Quinolinate as a Marker for Kynurenine Metabolite Formation and the Unresolved Question of NAD(+) Synthesis During Inflammation and Infection
Open accessAbstract
Quinolinate (Quin) is a classic example of a biochemical double-edged sword, acting as both essential metabolite and potent neurotoxin. Quin is an important metabolite in the kynurenine pathway of tryptophan catabolism leading to the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). As a precursor for NAD+, Quin can direct a portion of tryptophan catabolism toward replenishing cellular NAD+ levels in response to inflammation and infection. Intracellular Quin levels increase dramatically in response to immune stimulation (e.g., lipopolysaccharide; LPS or pokeweed mitogen; PWM) in macrophages, microglia, dendritic cells and other cells of the immune system. NAD+ serves numerous functions including energy production, the poly ADP ribose polymerization (PARP) reaction involved in DNA repair and the activity of various enzymes such as the NAD+-dependent deacetylases known as sirtuins. We used highly specific antibodies to protein-coupled Quin to delineate cells that accumulate Quin as a key aspect of the response to immune stimulation and infection. Here we describe Quin staining in the brain, spleen and liver after LPS administration to the brain or systemic PWM administration. Quin expression was strong in immune cells in the periphery after both treatments, whereas very limited Quin expression was observed in the brain even after direct LPS injection. Immunoreactive cells exhibited diverse morphology ranging from foam-cells to cells with membrane extensions related to cell motility. We also examined protein expression changes in the spleen after kynurenine administration. Acute (8 hr) and chronic (48 hr) kynurenine administration led to significant changes in protein expression in the spleen, including multiple changes involved with cytoskeletal rearrangements associated with cell motility and phagocytosis. Kynurenine administration resulted in several expression level changes in proteins associated with heat shock protein 90 (HSP90), a chaperone for the aryl-hydrocarbon receptor (AHR), which is the primary kynurenine metabolite receptor. We propose that cells with high levels of Quin are those that are currently releasing kynurenine pathway metabolites as well as accumulating Quin for sustained NAD+ synthesis from tryptophan. Further, the kynurenine pathway may be linked to the regulation of cell motility in immune and cancer cells.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Elevated QUIN levels in leukocytes during inflammatory responses contribute to increased NAD+.
“Several studies indicate elevated QUIN levels in leukocytes, during inflammatory responses, contribute to increased NAD+ [61,62].”
From VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice (2024) · cites this paper as [61]
The Discussion section on Quin accumulation reports elevated intracellular Quin in immune cells and says it could support sustained conversion to NAD+, but presents that role as a possibility rather than an established effect. The section on NAD+ synthesis outside the liver also reports that IFN-γ treatment alone decreased NAD+ levels in human monocytes and macrophages; increases were observed when PARP was inhibited. Page numbers are not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor
Opitz, C. A., Litzenburger, U. M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., et al. (2011) · Nature · doi:10.1038/nature10491 · Cited by 1,898 · see citing works
Schopf, F. H., Biebl, M. M., & Buchner, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.20 · Cited by 1,540 · see citing works
Kynurenines in the mammalian brain: when physiology meets pathology
Schwarcz, R., Bruno, J. P., Muchowski, P. J., & Wu, H.-Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3257 · Cited by 1,530 · cited 1× · see citing works
“Yet, the precise nature of the benefits that the kynurenine pathway confers on fitness is a matter of ongoing debate (7, 9, 16, 22, 23).”
BackgroundActin Dynamics, Architecture, and Mechanics in Cell Motility
Blanchoin, L., Boujemaa‐Paterski, R., Sykes, C., & Plastino, J. (2014) · Physiological Reviews · doi:10.1152/physrev.00018.2013 · Cited by 1,468 · cited 1× · see citing works
“Motile macrophages employ the cortical cytoskeleton to generate membrane protrusions that facilitate cell migration through tissues [reviewed in (74)].”
BackgroundKynurenine pathway of tryptophan metabolism: regulatory and functional aspects
Badawy, A. A.-B. (2017) · International Journal of Tryptophan Research · doi:10.1177/1178646917691938 · Cited by 1,158 · cited 2× · see citing works
“One noteworthy feature of kynurenine loading is production of kynurenic acid, as the relevant kynurenine aminotransferase reaction (see Figure 1) is dependent on the high substrate concentrations due to the high Km of the enzyme for kynurenine (46).”
BackgroundSelf-citationKunjathoor, V., Febbraio, M., Podrez, E., Moore, K., Andersson, L., Koehn, S. L., Rhee, J. S., Silverstein, R., Hoff, H., & Freeman, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209649200 · Cited by 1,064 · cited 1× · see citing works
“Foam cells are lipidladen macrophages that have taken up oxidized lipids, and this form of macrophage has been associated with disorders including atherosclerosis (69, 70).”
BackgroundIDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance
Munn, D. H., & Mellor, A. L. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.01.002 · Cited by 1,054 · cited 1× · see citing works
“More recently, attention has also turned to the immunomodulatory and immunosuppressive effects of kynurenine metabolites (10, 11).”
BackgroundT 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 · cited 1× · see citing works
“Selective induction of apoptosis is a frequently cited action of some kynurenine metabolites (75).”
BackgroundAlban, A., David, S., Bjorkesten, L., Andersson, C., Sloge, E., Lewis, S., & Currie, I. (2003) · Proteomics · doi:10.1002/pmic.200390006 · Cited by 919 · cited 1× · see citing works
“2D Gel Analysis The quantitative fluorescent 2D-DIGE proteomic methods have been described previously (33) and involve labeling protein samples from control and experimental groups with distinct fluorescent dyes prior to 2D gel analysis (49).”
MethodCamacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.006 · Cited by 901 · cited 4× · see citing works
“Certain host enzymes/receptors also have NAD+ hydrolase activity including CD38 and CD157, which are ADP-ribosyl cyclases and hydrolases.”
BackgroundInfluentialThe movers and shapers in immune privilege of the CNS
Engelhardt, B., Vajkoczy, P., & Weller, R. O. (2017) · Nature Immunology · doi:10.1038/ni.3666 · Cited by 893 · cited 1× · see citing works
“The brain is an immune-privileged organ, with heightened barriers to peripheral immune cell trafficking, and therefore, it does not respond to immune challenges to the same degree as many peripheral organ systems [reviewed in (66)].”
BackgroundThe kynurenine pathway: a finger in every pie
Savitz, J. B. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0414-4 · Cited by 774 · see citing works
Tryptophan and the immune response
Moffett, J., & Namboodiri, M. (2003) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.2003.t01-1-01177.x · Cited by 765 · cited 2× · see citing works
“Yet, the precise nature of the benefits that the kynurenine pathway confers on fitness is a matter of ongoing debate (7, 9, 16, 22, 23).”
BackgroundSelf-citationThe development of the DIGE system: 2D fluorescence difference gel analysis technology
Marouga, R., David, S., & Hawkins, E. (2005) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-005-3126-3 · Cited by 641 · cited 1× · see citing works
“All three labeled protein samples from each pair of animals were mixed, and each mixture was subjected to 2-D gel electrophoresis (34).”
MethodDixon, L. J., Barnes, M. A., Tang, H., Pritchard, M., & Nagy, L. E. (2013) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2013.tb00510.x · Cited by 633 · cited 1× · see citing works
“For example, in Kupffer cells (hepatic macrophages), LPS activates TRL4 receptors, whereas PWM activates the complement system via cleavage of C3 (32).”
BackgroundDiNatale, B. C., Murray, I. A., Schroeder, J. C., Flaveny, C. A., Lahoti, T. S., Laurenzana, E. M., Omiecinski, C. J., & Perdew, G. H. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq024 · Cited by 631 · see citing works
Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation
Minhas, P. S., Liu, L., Moon, P. K., Joshi, A. U., Dove, C., Mhatre, S., Contrepois, K., Wang, Q., Lee, B. A., Coronado, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0255-3 · Cited by 501 · see citing works
II: Excitotoxic models for neurodegenerative disorders
Schwarcz, R., Foster, A., French, E., Whetsell, W., & Köhler, C. (1984) · Life Sciences · doi:10.1016/0024-3205(84)90148-6 · Cited by 442 · 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 · cited 1× · see citing works
“production of kynurenine, which is released for uptake by cells of the immune system thus diverting tryptophan metabolism to the immune system, (2) the production of NAD in cells of the immune system for the PARP reaction to DNA damage and other critical functions in immune cells, and (3) the production and release of”
BackgroundMcLaren, J. E., Michael, D. R., Ashlin, T. G., & Ramji, D. P. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2011.04.002 · Cited by 395 · cited 1× · see citing works
“Some of the Quin-IR cells in the choroid plexus appeared to be foam cells, which are macrophages that are filled with lipid-laden vesicles [reviewed in (38)].”
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
The Aryl Hydrocarbon Receptor: Connecting Immunity to the Microenvironment
Shinde, R. S., & McGaha, T. L. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.10.010 · Cited by 331 · cited 1× · see citing works
“AHR is then transported to the nucleus where it forms a transcription factor complex and binds to specific DNA response elements [reviewed in (83)].”
BackgroundAndersson, P.-B., Perry, V. H., & Gordon†, S. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90347-5 · Cited by 324 · cited 1× · see citing works
“LPS is known to disrupt the blood–brain barrier (41) and injections into the hippocampus elicit strong immune cell infiltration and microglial activation over the course of 7 or more days (42).”
BackgroundLiver Macrophages: Old Dogmas and New Insights
Guillot, A., & Tacke, F. (2019) · Hepatology Communications · doi:10.1002/hep4.1356 · Cited by 309 · see citing works
Induction of pulmonary indoleamine 2,3-dioxygenase by interferon.
Yoshida, R., Imanishi, J., Oku, T., Kishida, T., & Hayaishi, O. (1981) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.78.1.129 · Cited by 288 · cited 1× · see citing works
“An important activator of TDO is cortisol, whereas interferon-γ is one of the more potent inducers of IDO activity (90, 91).”
BackgroundGharbi, S., Gaffney, P., Yang, A., Zvelebil, M., Cramer, R., Waterfield, M., & Timms, J. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.t100007-mcp200 · Cited by 287 · see citing works
ERM proteins regulate cytoskeleton relaxation promoting T cell–APC conjugation
Faure, S., Salazar-Fontana, L., Sémichon, M., Tybulewicz, V., Bismuth, G., Trautmann, A., Germain, R., & Delon, J. (2004) · Nature Immunology · doi:10.1038/ni1039 · Cited by 286 · cited 1× · see citing works
“ERM proteins are critically involved in the formation of the immunological synapse between T cells and antigenpresenting cells (77), and their phosphorylation is associated with the exclusion of certain surface proteins from the contact zone between the two cell types.”
BackgroundThe Plasma [Kynurenine]/[Tryptophan] Ratio and Indoleamine 2,3-Dioxygenase: Time for Appraisal
Badawy, A. A. ‐., & Guillemin, G. J. (2019) · International Journal of Tryptophan Research · doi:10.1177/1178646919868978 · Cited by 221 · cited 2× · see citing works
“Because both serum tryptophan and kynurenine are substantially albumin-bound (65), the observed changes in serum albumin levels would be expected to alter the free/bound tryptophan and kynurenine ratios, and downstream flux through the kynurenine pathway.”
BackgroundMethodSelf-citationEffects of immune activation on quinolinic acid and neuroactive kynurenines in the mouse.
Saito, K., Markey, S., & Heyes, M. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90467-g · Cited by 196 · cited 1× · see citing works
“During potent immune stimulation, Quin levels rise in many tissues, but brain levels remain low (92, 103).”
BackgroundRecent advances in p97/VCP/Cdc48 cellular functions.
Yamanaka, K., Sasagawa, Y., & Ogura, T. (2012) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamcr.2011.07.001 · Cited by 195 · cited 1× · see citing works
“VCP is involved in several processes including protein quality control (ERAD), autophagy, and autophagosome–lysosome fusion, among others (53).”
BackgroundSingle cell analysis of kynurenine and System L amino acid transport in T cells
Sinclair, L. V., Neyens, D., Ramsay, G., Taylor, P. M., & Cantrell, D. A. (2018) · Nature Communications · doi:10.1038/s41467-018-04366-7 · Cited by 195 · cited 1× · see citing works
“SLC7A5 is also involved in kynurenine uptake and is expressed in T cells (95), B cells (96), and monocytes/macrophages (97), indicating that all of these cell types are able to take up extracellular kynurenine.”
BackgroundA mechanism for increased quinolinic acid formation following acute systemic immune stimulation.
Saito, K., Crowley, J. S., Markey, S., & Heyes, M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82284-0 · Cited by 194 · cited 4× · see citing works
“the spleen (92), which is consistent with our current findings.”
BackgroundMethodResultInfluentialHigh‐throughput proteomic analysis of human infiltrating ductal carcinoma of the breast
Somiari, R. I., Sullivan, A. G., Russell, S., Somiari, S., Hu, H., Jordan, R. M., George, A., Katenhusen, R. A., Buchowiecka, A. K., Arciero, C. A., et al. (2003) · PROTEOMICS · doi:10.1002/pmic.200300560 · Cited by 185 · see citing works
Indoleamine 2,3‐dioxygenase: From catalyst to signaling function
Fallarino, F., Grohmann, U., & Puccetti, P. (2012) · European Journal of Immunology · doi:10.1002/eji.201242572 · Cited by 185 · cited 1× · see citing works
“More recently, attention has also turned to the immunomodulatory and immunosuppressive effects of kynurenine metabolites (10, 11).”
BackgroundTryptophan Metabolites and Brain Disorders
Stone, T. W., Mackay, G. M., Forrest, C., Clark, C. J., & Darlington, L. (2003) · Clinical Chemistry and Laboratory Medicine · doi:10.1515/cclm.2003.129 · Cited by 181 · 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
Routy, J., Routy, B., Graziani, G. M., & Mehraj, V. (2016) · International Journal of Tryptophan Research · doi:10.4137/ijtr.s38355 · Cited by 171 · cited 1× · see citing works
“Even though kynurenine pathway activity in the brain is lower than in the periphery, the kynurenine pathway has been shown to be critical for immune privilege in the brain (67).”
BackgroundPajuelo, D., González-Juarbe, N., Tak, U., Sun, J., Orihuela, C., & Niederweis, M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.042 · Cited by 170 · see citing works
Novikov, O., Wang, Z., Stanford, E. A., Parks, A. J., Ramirez-Cardenas, A., Landesman, E., Laklouk, I., Sarita-Reyes, C., Gusenleitner, D., Li, A., et al. (2016) · Molecular Pharmacology · doi:10.1124/mol.116.105361 · Cited by 167 · see citing works
NAD<sup>+</sup>metabolism and oxidative stress: the golden nucleotide on a crown of thorns
Massudi, H., Grant, R., Guillemin, G. J., & Braidy, N. (2012) · Redox Report · doi:10.1179/1351000212y.0000000001 · Cited by 158 · cited 1× · see citing works
“To this day, the extent and criticality of the contribution of tryptophan catabolism to NAD synthesis in cells of the immune system during health and disease remain mostly unexplored (12).”
BackgroundTrace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR)
Seok, S.-H., Ma, Z.-X., Feltenberger, J. B., Chen, H., Chen, H., Scarlett, C., Lin, Z., Satyshur, K. A., Cortopassi, M., Jefcoate, C. R., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000631 · Cited by 157 · see citing works
Diry, M., Tomkiewicz, C., Koehle, C., Coumoul, X., Bock, K., Barouki, R., & Transy, C. (2006) · Oncogene · doi:10.1038/sj.onc.1209553 · Cited by 157 · cited 1× · see citing works
“Activation of the AHR in epithelial cells led to morphological changes associated with cytoskeletal remodeling, increased interaction with the extracellular matrix, and reduced cell–cell contacts (87).”
BackgroundFuertig, R., Ceci, A., Camus, S., Bézard, E., Luippold, A. H., & Hengerer, B. (2016) · Bioanalysis · doi:10.4155/bio-2016-0111 · Cited by 156 · see citing works
L-Tryptophan: Biochemical, nutritional and pharmacological aspects
Sainio, E., Pulkki, K., & Young, S. (1996) · Amino Acids · doi:10.1007/bf00806091 · Cited by 155 · cited 1× · see citing works
“Humans require ∼250mg of tryptophan per day to maintain nitrogen balance, but modern diets rich in dairy products and meat contain 3–4 times as much or more (119).”
BackgroundWang, Z.-Y., Qiu, H., He, J.-B., Liu, L.-X., Xue, W., Fox, A. H., Tickner, J. C., & Xu, J.-K. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29186 · Cited by 143 · cited 1× · see citing works
“hnRNPK is a DNA-binding protein that can act as a transcription enhancer or repressor (56).”
BackgroundRole of SLC7A5 in Metabolic Reprogramming of Human Monocyte/Macrophage Immune Responses
Yoon, B. R., Oh, Y.-J., Kang, S. W., Lee, E. B., & Lee, W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00053 · Cited by 143 · cited 1× · see citing works
“SLC7A5 is also involved in kynurenine uptake and is expressed in T cells (95), B cells (96), and monocytes/macrophages (97), indicating that all of these cell types are able to take up extracellular kynurenine.”
BackgroundJones, 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 · cited 4× · see citing works
“IDO, KMO and QPRT (see Figure 1) are all upregulated in human peripheral blood monocytes by IFN-γ (113), and this is consistent with the potential for extra hepatic NAD+ synthesis in macrophages.”
BackgroundInfluentialChen, J.-Y., Li, C., Kuo, C.-C., Tsai, K. K., Hou, M., & Hung, W.-C. (2014) · Breast Cancer Research · doi:10.1186/s13058-014-0410-1 · Cited by 137 · cited 1× · see citing works
“This suggests that cells such as fibroblasts that release kynurenine (45) may feed Quin synthesis and NAD production in other cell types.”
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
Moffett, J. R., Namboodiri, M., & Neale, J. (1993) · Journal of Histochemistry and Cytochemistry · doi:10.1177/41.4.8450195 · Cited by 125 · cited 3× · see citing works
“Animal Perfusions The animals were anesthetized with pentobarbital and perfused transcardially with 400ml of an aqueous solution of 6% 1-ethyl3 (3-dimethylaminopropyl) carbodiimide hydrochloride, 6% DMSO, and 1mM N-hydroxysuccinimide warmed to 37C (26, 30).”
MethodSelf-citationNanosensor Detection of an Immunoregulatory Tryptophan Influx/Kynurenine Efflux Cycle
Kaper, T., Looger, L. L., Takanaga, H., Platten, M., Steinman, L., & Frommer, W. B. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050257 · Cited by 121 · cited 1× · see citing works
“Interestingly, extracellular tryptophan can be exchanged with intracellular kynurenine across the plasma membrane in cells in culture via the large neutral amino acid transporter SLC7A5, also called LAT1 (94).”
BackgroundHe, J., Zhang, G.-Y., Pang, Q., Yu, C., Xiong, J., Zhu, J., & Chen, F.-L. (2017) · The FEBS Journal · doi:10.1111/febs.14055 · Cited by 119 · cited 1× · see citing works
“Foam cells are lipidladen macrophages that have taken up oxidized lipids, and this form of macrophage has been associated with disorders including atherosclerosis (69, 70).”
BackgroundVécsei, L., Miller, J. M., Macgarvey, U., & Beal, M. (1992) · Brain Research Bulletin · doi:10.1016/0361-9230(92)90184-y · Cited by 118 · cited 1× · see citing works
“For example, intraperitoneal administration of kynurenine induces dose-dependent increases in rat brain cortical and striatal kynurenic acid concentrations and a dramatic elevation of its extracellular striatal levels (47, 48).”
BackgroundGeng, Y.-J., Azuma, T., Tang, J. X., Hartwig, J. H., Muszynski, M., Wu, Q., Libby, P., & Kwiatkowski, D. J. (1998) · European Journal of Cell Biology · doi:10.1016/s0171-9335(98)80088-5 · Cited by 117 · cited 1× · see citing works
“A plausible explanation of these protein changes could be that kynurenine catabolites induce selective leukocyte apoptosis, because many of these cytoskeletal proteins are primary targets for caspase-3-mediated proteolysis (60, 76).”
BackgroundKita, T., Morrison, P., Heyes, M., & Markey, S. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00955.x · Cited by 116 · cited 1× · see citing works
“Kynurenine metabolism in the brain is reported to be complete and robust under various conditions of immune stimulation, and in the case of LPS infusion into the brain, 98% of kynurenine and Quin in the brain was derived from local synthesis rather than from the blood supply (104).”
BackgroundZhang, L., Овчинникова, О. А., Jönsson, A., Lundberg, A. M., Berg, M., Hansson, G. K., & Ketelhuth, D. F. J. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs175 · Cited by 115 · cited 1× · see citing works
“The kynurenine metabolite 3hydroxyanthranilate has been found to affect foam cell formation by reducing uptake of oxidized low-density lipoprotein by macrophages (71, 72).”
BackgroundFoster, A., Miller, L., Oldendorf, W., & Schwarcz, R. (1984) · Experimental Neurology · doi:10.1016/0014-4886(84)90239-5 · Cited by 114 · cited 1× · see citing works
“Quin is excluded from the brain to the extent possible, including during an immune response (28, 101).”
BackgroundEukaryotic elongation factor 2 controls TNF-α translation in LPS-induced hepatitis
González‐Terán, B., Cortés, J. R., Manieri, E., Matesanz, N., Verdugo, Á., Rodríguez, M. E., González‐Rodríguez, Á., Valverde, Á. M., Martı́n, P., Davis, R. J., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci65124 · Cited by 104 · see citing works
Verrills, N., Walsh, B., Cobon, G., Hains, P., & Kavallaris, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303378200 · Cited by 99 · cited 1× · see citing works
“Heterogeneous nuclear ribonuclear protein K has also been associated with apoptosis (57).”
BackgroundCawthorn, T., Moreno, J. C., Dharsee, M., Tran‐Thanh, D., Ackloo, S., Zhu, P.-H., Sardana, G., Chen, J., Kupchak, P., Jacks, L., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030992 · Cited by 96 · cited 1× · see citing works
“HSP90B1 overexpression has been associated with metastasis of breast cancer (86).”
BackgroundPinteaux, E., Inoue, W., Schmidt, L., Molina-Holgado, F., Rothwell, N., & Luheshi, G. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04559.x · Cited by 96 · see citing works
Uruno, T., Zhang, P.-J., Liu, J.-L., Hao, J., & Zhan, X. (2003) · Biochemical Journal · doi:10.1042/bj20021791 · Cited by 96 · cited 1× · see citing works
“HS1 induces actin polymerization and branching in hematopoietic cells by interacting with the ARP2/3 complex (59).”
BackgroundRole of caspases in immunotoxin-induced apoptosis of cancer cells.
Keppler-Hafkemeyer, A., Brinkmann, U., & Pastan, I. (1998) · Biochemistry · doi:10.1021/bi980995m · Cited by 93 · cited 1×
“Elongation factor 2 inhibition has been associated with apoptosis, but in the present study, we see increases in abundance of this protein (58).”
BackgroundThe role of the kynurenine pathway of tryptophan metabolism in cardiovascular disease
Polyzos, K. A., & Ketelhuth, D. F. J. (2015) · Hämostaseologie · doi:10.5482/hamo-14-10-0052 · Cited by 93 · cited 1× · see citing works
“The kynurenine metabolite 3hydroxyanthranilate has been found to affect foam cell formation by reducing uptake of oxidized low-density lipoprotein by macrophages (71, 72).”
BackgroundThe end of the road for the tryptophan depletion concept in pregnancy and infection
Badawy, A. A.-B., Namboodiri, A. M. A., & Moffett, J. R. (2016) · Clinical Science · doi:10.1042/cs20160153 · Cited by 92 · cited 1× · see citing works
“Yet, the precise nature of the benefits that the kynurenine pathway confers on fitness is a matter of ongoing debate (7, 9, 16, 22, 23).”
BackgroundSelf-citationSSRP1 functions as a co‐activator of the transcriptional activator p63
Zeng, S. X., Dai, M., Keller, D. M., & Lu, H. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf540 · Cited by 89 · cited 1× · see citing works
“However, it has been shown that overexpression of SSRP1 with p63-gamma caused a ∼43% increase of apoptotic cells (61).”
BackgroundFodor, I., Nelson, D., Alegria-Hartman, M., Robbins, K., Langlois, R., Turteltaub, K., Corzett, T., & McCutchen-Maloney, S. (2005) · Bioinform. · doi:10.1093/bioinformatics/bti612 · Cited by 76 · see citing works
Badawy, A., & Evans, M. (1976) · Biochemical Journal · doi:10.1042/bj1580079 · Cited by 73 · cited 1× · see citing works
“Gerbils lack the apoenzyme form of tryptophan dioxygenase and therefore cortisol does not regulate tryptophan catabolism in the liver as it does in certain other species, including rats and humans (68).”
BackgroundSelf-citationTryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention
Badawy, A. A.-B. (2019) · Egyptian Journal of Basic and Clinical Pharmacology · doi:10.32527/2019/101415 · Cited by 73 · see citing works
Self-citationStanford, E., Ramirez-Cardenas, A., Wang, Z.-Y., Novikov, O., Alamoud, K., Koutrakis, P., Mizgerd, J., Genco, C., Kukuruzinska, M., Monti, S., et al. (2016) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0069 · Cited by 72 · cited 1× · see citing works
“AHR agonists also significantly increased migration of squamous cell carcinoma cells in culture (89).”
BackgroundCharacterization 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
Bender, D., Magboul, B., & Wynick, D. (1982) · British Journal of Nutrition · doi:10.1079/bjn19820094 · Cited by 69 · cited 2× · see citing works
“The Km of QPRT is 100 times greater than the normal levels of Quin in the liver, but the Vmax of the enzyme is low, meaning that during times of high tryptophan throughput, some degree of Quin accumulation would be expected (114).”
BackgroundTerakata, 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 · cited 1× · see citing works
“proposed that the TDO-deficient mice could develop normally on a niacin-deficient diet because extra hepatic cells released kynurenine, which the liver took up and converted to Quin and then NAD (117).”
BackgroundGrant, R., Passey, R. J., Matanovic, G., Smythe, G., & Kapoor, V. (1999) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1381 · Cited by 65 · see citing works
Beagles, K. E., Morrison, P., & Heyes, M. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70010281.x · Cited by 65 · cited 1× · see citing works
“During strong immune stimulation with LPS infusion into the brain, the extracellular Quin level, as measured by microdialysis, increased 66-fold (102).”
BackgroundBahri, R., Bollinger, A., Bollinger, T., Orinska, Z., & Bulfone-Paus, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045234 · Cited by 64 · see citing works
Audrito, V., Managò, A., Gaudino, F., Sorci, L., Messana, V. G., Raffaelli, N., & Deaglio, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01720 · Cited by 64 · cited 1× · see citing works
“The effects of excessive kynurenine flux on cancer cell evasion may be another pathology associated with excess tryptophan in the diet (121).”
BackgroundChoroid Plexus Blood-CSF Barrier: Major Player in Brain Disease Modeling and Neuromedicine
Johanson, C. E. (2018) · Journal of Neurology and Neuromedicine · doi:10.29245/2572.942x/2018/4.1194 · Cited by 62 · cited 1× · see citing works
“LPS is known to disrupt the blood–brain barrier (41) and injections into the hippocampus elicit strong immune cell infiltration and microglial activation over the course of 7 or more days (42).”
BackgroundTryptophan, adenosine, neurodegeneration and neuroprotection
Stone, T., Forrest, C., Mackay, G. M., Stoy, N., & Darlington, L. (2007) · Metabolic brain disease · doi:10.1007/s11011-007-9064-3 · Cited by 60 · see citing works
Dynamics of NAD-metabolism: everything but constant
Opitz, C. A., & Heiland, I. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150133 · Cited by 58 · cited 1× · see citing works
“NAD utilized for redox reactions is not consumed, but many enzyme systems such as the PARP reaction utilize NAD as cosubstrate and convert it to nicotinamide and ADP-ribose, thus depleting intracellular supplies (118).”
BackgroundMiller, J. M., Macgarvey, U., & Beal, M. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90186-b · Cited by 53 · cited 1×
“For example, intraperitoneal administration of kynurenine induces dose-dependent increases in rat brain cortical and striatal kynurenic acid concentrations and a dramatic elevation of its extracellular striatal levels (47, 48).”
BackgroundYoshida, R., Oku, T., Imanishi, J., Kishida, T., & Hayaisi, O. (1986) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(86)90038-x · Cited by 51 · see citing works
Moffett, J., Els, T., Espey, M., Walter, S. A., Streit, W. J., & Namboodiri, M. A. A. (1997) · Experimental Neurology · doi:10.1006/exnr.1996.6365 · Cited by 50 · cited 3× · see citing works
“Lectin histochemistry with Griffonia simplicifolia-B4 lectin (GSL-IB4) and double staining with Quin was done as described earlier (27).”
BackgroundMethodSelf-citationOhashi, K., Kawai, S., & Murata, K. (2013) · Eukaryotic Cell · doi:10.1128/ec.00339-12 · Cited by 47 · cited 1× · see citing works
“Quin is released by yeast cells and taken up by other yeast cells where it is converted to NAD (93).”
BackgroundMy life with tryptophan—Never a dull moment
Hayaishi, O. (1993) · Protein Science · doi:10.1002/pro.5560020320 · Cited by 46 · see citing works
Aspects of Tryptophan and Nicotinamide Adenine Dinucleotide in Immunity: A New Twist in an Old Tale
Biefer, H. R. C., Vasudevan, A., & Elkhal, A. (2017) · International Journal of Tryptophan Research · doi:10.1177/1178646917713491 · Cited by 44 · cited 1× · see citing works
“Yet, the precise nature of the benefits that the kynurenine pathway confers on fitness is a matter of ongoing debate (7, 9, 16, 22, 23).”
BackgroundSwiprosin-1 Is a Novel Actin Bundling Protein That Regulates Cell Spreading and Migration
Kwon, M., Park, K. R., Kim, Y.-D., Na, B.-R., Kim, H.-R., Choi, H.-J., Piragyte, I., Jeon, H., Chung, K., Song, W., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071626 · Cited by 43 · cited 1× · see citing works
“Swiprosin 1, which is involved in cortical cytoskeleton dynamics among other functions (63, 64), was also decreased in the spleen after 48 h of kynurenine administration (ratio−1.”
BackgroundMoffett, J., Espey, M., Gaudet, S. J., & Namboodiri, A. (1993) · Brain Research · doi:10.1016/0006-8993(93)91450-7 · Cited by 43 · see citing works
Self-citationChiarugi, A., & Moroni, F. (1999) · Neuropharmacology · doi:10.1016/s0028-3908(99)00048-9 · Cited by 40 · see citing works
Inhibition of allogeneic T-cell response by Kupffer cells expressing indoleamine 2,3-dioxygenase.
Yan, M.-L., Wang, Y.-D., Tian, Y.-F., Lai, Z.-D., & Yan, L. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i5.636 · Cited by 39 · cited 1× · see citing works
“Kupffer cells are resident hepatic macrophages (39), and it has been shown that they respond to IFN-γ by activation of IDO and production of kynurenine (40).”
BackgroundMoffett, J. R., Espey, M., & Namboodiri, M. (1994) · Cell and Tissue Research · doi:10.1007/bf00331364 · Cited by 39 · cited 5× · see citing works
“The methods used for the production, purification, and characterization of the polyclonal Quin antibodies have been described previously (26).”
BackgroundMethodInfluentialSelf-citationLehrmann, E., Molinari, A., Speciale, C., & Schwarcz, R. (2001) · Experimental Brain Research · doi:10.1007/s002210100887 · Cited by 38 · cited 4× · see citing works
“Microglia are fully capable of generating Quin if provided super-physiological levels of the immediate precursor (31), but we observed little or no Quin-IR in microglia after direct injection of LPS into the hippocampus.”
BackgroundMethodInfluentialChen, Y.-R., Kori, R., John, B., & Tan, T. (2001) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1006/bbrc.2001.5862 · Cited by 38 · cited 2×
“HS1 is also a caspase target during apoptosis (60).”
BackgroundMorrison, P., Morishige, G. M., Beagles, K. E., & Heyes, M. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0722135.x · Cited by 38 · cited 2×
“Quin levels in the brain are maintained below blood levels by barriers and transporters (100).”
BackgroundNicotinic Acid Biosynthesis: Control by an Enzyme that Competes with a Spontaneous Reaction
Mehler, A., Yano, K., & May, E. (1964) · Science · doi:10.1126/science.145.3634.817 · Cited by 38 · cited 3×
“production of kynurenine, which is released for uptake by cells of the immune system thus diverting tryptophan metabolism to the immune system, (2) the production of NAD in cells of the immune system for the PARP reaction to DNA damage and other critical functions in immune cells, and (3) the production and release of”
BackgroundMethodAHSA1 regulates proliferation, apoptosis, migration, and invasion of osteosarcoma
Shao, J., Wang, L., Zhong, C. F., Qi, R., & Li, Y. (2015) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2015.11.008 · Cited by 36 · cited 1× · see citing works
“AHSA1 has been reported to regulate proliferation, apoptosis, migration, and invasion of osteosarcoma (85).”
BackgroundEspey, M., Moffett, J. R., & Namboodiri, A. (1995) · Journal of Leukocyte Biology · doi:10.1002/jlb.57.2.199 · Cited by 36 · see citing works
Self-citationSIRT1 regulates lamellipodium extension and migration of melanoma cells.
Kunimoto, R., Jimbow, K., Tanimura, A., Sato, M., Horimoto, K., Hayashi, T., Hisahara, S., Sugino, T., Hirobe, T., Yamashita, T., et al. (2014) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.50 · Cited by 35 · cited 1×
“Interestingly, the NAD-dependent deacetylase enzyme SIRT1 is required for lamellipodia extension and migration of melanoma cells (78).”
BackgroundMoffett, J. R., Blinder, K., Venkateshan, C., & Namboodiri, M. (1998) · Cell and Tissue Research · doi:10.1007/s004410051145 · Cited by 34 · cited 5× · see citing works
“We observed a modest increase in Quin-IR in the liver after high-dose tryptophan (29).”
BackgroundInfluentialSelf-citationHigh protein intake is associated with low plasma NAD+ levels in a healthy human cohort
Seyedsadjadi, N., Berg, J., Bilgin, A. A., Braidy, N., Salonikas, C., & Grant, R. (2018) · PLOS ONE · doi:10.1371/journal.pone.0201968 · Cited by 33 · cited 1× · see citing works
“Interestingly, studies indicate that high protein diets have a negative impact on plasma NAD levels (120).”
BackgroundSu, H.-H., Lin, H.-T., Suen, J.-L., Sheu, C., Yokoyama, K., Huang, S.-K., & Cheng, C.-M. (2016) · Toxicology · doi:10.1016/j.tox.2016.09.019 · Cited by 32 · cited 1× · see citing works
“AHR activation in lung fibroblasts significantly enhanced migration via generation of arachidonic acidmetabolites (88).”
BackgroundEspey, M., Tang, Y., Morse, H., Moffett, J., & Namboodiri, M. A. A. (1996) · AIDS (London) · doi:10.1097/00002030-199602000-00004 · Cited by 32 · cited 1× · see citing works
“We have shown that Quin-IR is increased in a number of different conditions where the immune system is stimulated, in addition to those detailed here, including SIV in monkeys (105), human T-cell lymphotropic virus type 1 infection of human peripheral blood monocytes/macrophages (106), and in a murine AIDS model (107).”
BackgroundSelf-citationRoles of SAMHD1 in antiviral defense, autoimmunity and cancer
Li, M., Zhang, D., Zhu, M., Shen, Y., Wei, W., Ying, S.-C., Korner, H., & Li, J. (2017) · Reviews in Medical Virology · doi:10.1002/rmv.1931 · Cited by 31 · cited 1× · see citing works
“SAM and HD domain-containing protein 1 (SAMHD1) is involved in anti-viral responses (55).”
BackgroundPepelyayeva, Y., Rastall, D. P. W., Aldhamen, Y., O’Connell, P., Raehtz, S., Alyaqoub, F., Blake, M. K., Raedy, A. M., Angarita, A. M., Abbas, A. M., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-30159-5 · Cited by 30 · cited 1× · see citing works
“Mice lacking ERAP1 had reduced numbers of both Tr1-like regulatory T cells and tolerogenic dendritic cells (54), suggesting that increased ERAD1 expression could be associated with increased numbers of these tolerogenic cell types in the spleen in response to kynurenine administration.”
BackgroundMa, M., & Baumgartner, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075577 · Cited by 30 · cited 1×
“Overall, Quin-IR cells in the brain after LPS injection resembled motile macrophages [see (73)].”
BackgroundStructural Basis of Streptococcus pyogenes Immunity to its NAD+ Glycohydrolase Toxin
Smith, C. L., Ghosh, J., Elam, J., Pinkner, J., Hultgren, S., Caparon, M., & Ellenberger, T. (2011) · Structure · doi:10.1016/j.str.2010.12.013 · Cited by 29
Effect of nicotinamide administration on the tryptophan-nicotinamide pathway in humans.
Fukuwatari, T., & Shibata, K. (2007) · International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition · doi:10.1024/0300-9831.77.4.255 · Cited by 28 · cited 1× · see citing works
“However, the tryptophan-to-NAD pathway operates independently of niacin supply (115).”
BackgroundTorigoe, M., Maeshima, K., Ozaki, T., Omura, Y., Gotoh, K., Tanaka, Y., Ishii, K., & Shibata, H. (2018) · Modern Rheumatology · doi:10.1080/14397595.2018.1510822 · Cited by 27
Grant, R. S. (2018) · International Journal of Tryptophan Research · doi:10.1177/1178646917751636 · Cited by 22 · cited 2× · see citing works
“However, a PARP inhibitor resulted in an increase in NAD levels in macrophages and INF-γ plus the PARP inhibitor further increased NAD levels (14).”
BackgroundSwiprosin‐1: Its Expression and Diverse Biological Functions
Thylur, R. P., Gowda, R., Mishra, S., & Jun, C. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26199 · Cited by 20 · cited 1× · see citing works
“Swiprosin 1, which is involved in cortical cytoskeleton dynamics among other functions (63, 64), was also decreased in the spleen after 48 h of kynurenine administration (ratio−1.”
BackgroundMoffett, J., Espey, M., Saito, K., & Namboodiri, M. A. A. (1994) · Journal of Neuroimmunology · doi:10.1016/0165-5728(94)90232-1 · Cited by 19 · see citing works
Self-citationXie, J.-L., Damme, P. V., Fang, D., & Proud, C. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ac119.008036 · Cited by 18 · cited 16× · see citing works
“Interestingly, heat shock protein 90B1 (HSP90B1; also known as endoplasmin), which is associated with the HSP90 chaperone complex, was expressed at an increased ratio +1.43.”
BackgroundInfluentialNamboodiri, A., Venkateshan, C. N. S., Narayanan, R., Blinder, K., Moffett, J. R., Gajdusek, D., Gravell, M., & Gibbs, C. J. (1996) · Journal of Neurovirology · doi:10.3109/13550289609146910 · Cited by 17 · see citing works
Self-citationVenkateshan, C. N., Narayanan, R., Espey, M., Moffett, J. R., Gajdusek, D., Gibbs, C. J., & Namboodiri, M. (1996) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.93.4.1636 · Cited by 15 · cited 1× · see citing works
“We have shown that Quin-IR is increased in a number of different conditions where the immune system is stimulated, in addition to those detailed here, including SIV in monkeys (105), human T-cell lymphotropic virus type 1 infection of human peripheral blood monocytes/macrophages (106), and in a murine AIDS model (107).”
BackgroundSelf-citationHsieh, C.-L., Huang, H.-M., Hsieh, S.-Y., Zheng, P.-X., Lin, Y.-S., Chiang-Ni, C., Tsai, P., Wang, S., Liu, C.-C., & Wu, J.-J. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01733 · Cited by 13 · see citing works
Increased conversion ratio of tryptophan to niacin in severe food restriction.
Shibata, K., Kondo, T., & Miki, A. (1998) · Bioscience, biotechnology and biochemistry · doi:10.1271/bbb.62.580 · Cited by 13 · cited 1×
“When tryptophan is required for NAD synthesis due to a poor diet or prolonged fasting, the liver activates TDO and tryptophan is catabolized through the kynurenine pathway to NAD (116).”
BackgroundST13, a proliferation regulator, inhibits growth and migration of colorectal cancer cell lines
Bai, R., Shi, Z.-W., Zhang, J.-W., Li, D., Zhu, Y.-L., & Zheng, S. (2012) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1200037 · Cited by 12 · cited 1×
“High expression levels of ST13 are associated with reduced cell migration and proliferation of colorectal cancer cells (62).”
BackgroundQuinolinic acid excretion and metabolism in man.
Sarett, H. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50919-4 · Cited by 9 · cited 1×
“Periphery In humans, Quin is excreted in the urine and the level in urine increases with increasing oral doses of tryptophan (98).”
BackgroundMitogen-Induced Interferon Gamma Production in Human Whole Blood: The Effect of Heat and Cations
Nam, J.-H., Cha, B., Park, J.-Y., Abekura, F., Kim, C.-H., & Kim, J.-R. (2019) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201020666190528093432 · Cited by 7 · cited 1× · see citing works
“Further, PWM is one of the more potent inducers of INF-γ release (37).”
BackgroundGlycoconjugate with terminal galactose
Honda, T., Schulte, B. A., & Spicer, S. (2004) · Histochemistry · doi:10.1007/bf00501913 · Cited by 3
Flagged first, then by citations
4 of the 124 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [1]Henderson LM. Quinolinic acid metabolism; replacement of nicotinic acid for the growth of the rat and Neurospora. J Biol Chem. (1949) 181: 677– 85. 15393785
Cited by
Sorted by citations
Microglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365 · see citing works
Salminen, A. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101573 · Cited by 197 · see citing works
“Currently, it is not known whether its role is to replenish the reduced content of NAD during chronic inflammation (Moffett et al., 2020).”
BackgroundGreathouse, K. L., & Wyatt, M. (2021) · Nutrients · doi:10.3390/nu13041189 · Cited by 111 · see citing works
“Therefore, Kyn pathway activity is amplified under inflammatory conditions, in part due to an NAD+ requirement for increased energy demands in the immune cells and to implement immunomodulatory functions [35].”
BackgroundKynurenine Pathway Metabolites as Biomarkers in Alzheimer’s Disease
Liang, Y., Xie, S., He, Y., Xu, M., Qiao, X., Zhu, Y. H., & Wu, W. (2022) · Disease Markers · doi:10.1155/2022/9484217 · Cited by 86 · see citing works
A multimodal atlas of tumour metabolism reveals the architecture of gene–metabolite covariation
Benedetti, E., Liu, E. M., Tang, C., Kuo, F., Büyüközkan, M., Park, T., Park, J., Correa, F., Hakimi, A. A., Intlekofer, A. M., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00817-8 · Cited by 76 · see citing works
Jennings, M. R., Munn, D. H., & Blazeck, J. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003013 · Cited by 63 · see citing works
Wang, Y., Zhang, Y., Wang, W., Zhang, Y., Dong, X., & Liu, Y. (2025) · Metabolites · doi:10.3390/metabo15030210 · Cited by 56 · see citing works
An Emerging Cross-Species Marker for Organismal Health: Tryptophan-Kynurenine Pathway
Jamshed, L., Debnath, A., Jamshed, S., Wish, J. V., Raine, J. C., Tomy, G. T., Thomas, P. J., & Holloway, A. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116300 · Cited by 54 · see citing works
Sun, S.-P., Zhang, J., Li, H.-X., Du, Y.-Y., Li, S., Li, A., Suo, X., Wang, Y., & Sun, Q. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.113880 · Cited by 48 · see citing works
The Kynurenine Pathway in Gut Permeability and Inflammation
Kearns, R. (2024) · Inflammation · doi:10.1007/s10753-024-02135-x · Cited by 37 · see citing works
“This variability in neuronal sensitivity may partly explain the elevated levels of neurodegeneration observed in these regions in AD patients, which correlates with increased QUIN levels and associated inflammatory processes [83].”
Enzymology of extracellular NAD metabolism
Gasparrini, M., Sorci, L., & Raffaelli, N. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03742-1 · Cited by 51 · see citing works
“In plasma, QA circulates at low micromolar level, but it significantly increases following infections or immune challenge [40], likely deriving from cells of the immune system that accumulate substantial levels of QA upon stimulation [41].”
BackgroundBadawy, A. A. ‐. (2023) · Bioscience Reports · doi:10.1042/bsr20230595 · Cited by 40 · see citing works
“The group of J R Moffett (see [15] and references cited therein) demonstrated accumulation of QA as a marker of KP enzymatic activities in immune cells, especially phagocytes and antigen-presenting cells (monocytes/macrophages, dendritic cells, microglia, Langerhans and Kupffer cells).”
BackgroundSelf-citationNAD+ Metabolism, Metabolic Stress, and Infection
Groth, B., Venkatakrishnan, P., & Lin, S.-J. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.686412 · Cited by 41 · see citing works
“This suggests that the brain balances the production of immunosuppressive KYN metabolites and the restoration of depleted NAD levels with the neurotoxic QA (Moffett et al., 2020).”
BackgroundImmunotherapy of COVID-19 with poly (ADP-ribose) polymerase inhibitors: starting with nicotinamide
Badawy, A. A. ‐. (2020) · Bioscience Reports · doi:10.1042/bsr20202856 · Cited by 39 · see citing works
Self-citationParveen, S., Shen, J., Lun, S., Zhao, L., Alt, J., Koleske, B. N., Leone, R. D., Rais, R., Powell, J. D., Murphy, J. R., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43304-0 · Cited by 42 · see citing works
“Kynurenine metabolism also generates quinolinic acid, a potent neurotoxin (if accumulated), which is essential for the de novo synthesis of NAD +64 .”
Neuroimmunometabolism: A New Pathological Nexus Underlying Neurodegenerative Disorders
Mitra, S., Banik, A., Saurabh, S., Maulik, M., & Khatri, S. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.0998-21.2022 · Cited by 44 · see citing works
“Tryptophan is converted into kynurenine and down-stream effector molecules by indoleamine-2,3 dioxygenase, a rate-limiting enzyme whose expression is elevated during inflammation, including the brain (Kwidzinski and Bechmann, 2007; O ’ Neill et al., 2016; Moffett et al., 2020).”
Dysregulated Metabolic Pathways in Subjects with Obesity and Metabolic Syndrome
Mir, F., Ullah, E., Mall, R., Iskandarani, A., Samra, T., Cyprian, F., Parray, A., Alkasem, M., Abdalhakam, I., Farooq, F., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179821 · Cited by 28 · see citing works
Zhao, J., Chen, J., Wang, C., Liu, Y., Li, M., Li, Y., Li, R., Han, Z., Wang, J., Chen, L., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010366 · Cited by 34 · see citing works
“The previous study also found that Ca and its major downstream effector, CaMKII, are important for immune cells’ functions, and CaMKII could significantly enhance the production of IFN-α/β in macrophages [37,58].”
BackgroundLai, W., Huang, Z., Li, S., Li, X.-G., & Luo, D. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.109840 · Cited by 28 · see citing works
He, S., Granot-Hershkovitz, E., Zhang, Y., Bressler, J., Tarraf, W., Yu, B., Huang, T.-Y., Zeng, D.-L., Wassertheil-Smoller, S., Lamar, M., et al. (2021) · medRxiv · doi:10.1002/dad2.12259 · Cited by 26 · see citing works
Immunometabolic coevolution defines unique microenvironmental niches in ccRCC
Tang, C., Xie, A., Liu, E. M., Kuo, F., Kim, M., DiNatale, R. G., Golkaram, M., Chen, Y., Gupta, S., Motzer, R. J., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.06.005 · Cited by 24 · see citing works
Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells
Kolotyeva, N. A., Groshkov, A. A., Rozanova, N. A., Berdnikov, A. K., Novikova, S. V., Komleva, Y. K., Salmina, A. B., Illarioshkin, S. N., & Пирадов, М. А. (2024) · Biomolecules · doi:10.3390/biom14121556 · Cited by 22 · see citing works
“Some studies [84,85] highlight an association of the pathogenesis of epilepsy, Huntington’s disease, and stroke with aberrant activity of quinolinate phosphoribosyl transferase (QPRT).”
The roles of the kynurenine pathway in COVID-19 neuropathogenesis
Dehhaghi, M., Heydari, M., Panahi, H. K. S., Lewin, S. R., Heng, B., Brew, B. J., & Guillemin, G. J. (2024) · Infection · doi:10.1007/s15010-024-02293-y · Cited by 24 · see citing works
“In addition to the neurotoxic effects of QUIN mentioned above, excessive levels of QUIN can negatively affect the NAD + metabolism [176, 177].”
BackgroundNataraj, B. H., Kumari, M., Nagpal, R., Ali, S. A., & Behare, P. V. (2023) · Food Bioscience · doi:10.1016/j.fbio.2023.103101 · Cited by 24 · see citing works
Kynurenine Pathway Metabolites as Potential Biomarkers in Chronic Pain
Auyeung, A., Wang, H. C., Aravagiri, K., & Knezevic, N. (2023) · Pharmaceuticals · doi:10.3390/ph16050681 · Cited by 20 · see citing works
Angioni, S. L., Congiu, F., Vitale, S. G., D’Alterio, M. N., Noto, A., Monni, G., Santoru, M. L., Fanos, V., Murgia, F., & Atzori, L. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12030922 · Cited by 19 · see citing works
“It has been proposed that, during inflammation, tryptophan metabolism occurs mainly in immune cells, while in homeostatic/healthy conditions, most TRP degradation occurs in the liver [103].”
BackgroundWang, Z., Yin, L.-P., Qi, Y., Zhang, J.-L., Zhu, H.-Y., & Tang, J.-G. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.934786 · Cited by 20 · see citing works
Anderson, E., Jin, Y., Shih, A., Arazi, A., Goodwin, S., Roeser, J., Furie, R. A., Aranow, C. B., Volpe, B. T., Diamond, B., et al. (2022) · Lupus Science & Medicine · doi:10.1136/lupus-2022-000808 · Cited by 24 · see citing works
Kurniati, D., Hirai, S., & Egashira, Y. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e12743 · Cited by 19 · see citing works
Xia, H.-H., & Huang, J. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1707850 · Cited by 17 · see citing works
Tang, Y., Fu, X., Li, X., Fang, H., Yang, F., Wang, R., Yin, H.-H., Chen, X., Luo, R., Zang, N., et al. (2025) · Journal of Infection · doi:10.1016/j.jinf.2025.106525 · Cited by 16 · see citing works
States of quinolinic acid excess in urine: A systematic review of human studies
Saade, M., Clark, A. J., & Parikh, S. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1070435 · Cited by 17 · see citing works
“Additionally, there is evidence that urinary quinolinic acid levels correspond with systemic levels (15).”
BackgroundSandvig, H. V., Aam, S., Alme, K., Lydersen, S., Ueland, P. M., Ulvik, A., Wethal, T., Saltvedt, I., & Knapskog, A. (2024) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2024.02.030 · Cited by 16 · see citing works
“In the brain following stroke, QA is produced by activated microglia and by infiltrating macrophages (Lugo-Huitr ´ on et al., 2013; Moffett et al., 2020), while hepatocytes and peripheral immune cells contribute to plasma QA (Moffett et al., 2020).”
BackgroundMethod“Kynurenine switch” and obesity
Shestopalov, A., Shatova, O., Karbyshev, M. S., Gaponov, A. M., Moskaleva, N., Appolonova, S., Tutelyan, A., Makarov, V., Yudin, S., & Roumiantsev, S. (2022) · Bulletin of Siberian Medicine · doi:10.20538/1682-0363-2021-4-103-111 · Cited by 15
“Intracellular levels of quinolinic acid increase in response to immune stimulation by lipopolysaccharide in macrophages, microglia, dendritic cells, and other cells of the immune system [8].”
BackgroundInfluentialSuhre, K., Dadhania, D. M., Lee, J. R., Muthukumar, T., Chen, Q., Gross, S. S., & Suthanthiran, M. (2021) · Metabolites · doi:10.3390/metabo11080533 · Cited by 14 · see citing works
“Quinolinate is an intermediate metabolite in the tryptophan metabolism contributing to the de novo biosynthesis of nicotinamide adenine dinucleotide (NAD+), which is pivotal to energy and critical cellular processes [10].”
BackgroundGarcía-Flores, L., Green, C. L., Mitchell, S., Promislow, D., Lusseau, D., Douglas, A., & Speakman, J. (2021) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2101977118 · Cited by 14 · see citing works
Pei, L., Fukutani, K. F., Tibúrcio, R., Rupert, A. W., Dahlstrom, E. W., Galindo, F., Laidlaw, E., Lisco, A., Manion, M. M., Andrade, B. B., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.693074 · Cited by 17 · see citing works
“HIV infected ART-naïve patients with CD4+ T cell count 100 cells/mL were enrolled in a prospective observational study at the National Institutes of Health [PET Imaging and lymph node assessment of IRIS in persons with AIDS (PANDORA) June 2021 | Volume 12 | Article 693074 NCT02147405].”
BackgroundInfluentialImmunological Interfaces: The COVID-19 Pandemic and Depression
Perlmutter, A. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.657004 · Cited by 17 · see citing works
“Notably, IDO is highly expressed in immune cells (93) and compared to TDO it is far more responsive to immunological signals (94).”
BackgroundBasson, C., Serem, J., Hlophe, Y., & Bipath, P. (2023) · Cell Biochemistry and Function · doi:10.1002/cbf.3843 · Cited by 12 · see citing works
“insufficient dietary niacin intake or a compromised immune system, tryptophan is catabolized for NAD de novo synthesis.(12,13) Tryptophan is an essential amino acid in mammals(14) and the least abundant of all essential amino acids.”
BackgroundStructure, mechanism and inhibition of anthranilate phosphoribosyltransferase
Scully, T. W., Jiao, W., Mittelstädt, G., & Parker, E. (2023) · Philosophical Transactions of the Royal Society of London. Biological Sciences · doi:10.1098/rstb.2022.0039 · Cited by 12 · see citing works
Elevated serum levels of kynurenine pathway metabolites in patients with Behçet disease
Onmaz, D. E., Tezcan, D., Abuşoğlu, S., Sivrikaya, A., Kuzu, M., Yerlikaya, F. H., Yi̇lmaz, S., & Ünlü, A. (2022) · Amino Acids · doi:10.1007/s00726-022-03170-4 · Cited by 13 · see citing works
Xing, J.-H., Li, H.-B., Xia, H.-G., Xia, L.-L., & Zhao, H.-Z. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1698647 · Cited by 11 · see citing works
Aarsland, T. I. M., Instanes, J. T., Posserud, M.-B. R., Ulvik, A., Keßler, U., & Haavik, J. (2022) · Pharmaceuticals · doi:10.3390/ph15111439 · Cited by 12 · see citing works
“IDO1, on the other hand, is induced by pro-inflammatory cytokines, especially interferon gamma (IFN-γ) [90].”
BackgroundInfluentialEndosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities
Perl, A. (2025) · Nature Reviews Rheumatology · doi:10.1038/s41584-025-01336-4 · Cited by 9 · see citing works
Metabolomics Profiling of Stages of Coronary Artery Disease Progression
Anlar, G., Anwardeen, N., Alashmar, S., Pedersen, S., Elrayess, M. A., & Zeidan, A. (2024) · Metabolites · doi:10.3390/metabo14060292 · Cited by 10 · see citing works
“These revelations augment our understanding of the metabolic dysregulations that contribute to atherosclerosis and could potentially direct subsequent investigations and the development of precise treatments aimed at reducing cardiovascular risks.”
BackgroundLonati, C., Berezhnoy, G., Lawler, N. G., Masuda, R., Kulkarni, A., Sala, S., Nitschke, P., Zizmare, L., Bucci, D., Cannet, C., et al. (2023) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2023-1017 · Cited by 10 · see citing works
Exploring the role of riboflavin in swine well-being: a literature review
Shastak, Y., & Pelletier, W. (2024) · Porcine Health Management · doi:10.1186/s40813-024-00399-1 · Cited by 9
Wang, B., Yang, W., Tong, Y., Sun, M., Quan, S., Zhu, J., Zhang, Q., Qin, Z., Ni, Y., Zhao, Y., et al. (2023) · Journal of Medical Virology · doi:10.1002/jmv.29219 · Cited by 9 · see citing works
“28,29 The kynurenine pathway was activated after Omicron SARS ‐ CoV ‐ 2 infection and several metabolites in kynurenine metabolism pathway including N ‐ formylkynurenine, kynurenine, and quinolinate significantly increased (Figure 3E and Table S3).”
BackgroundGliozzi, M., Coppoletta, A. R., Cardamone, A., Musolino, V., Carresi, C., Nucera, S., Ruga, S., Scarano, F., Bosco, F., Guarnieri, L., et al. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107087 · Cited by 9 · see citing works
Gusdon, A., Savarraj, J. P. J., Feng, D., Starkman, A., Li, G., Bodanapally, U. K., Zimmerman, W., Ryan, A. S., Choi, H., & Badjatia, N. (2024) · Scientific Reports · doi:10.1038/s41598-024-64666-5 · Cited by 7 · see citing works
“Quinolinate can be used to synthesize nicotinamide adenine dinucleotide (NAD + ), which is depleted in response to proinflammatory stimuli 44 .”
BackgroundParveen, S., Shen, J. Y. Q., Lun, S., Zhao, L., Koleske, B., Leone, R., Rais, R., Powell, J. D., Murphy, J., Slusher, B., et al. (2023) · bioRxiv · doi:10.1101/2023.02.23.529704 · Cited by 7
Basson, C., Serem, J., Bipath, P., & Hlophe, Y. (2024) · Cell Biology International · doi:10.1002/cbin.12163 · Cited by 6
“…active kynurenine metabolites are formed through tryptophan catabolism via the kynurenine pathway (Macchiarulo et al., 2009), namely due to insufficient dietary niacin consumption or in immunomodulatory conditions, such as cancer (Basson et al., 2023a; Mehmel et al., 2020; Moffett et al., 2020).”
BackgroundLi, J., Zhao, Y.-F., Mi, J., Yi, Z., Holyoak, G. R., Wu, R.-Z., Wang, Z., Zhu, Y.-P., & Zeng, S. (2023) · Journal of Equine Veterinary Science · doi:10.2139/ssrn.4252551 · Cited by 6
Zanella, L. G. F. D. A. B. D. (2022) · Journal of Infectious Diseases and Epidemiology · doi:10.23937/2474-3658/1510243 · Cited by 4 · see citing works
“TGF-β1induced Th17 differentiation can occur without IL-6 if there is sufficient IL-21[14-20] (Figure 3).”
BackgroundInfluentialChen, L., Chen, H.-Y., Li, Q., Ma, J., Feng, Y., Zhang, S., Han, Y., Pan, J., Zhang, M.-J., Sun, K., et al. (2025) · Aging · doi:10.18632/aging.206250 · Cited by 5 · see citing works
Wang, Y.-X., Leung, E., & Tomek, P. (2024) · bioRxiv · doi:10.1101/2024.11.15.623703 · Cited by 5
Verma, K., Amitabh, Prasad, D., Reddy, M. P., & Kohli, E. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00632 · Cited by 5 · see citing works
Larsen, M. C., Rondelli, C. M., Almeldin, A., Song, Y.-S., N'jai, A., Alexander, D. L., Forsberg, E., Sheibani, N., & Jefcoate, C. R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316884 · Cited by 5 · see citing works
Diallo, D., Sun, S., Somboro, A. M., Baya, B., Koné, A., Diarra, B., Nantoume, M., Koloma, I., Diakité, M., Holl, J., et al. (2023) · Research Square · doi:10.3389/fimmu.2025.1561459 · Cited by 5
“Quinolinate (quinolinic acid) is known as a marker for kynurenine in the tryptophan pathway (27).”
Michieletto, J., Delvaux, A., Chu-Van, E., Junot, C., Fenaille, F., & Castelli, F. (2023) · Metabolites · doi:10.3390/metabo13030311 · Cited by 5 · see citing works
“More recently, tryptophan/kynurenine derivatives have been largely described as immunoregulators: tryptophan breakdown appears to be associated with the maintenance of tolerance and quinolinic acid acts as a precursor of nicotinamide adenine dinucleotide [22,23].”
BackgroundWang, N.-N., Pan, D., Wang, X., Su, M., Wang, X., Yan, Q.-Y., Sun, G.-J., & Wang, S.-K. (2022) · Nutrients · doi:10.3390/nu14224916 · Cited by 5 · see citing works
Notarangelo, F. M., & Schwarcz, R. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15416 · Cited by 5 · see citing works
“Moreover, as in the fetal brain, and possibly due to its rapid conversion to NAD + (Moffett et al., 2020), LPS treatment did not raise brain QUIN levels acutely in the adult animals, as also previously reported (Clark, Notarangelo, et al., 2019).”
BackgroundThe role of kynurenine and kynurenine metabolites in psoriasis
Akyürek, F., Akyürek, F. T., & Şengül, F. (2024) · Turkish Journal of Biochemistry · doi:10.1515/tjb-2024-0135 · Cited by 4 · see citing works
Chen, Y.-Z., Jiang, B., Qu, C., Jiang, C., Zhang, C., Wang, Y.-X., Chen, F., Sun, X.-T., Su, L., & Luo, Y. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1424957 · Cited by 4 · see citing works
Rostaminejad, M., Rostami, A. M., Behzad‐Behbahani, A., Dehbidi, G. R., & Kalantari, T. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06935-4 · Cited by 5 · see citing works
Fongsaran, C., Dineley, K. T., Paessler, S., & Cisneros, I. E. (2024) · Pathogens · doi:10.3390/pathogens13050397 · Cited by 3 · see citing works
Yan, J., Zhang, J., Ye, X., Wang, H.-H., Li, H., Li, W.-R., Wu, H., & Zhao, W. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71243 · Cited by 3
“232,233 Large-scale metabolomics studies revealed significantly elevated kynurenine-to-tryptophan (Kyn/Trp) ratios in patients withADandmildcognitiveimpairment(MCI)comparedtohealthycon-trols, and these progressively increased with disease severity.”
Wang, T.-T., Jepsen, J. M., Vinding, R., Brustad, N., Chen, L., Hernández-Lorca, M., Ali, M., Rosenberg, J., Mohammadzadeh, P., Widdowson, M., et al. (2026) · Nature Communications · doi:10.1038/s41467-025-68115-3 · Cited by 3 · see citing works
Lejonberg, C., Czuba, T., Egerstedt, A., Ghosh, N., Celik, S., Ljungman, C. E. A., Lundgren, J., Rådegran, G., Gidlöf, O., & Smith, J. G. (2025) · Journal of the American Heart Association · doi:10.1161/jaha.124.039248 · Cited by 4 · see citing works
Gao, Y., Gao, C.-S., & Nie, H.-T. (2025) · Environmental Research · doi:10.1016/j.envres.2025.121687 · Cited by 3
Role of Tryptophan Metabolites and Short-Chain Fatty Acids in Pathogenesis of Autoimmune Diseases
Shatova, O. P., Yagodkina, E. M., Kaydoshko, S. S., Zabolotneva, A. A., & Shestopalov, A. V. (2023) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093023040270 · Cited by 3 · see citing works
D'Elia, Z. L. G. F. D. A. B., & Marques, B. M. (2021) · Journal of Infectious Diseases and Epidemiology · doi:10.23937/2474-3658/1510234 · Cited by 5 · see citing works
Lindahl, J., Veibäck, G. S., Suneson, K., Blanking, W., Tjernberg, J., Ståhl, D., Wiman, Å., Ventorp, F., Erhardt, S., & Lindqvist, D. (2026) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2026.101221 · Cited by 3 · see citing works
“NAD + is one of the body's most prevalent metabolites, primarily due to its critical role in energy production, and as most NAD + is derived from reactions recycling NAA rather than from KP activity (Moffett et al., 2020; Xie et al., 2020).”
The Kynurenine Pathway in Psoriasis: Mechanisms and Therapeutic Opportunities
Huang, S., Bai, Y.-P., & Duan, X.-W. (2025) · Inflammation · doi:10.1007/s10753-025-02339-9 · Cited by 2 · see citing works
“Experiments suggest that QUIN may synergistically promote inflammatory cell infiltration and epidermal barrier disruption through activa - tion of keratinocyte inflammatory mediators and immune cell chemotaxis [90, 91].”
A Multimodal Atlas of Tumor Metabolism Reveals the Architecture of Gene-Metabolite Co-regulationPreprint
Benedetti, E., Liu, E. M., Tang, C., Kuo, F., Büyüközkan, M., Park, T., Park, J., Correa, F., Hakimi, A. A., Intlekofer, A. M., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.23.517549 · Cited by 4 · see citing works
Plasma Metabolomics in a Nonhuman Primate Model of Abdominal Radiation Exposure
Jun, S.-R., Boerma, M., Udaondo, Z., Richardson, S., Thrall, K., Miousse, I., Seng, J., Pathak, R., & Hauer-Jensen, M. (2021) · Metabolites · doi:10.3390/metabo11080540 · Cited by 2 · see citing works
Disruption of myocardial NAD⁺ balance in heart failure: Mechanisms and therapeutic opportunities
Sundaresan, S., & Hottiger, M. O. (2026) · Disease and Therapeutics · doi:10.1016/j.dist.2026.100008 · Cited by 1 · see citing works
Chen, M., Lu, Z., Zhang, T., Li, G., Zheng, Q., & Zhang, T. (2026) · Natural Products and Bioprospecting · doi:10.1007/s13659-025-00582-z · Cited by 1 · see citing works
“Qui-nolinate is a key metabolite in the kynurenine pathway of tryptophan catabolism breakdown [28].”
Wang, B.-E., Zhen, D., Wei, J., Ding, L., Ding, W.-Y., Portha, B., & Liu, J. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178065 · Cited by 1 · see citing works
Metabolic Effects of Healing Touch During Cervical Cancer Treatment: An Exploratory Analysis
van Wietmarschen, H., Área-Gómez, E., Picard, M. A., Goodheart, M. J., Sood, A. K., & Lutgendorf, S. K. (2025) · Integrative Cancer Therapies · doi:10.1177/15347354251367793 · Cited by 1 · see citing works
“47 The mito-chondria-related kynurenine pathway is the only pathway responsible for the synthesis of the metabolic cofactor nicotinamide adenine dinucleotide (NAD + , of which kynurenine is a precursor), which decreases with aging and whose supplementation improves resilience to age-related…”
Liu, L. (2026) · Reviews in Medical Virology · doi:10.1002/rmv.70207
Virobiome-mediated regulation of microbiota–gut–brain axis signaling and neuroimmune homeostasis
Afkhamian, A., Natanzi, A. S., Jafaridarabjerdi, M., Aghaei, S., Haghjou, A., Shafiei, M., Bashkandi, A. H., Shahraki, S., Reiter, R. J., Kashani, H. H., et al. (2026) · Cell Communication and Signaling · doi:10.1186/s12964-026-03067-9
“Its production is tightly regulated by the enzyme IDO, which is upregulated during inflammation and microbial dysbiosis [223].”
Tao, G.-Y., Wang, L.-Z., Du, H.-Z., Zeng, Z.-H., & Lei, L.-M. (2026) · Journal of Pain Research · doi:10.2147/jpr.s619982
“Within this moderate-support tier, QPRT remains biologically interesting because it encodes quinolinate phosphoribosyltransferase, a downstream enzyme in the kynurenine pathway, 20 and kynurenine-pathway metabolites have repeatedly been linked to neuroinflammatory and chronic pain states.”
Evaluation of the Relationship Between Bruxism and Tryptophan Metabolites: A Case-Control Study.
Gürses, G., & Ünlü, A. (2026) · Journal of Oral Rehabilitation · doi:10.1111/joor.70174
The Association Between Metabolomic and Usual Biochemical Data Helps to Detect Insulin Resistance
Pimenta, F. S., Conde, C., Rodrigues, R. R., Campagnaro, B. P., Pereira, T. M. C., Campos-Toimil, M., Meyrelles, S. S., & Vasquez, E. C. (2026) · Biomedicines · doi:10.3390/biomedicines14020393
“Our findings support the concept that disturbances in tryptophan metabolism can be identified early through the analysis of organic acidurias [20,38,42], providing insights into immunometabolic dysregulation prior to the clinical manifestation of disease and enabling opportunities for primary…”
Li, Y., Sági-Kiss, V., James, E. N., Dokal, I., Parkinson, E. K., & Bundy, J. G. (2024) · Haematologica · doi:10.3324/haematol.2023.284721
“…15 kynurenine, 15 N-acetylleucine, 16 norvaline and paraxanthine 17 ) as well as paradoxically three neurotoxic ones (N-acetylisoleucine, quinolate 15 and quinolate carboxylate 15 ) was observed in DC patient plasma, indicating a possible link between telomere dysfunction and neuronal function.”
BackgroundGusdon, A., Savarraj, J. P. J., Feng, D., Starkman, A., Li, G., Bodanapally, U. K., Zimmerman, W., Ryan, A. S., Choi, H., & Badjatia, N. (2023) · Research Square · doi:10.21203/rs.3.rs-3600439/v1
“Quinolinate can be used to synthesize nicotinamide adenine dinucleotide (NAD + ), which is depleted in response to proin�ammatory stimuli 41 .”
Shatova, O. P., Yagodkina, E. M., Kaydoshko, S. S., Zabolotneva, A. A., & Shestopalov, A. V. (2023) · Российский физиологический журнал им И М Сеченова · doi:10.31857/s0869813923080095 · Cited by 1 · see citing works
Elevated serum levels of kynurenine pathway metabolites in Behçet's patientsPreprint
Onmaz, D., Tezcan, D., Sivrikaya, A., Abuşoğlu, S., Kuzu, M., Yerlikaya, F., Yılmaz, S., & Ünlü, A. (2021) · Research Square · doi:10.21203/rs.3.rs-987705/v1
- Authors
- Moffett, J. R., Arun, P., Puthillathu, N., Vengilote, R., Ives, J. A., Badawy, A. A.-B., & Namboodiri, A. M.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- Samueli Institute (US)
- Corresponding author
- Moffett, John R.
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2020-02-21
- Volume
- 11
- Pages
- 31-31
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC7047773
- OpenAlex
- W3007394158
- Cited by
- 89
- References
- 124
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 15 · 2023: 19 · 2022: 19 · 2021: 13 · 2020: 2
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- quinolinate, kynurenine pathway, tryptophan catabolism, NAD+ synthesis, inflammation, infection, lipopolysaccharide, pokeweed mitogen, immune cells, cell motility, phagocytosis, HSP90, aryl hydrocarbon receptor, sirtuins, poly(ADP-ribosyl)ation
- MeSH terms
- Animals, Cell Movement, Gerbillinae, Hippocampus, Immunity, Inflammation, Kynurenine, Lipopolysaccharides, Liver, Male, Mice, Inbred C57BL, NAD, Pokeweed Mitogens, Poly(ADP-ribose) Polymerases, Spleen, Tryptophan, Biomarkers, Quinolinic Acid, HSP90 Heat-Shock Proteins, Indoleamine-Pyrrole 2,3,-Dioxygenase, Mice, Rats
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
