzyme Structure and Function
Poulos, T. L. (2014) · Chemical Reviews · doi:10.1021/cr400415k · Cited by 1,443 · see citing works
Frumento, G., Rotondo, R., Tonetti, M., Damonte, G., Benatti, U., & Ferrara, G. B. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020121 · Cited by 1,133 · see citing works
T cell apoptosis by tryptophan catabolism
Fallarino, F., Grohmann, U., Vacca, C., Bianchi, R., Orabona, C., Spreca, A., Fioretti, M. C., & Puccetti, P. (2002) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401073 · Cited by 1,022 · see citing works
The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression
Müller, N., & Schwarz, M. J. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002006 · Cited by 670 · see citing works
Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity
Liu, X., Shin, N., Koblish, H. K., Yang, G., Wang, Q., Wang, K., Leffet, L., Hansbury, M., Thomas, B. A., Rupar, M. J., et al. (2010) · Blood · doi:10.1182/blood-2009-09-246124 · Cited by 549 · see citing works
Tryptophan metabolism, from nutrition to potential therapeutic applications
Floc'h, N. L., Otten, W., & Merlot, E. (2011) · Amino Acids · doi:10.1007/s00726-010-0752-7 · Cited by 529 · see citing works
“IDO is also expressed in the intestine of many species (Yamamoto and Hayaishi 1967; Yamazaki et al. 1985; Shimizu et al. 1978), where its expression and activity are high compared to other tissues even in healthy conditions (Takikawa et al.”
BackgroundTryptophan metabolism in the central nervous system: medical implications
Ruddick, J. P., Evans, A. K., Nutt, D. J., Lightman, S. L., Rook, G. A. W., & Lowry, C. A. (2006) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399406000068 · Cited by 519 · see citing works
Hardeland, R., Tan, D., & Reiter, R. J. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2009.00701.x · Cited by 474 · see citing works
Takahashi, N., Duprez, L., Grootjans, S., Cauwels, A., Nerinckx, W., DuHadaway, J. B., Goossens, V, Roelandt, R., Van Hauwermeiren, F., Libert, C., et al. (2012) · Cell Death & Disease · doi:10.1038/cddis.2012.176 · Cited by 465 · see citing works
“The substrates of IDO are indoleamines, such as tryptophan, serotonin, melatonin and tryptamine.(37) Hence, typical IDO inhibitors are indoleaminecontaining compounds, including 1-methyl-tryptophan (1-MT)(38) and MTH-Trp.”
BackgroundSugimoto, H., Oda, S.-I., Otsuki, T., Hino, T., Yoshida, T., & Shiro, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508996103 · Cited by 446 · see citing works
Kynurenines in CNS disease: regulation by inflammatory cytokines.
Campbell, B. M., Charych, E., Lee, A. W., & Möller, T. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00012 · Cited by 409 · see citing works
“REVIEW ARTICLE published: 06 February 2014 doi: 10.3389/fnins.2014.00012”
BackgroundInfluentialIndoleamine 2,3‐dioxygenase in T‐cell tolerance and tumoral immune escape
Katz, J. B., Muller, A. J., & Prendergast, G. C. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00610.x · Cited by 399 · see citing works
“Interestingly, the structure of TDO2 and IDO are dissimilar, despite catalyzing the same reaction of tryptophan to N-formylkynurenine (32).”
BackgroundLovelace, M. D., Varney, B., Sundaram, G., Lennon, M. J., Lim, C. K., Jacobs, K., Guillemin, G. J., & Brew, B. J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.03.024 · Cited by 393 · see citing works
Beyond immune checkpoint blockade: emerging immunological strategies
Kubli, S. P., Berger, T., Araújo, D. V., Siu, L. L., & Mak, T. W. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00155-y · Cited by 460 · see citing works
Biochemical and medical aspects of the indoleamine 2,3-dioxygenase-initiated l-tryptophan metabolism
Takikawa, O. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.09.032 · Cited by 340 · see citing works
Cady, S. G., & Sono, M. (1991) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(91)90142-6 · Cited by 298 · see citing works
Molecular Pathways: Targeting IDO1 and Other Tryptophan Dioxygenases for Cancer Immunotherapy
Zhai, L., Spranger, S., Binder, D. C., Gritsina, G., Lauing, K. L., Giles, F. J., & Wainwright, D. A. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0420 · Cited by 325 · see citing works
“While monomeric IDO1 acts on a broad range of substrates and is capable of cleaving both D- and L-Trp, homotetrameric TDO is enantiomerspecific andonly catabolizes L-Trp (24).”
BackgroundInfluentialReconstructing eukaryotic NAD metabolism.
Rongvaux, A., Andris, F., Gool, F. V., & Leo, O. (2003) · Bioessays · doi:10.1002/bies.10297 · Cited by 284 · see citing works
Blood-brain barrier permeability and physical exercise
Małkiewicz, M. A., Szarmach, A., Sabisz, A., Cubała, W. J., Szurowska, E., & Winklewski, P. J. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1403-x · Cited by 276 · see citing works
“It is known that both IFN-γ and TNF-α can alter BBB permeability by affecting the cellular distribution of junctional adhesion molecules and by crucial upregulating the expression of ICAM-1 and VCAM-1 [209–211].”
BackgroundInfluentialMolecular tools to study melatonin pathways and actions.
Boutin, J., Audinot, V., Ferry, G., & Delagrange, P. (2005) · TIPS - Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.06.006 · Cited by 265 · see citing works
Zhao, F. L., Xiao, C., Evans, K. S., Theivanthiran, T., DeVito, N. C., Holtzhausen, A., Liu, J., Liu, X., Boczkowski, D., Nair, S. K., et al. (2018) · Immunity · doi:10.1016/j.immuni.2017.12.004 · Cited by 286 · see citing works
“IDO requires the heme prosthetic group, protoporphyrin IX (PpIX), for full enzymatic activity (Shimizu et al., 1978).”
Immunomodulatory Properties of Mesenchymal Stem Cells: Cytokines and Factors
Soleymaninejadian, E., Pramanik, K., & Samadian, E. (2011) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2011.01069.x · Cited by 238 · see citing works
Thomas, S. R., & Stocker, R. (1999) · Redox Report · doi:10.1179/135100099101534927 · Cited by 220 · see citing works
T cell apoptosis by kynurenines.
Fallarino, F., Grohmann, U., Vacca, C., Orabona, C., Spreca, A., Fioretti, M., & Puccetti, P. (2003) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4615-0135-0_21 · Cited by 219 · see citing works
Murray, H. W., Szuro-Sudol, A., Wellner, D., Oca, M. J., Granger, A. M., Libby, D., Rothermel, C. D., & Rubin, B. Y. (1989) · Infection and Immunity · doi:10.1128/iai.57.3.845-849.1989 · Cited by 216 · see citing works
Immunosuppressive IDO in Cancer: Mechanisms of Action, Animal Models, and Targeting Strategies
Zhai, L., Bell, A., Ladomersky, E., Lauing, K. L., Bollu, L. R., Sosman, J. A., Zhang, B., Wu, J. D., Miller, S. D., Meeks, J. J., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01185 · Cited by 222 · see citing works
“TDO expression levels are regulated in-part by systemic levels of L-Trp and corticosteroids (31, 32).”
BackgroundInfluentialWu, W., Nicolazzo, J. A., Wen, L., Chung, R. S., Stankovic, R. K., Bao, S., Lim, C. K., Brew, B. J., Cullen, K. M., & Guillemin, G. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059749 · Cited by 208 · see citing works
Babcock, T., & Carlin, J. (2000) · Cytokine · doi:10.1006/cyto.1999.0661 · Cited by 193 · see citing works
Robinson, C. M., Hale, P. T., & Carlin, J. M. (2005) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2005.25.20 · Cited by 208 · see citing works
“(1,2) IDO activity represents the ratelimiting step in tryptophan catabolism along the kynurenine pathway and is an important antimicrobial defense mechanism.(3) IDO activity protects host cells from tryptophan auxotrophic pathogens by depleting pools of tryptophan required for their protein synthesis.”
IDO Expression in Cancer: Different Compartment, Different Functionality?
Meireson, A., Devos, M., & Brochez, L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.531491 · Cited by 207 · see citing works
“Indoleamine 2, 3-dioxygenase 1 (IDO1, hereafter referred to as IDO) is a 403 amino acid cytosolic haem-containing enzyme involved in the first, rate-limiting step of the tryptophan (Trp) metabolism to kynurenine (Kyn) (1, 2).”
BackgroundHill, M., Pereira, V., Chauveau, C., Zagani, R., Remy, S., Tesson, L., Mazal, D., Ubillos, L., Brion, R., Ashgar, K., et al. (2005) · The FASEB Journal · doi:10.1096/fj.05-3875com · Cited by 158 · see citing works
Fujigaki, H., Yamamoto, Y., & Saito, K. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.01.011 · Cited by 162 · see citing works
“…is the oxidative cleavage of TRP by one of the three rate-limiting enzymes, namely, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1), or indoleamine 2,3- dioxygenase 2 (IDO2), which convert TRP to N-formylkynurenine (Ball et al., 2007; Metz et al., 2007; Shimizu et al., 1978).”
Carlin, J. M., Borden, E. C., Sondel, P., & Byrne, G. I. (1987) · Journal of Immunology · doi:10.4049/jimmunol.139.7.2414 · Cited by 160 · see citing works
Interleukin-4 inhibits indoleamine 2,3-dioxygenase expression in human monocytes.
Musso, T., Gusella, G., Brooks, A., Longo, D., & Varesio, L. (1994) · Blood · doi:10.1182/blood.v83.5.1408.1408 · Cited by 158 · see citing works
Pfefferkorn, E., Rebhun, S., & Eckel, M. E. (1986) · Journal of Interferon Research · doi:10.1089/jir.1986.6.267 · Cited by 157 · see citing works
Localization of indoleamine 2,3-dioxygenase in human female reproductive organs and the placenta.
Sedlmayr, P., Blaschitz, A., Wintersteiger, R., Semlitsch, M., Hammer, A., Mackenzie, C., Walcher, W., Reich, O., Takikawa, O., & Dohr, G. (2002) · Molecular human reproduction · doi:10.1093/molehr/8.4.385 · Cited by 154 · see citing works
“IDO oxidizes the pyrrole moiety of tryptophan (Shimizu et al., 1978).”
BackgroundFatokun, A. A., Hunt, N. H., & Ball, H. J. (2013) · Amino Acids · doi:10.1007/s00726-013-1602-1 · Cited by 162 · see citing works
Rational Design of Indoleamine 2,3-Dioxygenase Inhibitors
Röhrig, U. F., Awad, L., Grosdidier, A., Larrieu, P., Stroobant, V., Colau, D., Cerundolo, V., Simpson, A. J. G., Vogel, P., den Eynde, B. J. V., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm9014718 · Cited by 162 · see citing works
Tryptophan-Catabolizing Enzymes – Party of Three
Ball, H. J., Jusof, F. F., Bakmiwewa, S. M., Hunt, N. H., & Yuasa, H. J. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00485 · Cited by 181 · see citing works
“IDO1 was originally isolated from rabbit intestine as a d-Trp-catabolizing enzyme (16) and its substrates include d- and l-Trp, tryptamine, 5-hydroxytryptophan, and 5-hydroxytryptamine (17).”
BackgroundIndoleamine 2,3-Dioxygenase in Immune Suppression and Cancer
Muller, A. J., & Prendergast, G. C. (2007) · Current Cancer Drug Targets · doi:10.2174/156800907780006896 · Cited by 146 · see citing works
Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early concepti.
Suzuki, S., Toné, S., Takikawa, O., Kubo, T., Kohno, I., & Minatogawa, Y. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3550425 · Cited by 148 · see citing works
Interferon‐lnduced Indoleamine 2,3‐Dioxygenase Activity in Human Mononuclear Phagocytes
Carlin, J. M., Borden, E. C., Sondel, P., & Byrne, G. I. (1989) · Journal of Leukocyte Biology · doi:10.1002/jlb.45.1.29 · Cited by 144 · see citing works
Lewis-Ballester, A., Pham, K., Batabyal, D., Karkashon, S., Bonanno, J. B., Poulos, T. L., & Yeh, S. (2017) · Nature Communications · doi:10.1038/s41467-017-01725-8 · Cited by 171 · see citing works
Jones, S. P., Franco, N. F., Varney, B., Sundaram, G., Brown, D. A., de Bie, J., Lim, C. K., Guillemin, G. J., & Brew, B. J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131389 · Cited by 142 · see citing works
“The most potent activator of IDO-1 is interferon gamma (IFN-γ) [3, 12].”
BackgroundRobinson, C. M., Shirey, K., & Carlin, J. (2003) · Journal of Interferon & Cytokine Research · doi:10.1089/107999003322277829 · Cited by 140 · see citing works
“(4) This activity depletes intracellular and extracellular pools of the essential amino acid, thereby re-stricting growth of susceptible pathogens, such as Chlamydia spp. (2,5,6) and Toxoplasma gondii (7,8) in vitro .”
Melatonin Metabolism in the Central Nervous System
Hardeland, R. (2010) · Current Neuropharmacology · doi:10.2174/157015910792246244 · Cited by 134 · see citing works
“However, the major fraction of c3OHM was reported to be present as a sulfate conjugate [80].”
BackgroundEvolution of Vertebrate Indoleamine 2,3-Dioxygenases
Yuasa, H., Takubo, M., Takahashi, A., Hasegawa, T., Noma, H., & Suzuki, T. (2007) · Journal of Molecular Evolution · doi:10.1007/s00239-007-9049-1 · Cited by 134
“While TDO is highly specific for L-Trp, IDO has a much broader substrate specificity, with substrates including L-Trp, D-Trp, 5-hydroxy-Trp, tryptamine, and serotonin (Shimizu et al. 1978; Takikawa 2005).”
Corona, A. W., Norden, D. M., Skendelas, J. P., Huang, Y., O’Connor, J. C., Lawson, M. A., Dantzer, R., Kelley, K. W., & Godbout, J. P. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.08.008 · Cited by 150 · see citing works
“In addition, IDO also degrades 5′hydroxytryptophan (5- HTP) and 5-HT to 5-hydroxykynuramine (Fujiwara et al., 1979; Shimizu et al., 1978) (Fig.”
BackgroundCDllc+ cells modulate pulmonary immune responses by production of indoleamine 2,3-dioxygenase.
Swanson, K., Zheng, Y., Heidler, K., Mizobuchi, T., & Wilkes, D. (2004) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2003-0268oc · Cited by 129 · see citing works
Ziklo, N., Vidgen, M. E., Taing, K., Huston, W. M., & Timms, P. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00001 · Cited by 234 · see citing works
Däubener, W., & MacKenzie, C. R. (1999) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-4709-9_64 · Cited by 120 · see citing works
Dai, X., & Zhu, B. T. (2009) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.2009.953604 · Cited by 128 · see citing works
“13.11.42), the rate-limiting enzyme of the kynurenine pathway, catalyzes the oxidative conversion of L-tryptophan to N-formylkynurenine (Hirata and Haysishi 1975; Shimizu et al. 1978).”
BackgroundInfluentialStudy of the brain serotonergic system with labeled α‐methyl‐ l ‐tryptophan
Dikšić, M., & Young, S. N. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00536.x · Cited by 111 · see citing works
“The substrate speci®city of indoleamine-2,3-dioxygenase is low (Shimizu et al. 1978), and it will catabolize a-MTrp.”
BackgroundCriado, G., Šimelyte, E., Inglis, J. J., Essex, D. W., & Williams, R. O. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24446 · Cited by 127 · see citing works
The Immunoregulatory Enzyme IDO Paradoxically Drives B Cell-Mediated Autoimmunity
Scott, G. N., DuHadaway, J., Pigott, E., Ridge, N., Prendergast, G., Muller, A., & Mandik-Nayak, L. (2009) · Journal of Immunology · doi:10.4049/jimmunol.0804328 · Cited by 114 · see citing works
Ligam, P., Manuelpillai, U., Wallace, E., & Walker, D. (2005) · Placenta · doi:10.1016/j.placenta.2004.08.009 · Cited by 112 · see citing works
Muller, A. J., Malachowski, W. P., & Prendergast, G. C. (2005) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.9.4.831 · Cited by 114 · see citing works
Amino Acid Transport Regulation and Early Embryo Development
Winkle, L. J. V. (2001) · Biology of Reproduction · doi:10.1095/biolreprod64.1.1 · Cited by 181 · see citing works
“Moreover, the Km values for leucine, tryptophan, and arginine transport via systems B0,1 and b0,1 are in the low micromolar range [23, 42, 58], and they are lower than the Km value of IDO for tryptophan [95, 98].”
BackgroundZhai, L., Bell, A., Ladomersky, E., Lauing, K. L., Bollu, L., Nguyen, B., Genet, M., Kim, M., Chen, P., Mi, X., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1392 · Cited by 129 · see citing works
“IDO is canonically characterized as a rate-limiting immunosuppressive enzyme that converts the essential amino acid, tryptophan (Trp), into downstream metabolites that are collectively referred to as kynurenines (Kyn) (9).”
BackgroundSinglet molecular oxygen regulates vascular tone and blood pressure in inflammation
Stanley, C. P., Maghzal, G., Ayer, A., Talib, J., Giltrap, A. M., Shengule, S., Wolhuter, K., Wang, Y.-T., Chadha, P., Suarna, C., et al. (2019) · Nature · doi:10.1038/s41586-019-0947-3 · Cited by 103 · see citing works
Antimicrobial and immunoregulatory properties of human tryptophan 2,3‐dioxygenase
Schmidt, S., Müller, A., Heseler, K., Woite, C., Spekker, K., Mackenzie, C., & Däubener, W. (2009) · European Journal of Immunology · doi:10.1002/eji.200939535 · Cited by 97 · see citing works
Ferry, G., Ubeaud, C., Lambert, P., Bertin, S., Cogé, F., Chomarat, P., Delagrange, P., Serkiz, B., Bouchet, J., Truscott, R., et al. (2005) · Biochemical Journal · doi:10.1042/bj20042075 · Cited by 95 · see citing works
Currier, A. R., Ziegler, M., Riley, M., Babcock, T., Telbis, V. P., & Carlin, J. (2000) · Journal of Interferon and Cytokine Research · doi:10.1089/107999000312306 · Cited by 92 · see citing works
Metabolomics and Metabolic Reprogramming in Kidney Cancer
Weiss, R. H. (2018) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2018.01.006 · Cited by 108 · see citing works
Agaugué, S., Perrin‐Cocon, L., Coutant, F., André, P., & Lotteau, V. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.4.2061 · Cited by 86 · see citing works
Shima, N., Stolz, D. B., Miyazaki, M., Gohda, E., Higashio, K., & Michalopoulos, G. K. (1998) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199810)177:1 · Cited by 26 · see citing works
Interferons and indoleamine 2,3-dioxygenase: Role in antimicrobial and antitumor effects
Carlin, J. M., Ozaki, Y., Byrne, G. I., Brown, R. R., & Borden, E. C. (1989) · Experientia · doi:10.1007/bf01990503 · Cited by 87 · see citing works
Beta interferon inhibits Toxoplasma gondii growth in human monocyte-derived macrophages
Schmitz, J., Carlin, J. M., Borden, E. C., & Byrne, G. I. (1989) · Infection and Immunity · doi:10.1128/iai.57.10.3254-3256.1989 · Cited by 86 · see citing works
“IDO has been shown to mediate the inhibition by catalyzing the decyclization of tryptophan to N-formylkynurenine (12), thus depriving the infecting organism of the essential amino acid tryptophan (9).”
BackgroundLee, S., Lee, Y.-S., Choi, J.-H., Park, S.-G., Choi, I., Joo, Y., Lee, W.-S., Lee, J.-N., Choi, I., & Seo, S. (2010) · Immunology Letters · doi:10.1016/j.imlet.2010.05.008 · Cited by 78 · see citing works
“Indoleamine 2,3-dioxygenase (IDO) is a cytoplasmic enzyme hat converts tryptophan to catabolic products, collectively known s kynurenines [1,2].”
BackgroundChung, L. W., Li, X., Sugimoto, H., Shiro, Y., & Morokuma, K. (2010) · Journal of the American Chemical Society · doi:10.1021/ja103530v · Cited by 100 · see citing works
Indoleamine 2,3-Dioxygenase, an Emerging Target for Anti-Cancer Therapy
Liu, X., Newton, R., Friedman, S., & Scherle, P. (2009) · Current Cancer Drug Targets · doi:10.2174/156800909790192374 · Cited by 83 · see citing works
Rafice, S. A., Chauhan, N., Efimov, I., Basran, J., & Raven, E. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370408 · Cited by 83 · see citing works
In Vivo Uptake and Metabolism of α-[11C]Methyl- l -Tryptophan in Human Brain Tumors
Juhász, C., Chugani, D. C., Muzik, O., Wu, D., Sloan, A. E., Barger, G. R., Watson, C. E., Shah, A. K., Sood, S., Ergün, E. L., et al. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600199 · Cited by 90 · see citing works
Identification of Tryptophan 2,3‐Dioxygenase RNA in Rodent Brain
Haber, R., Bessette, D., Hulihan-Giblin, B., Durcan, M., & Goldman, D. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03269.x · Cited by 83
Immunological Relevance of the Coevolution of IDO1 and AHR
Jaronen, M., & Quintana, F. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00521 · Cited by 80 · see citing works
“Indoleamine-2,3-dioxygenase (IDO1), tryptophan2,3-dioxygenase (TDO), and recently discovered IDO-related enzyme IDO2 (54) are the first and rate-limiting enzymes converting tryptophan to N -formylkynurenine (55, 56) which is then metabolized to l-kynurenine.”
BackgroundPossible roles of excess tryptophan metabolites in cancer
Chung, K., & Gadupudi, G. (2011) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20588 · Cited by 79 · see citing works
“Although both TDO and IDO catalyze the same reaction [Shimizu et al., 1978; Yamazaki et al., 1985], TDO is highly substrate-specific, only dioxygenating L-tryptophan and some tryptophan derivatives substituted in the five- and six-positions.”
BackgroundPapadopoulou, N. D., Mewies, M., McLean, K., Seward, H. E., Svistunenko, D., Munro, A., & Raven, E. (2005) · Biochemistry · doi:10.1021/bi0513958 · Cited by 78
Sono, M., & Cady, S. G. (1989) · Biochemistry · doi:10.1021/bi00439a012 · Cited by 78
Jovanović, F., Candido, K. D., & Knežević, N. N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176045 · Cited by 79 · see citing works
Hu, B.-G., Hissong, B., & Carlin, J. (1995) · Journal of Interferon and Cytokine Research · doi:10.1089/jir.1995.15.617 · Cited by 76 · see citing works
El-zaatari, M., Chang, Y.-M., Zhang, M. F., Franz, M., Shreiner, A., McDermott, A. J., van der Sluijs, K. F., Lutter, R., Grasberger, H., Kamada, N., et al. (2014) · Journal of Immunology · doi:10.4049/jimmunol.1302913 · Cited by 75 · see citing works
Shirey, K., Jung, J., Maeder, G., & Carlin, J. (2006) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2006.26.53 · Cited by 75 · see citing works
“IDO catalyzes the decyclization of L -tryptophan into N -formylkynurenine, 5 thereby limiting the availability of this essential amino acid and, consequently, inhibiting the growth of tryptophan auxotrophs.”
A Perspective on the Safety of Supplemental Tryptophan Based on Its Metabolic Fates.
Fernstrom, J. (2016) · Journal of NutriLife · doi:10.3945/jn.115.228643 · Cited by 74 · see citing works
A high-affinity, tryptophan-selective amino acid transport system in human macrophages
Seymour, R. L., Ganapathy, V., Mellor, A. L., & Munn, D. H. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.1205727 · Cited by 66 · see citing works
Eguchi, N., Watanabe, Y., Kawanishi, K., Hashimoto, Y., & Hayaishi, O. (1984) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(84)90579-4 · Cited by 73 · see citing works
Self-citationRobinson, C. M., Hale, P. T., & Carlin, J. M. (2006) · Cytokine · doi:10.1016/j.cyto.2006.07.007 · Cited by 65 · see citing works
Dang, Y.-H., Dale, W. E., & Brown, O. R. (2000) · Free Radical Biology & Medicine · doi:10.1016/s0891-5849(99)00272-5 · Cited by 72 · see citing works
WANG, D., Saga, Y., Mizukami, H., Sato, N., NONAKA, H., Fujiwara, H., Takei, Y., 町田, 静., Takikawa, O., Ozawa, K., et al. (2011) · International Journal of Oncology · doi:10.3892/ijo.2011.1295 · Cited by 73 · see citing works
“IDO was originally discovered in 1967 (7,8) in the rabbit small intestine and was first purified in 1978 (9).”
BackgroundBiochemical characteristics and inhibitor selectivity of mouse indoleamine 2,3-dioxygenase-2
Austin, C. J. D., Mailu, B. M., Maghzal, G., Sánchez-Pérez, Á., Rahlfs, S., Zocher, K., Yuasa, H., Arthur, J. W., Becker, K., Stocker, R., et al. (2010) · Amino Acids · doi:10.1007/s00726-010-0475-9 · Cited by 71 · see citing works
Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies
Juhász, C., Nahleh, Z. A., Zitron, I. M., Chugani, D. C., Janabi, M., Bandyopadhyay, S., Ali‐Fehmi, R., Mangner, T. J., Chakraborty, P. K., Mittal, S., et al. (2012) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2012.01.010 · Cited by 78 · see citing works
“However, it is a substrate for TPH (leading to synthesis of alpha-methyl-serotonin) [19,20] and IDO (due to its low substrate specificity) [21,22].”
BackgroundResearch Progress of Indoleamine 2,3-Dioxygenase Inhibitors
Jiang, T., Sun, Y., Yin, Z., Feng, S., Sun, L., & Li, Z. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.14.151 · Cited by 73 · see citing works
Littlejohn, T., Takikawa, O., Truscott, R., & Walker, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301700200 · Cited by 69
Analysis of Transcription Factors Regulating Induction of Indoleamine 2,3-Dioxygenase by IFN- gamma
Du, M. X., Sotero-Esteva, W. D., & Taylor, M. W. (2000) · Journal of Interferon & Cytokine Research · doi:10.1089/107999000312531 · Cited by 66 · see citing works
“(25,38) Substantial increases in the tryptophan-kynurenine pathway metabolites, 1-kynurenine and the neuro-toxin quinolinic acid, occur in human brain, blood, and systemic tissues during immune activation.”
Lood, C., Tydén, H., Gullstrand, B., Klint, C., Wenglén, C., Nielsen, C., Heegaard, N., Jönsen, A., Kahn, R., & Bengtsson, A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125109 · Cited by 67 · see citing works
“Interestingly, even though IDO mainly catalyzes the conversion of tryptophan into kynurenine, several other IDO substrates have been described, including serotonin itself [44].”
BackgroundThe Kynurenine Pathway in Stem Cell Biology
Jones, S., Guillemin, G., & Brew, B. (2013) · International Journal of Tryptophan Research · doi:10.4137/ijtr.s12626 · Cited by 66 · see citing works
Characterization and evolution of vertebrate indoleamine 2, 3-dioxygenases
Yuasa, H. J., Ball, H. J., Ho, Y. F., Austin, C., Whittington, C. M., Belov, K., Maghzal, G. J., Jermiin, L. S., & Hunt, N. H. (2009) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2009.02.002 · Cited by 72 · see citing works
Terakata, M., Fukuwatari, T., Kadota, E., Sano, M., Kanai, M., Nakamura, T., Funakoshi, H., & Shibata, K. (2013) · Journal of NutriLife · doi:10.3945/jn.113.176875 · Cited by 65 · see citing works
The Mechanism of Substrate Inhibition in Human Indoleamine 2,3-Dioxygenase
Efimov, I., Basran, J., Sun, X., Chauhan, N., Chapman, S., Mowat, C., & Raven, E. (2012) · Journal of the American Chemical Society · doi:10.1021/ja208694g · Cited by 65 · see citing works
Indoleamine and tryptophan 2,3-dioxygenases as important future therapeutic targets
Dolšak, A., Gobec, S., & Sova, M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107746 · Cited by 73 · see citing works
- Authors
- Shimizu, T., Nomiyama, S., Hirata, F., & Hayaishi, O.
- Affiliations
- Kyoto University (JP)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1978-07
- Volume
- 253
- Issue
- 13
- Pages
- 4700-4706
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1607682771
- Cited by
- 367
- References
- 38
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 14 · 2020: 9 · 2019: 10 · 2018: 9 · 2017: 13 · 2016: 15 · 2015: 12 · 2014: 13 · 2013: 12 · 2012: 20
- FWCI
- 5.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- indoleamine 2,3-dioxygenase, enzyme purification, rabbit small intestine, protoheme, sialic acid, carbohydrate content, protein secondary structure, electron spin resonance, tryptophan oxidation, serotonin oxidation, peroxidase activity, guaiacol
- MeSH terms
- Amino Acids, Animals, Electrophoresis, Disc, Hexoses, Hydrogen-Ion Concentration, Indoles, Intestine, Small, Molecular Weight, Oxygenases, Rabbits, Seasons, Substrate Specificity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
