Kynurenine pathway metabolites in humans: disease and healthy States - PubMed (original) (raw)
Kynurenine pathway metabolites in humans: disease and healthy States
Yiquan Chen et al. Int J Tryptophan Res. 2009.
Abstract
Tryptophan is an essential amino acid that can be metabolised through different pathways, a major route being the kynurenine pathway. The first enzyme of the pathway, indoleamine-2,3-dioxygenase, is strongly stimulated by inflammatory molecules, particularly interferon gamma. Thus, the kynurenine pathway is often systematically up-regulated when the immune response is activated. The biological significance is that 1) the depletion of tryptophan and generation of kynurenines play a key modulatory role in the immune response; and 2) some of the kynurenines, such as quinolinic acid, 3-hydroxykynurenine and kynurenic acid, are neuroactive. The kynurenine pathway has been demonstrated to be involved in many diseases and disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, AIDS dementia complex, malaria, cancer, depression and schizophrenia, where imbalances in tryptophan and kynurenines have been found. This review compiles most of these studies and provides an overview of how the kynurenine pathway might be contributing to disease development, and the concentrations of tryptophan and kynurenines in the serum, cerebrospinal fluid and brain tissues in control and patient subjects.
Figures
Figure 1.
A schematic diagram of the kynurenine pathway.
Figure 2.
Drugs targeting the kynurenine pathway—inhibitors and analogues.
Similar articles
- Effects of immune activation on quinolinic acid and neuroactive kynurenines in the mouse.
Saito K, Markey SP, Heyes MP. Saito K, et al. Neuroscience. 1992 Nov;51(1):25-39. doi: 10.1016/0306-4522(92)90467-g. Neuroscience. 1992. PMID: 1465184 - Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease.
Heyes MP, Saito K, Crowley JS, Davis LE, Demitrack MA, Der M, Dilling LA, Elia J, Kruesi MJ, Lackner A, et al. Heyes MP, et al. Brain. 1992 Oct;115 ( Pt 5):1249-73. doi: 10.1093/brain/115.5.1249. Brain. 1992. PMID: 1422788 - Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients.
Heyes MP, Brew BJ, Saito K, Quearry BJ, Price RW, Lee K, Bhalla RB, Der M, Markey SP. Heyes MP, et al. J Neuroimmunol. 1992 Sep;40(1):71-80. doi: 10.1016/0165-5728(92)90214-6. J Neuroimmunol. 1992. PMID: 1387655 - Tryptophan metabolism in the central nervous system: medical implications.
Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA. Ruddick JP, et al. Expert Rev Mol Med. 2006 Aug 31;8(20):1-27. doi: 10.1017/S1462399406000068. Expert Rev Mol Med. 2006. PMID: 16942634 Review. - Tryptophan metabolites and brain disorders.
Stone TW, Mackay GM, Forrest CM, Clark CJ, Darlington LG. Stone TW, et al. Clin Chem Lab Med. 2003 Jul;41(7):852-9. doi: 10.1515/CCLM.2003.129. Clin Chem Lab Med. 2003. PMID: 12940508 Review.
Cited by
- Tryptophan Breakdown in Patients with HCV Infection is Influenced by IL28B Polymorphism.
Zoller H, Jenal A, Staettermayer AF, Schroecksnadel S, Ferenci P, Fuchs D. Zoller H, et al. Pharmaceuticals (Basel). 2015 Jun 18;8(2):337-50. doi: 10.3390/ph8020337. Pharmaceuticals (Basel). 2015. PMID: 26096654 Free PMC article. - KXS Balances the Tryptophan Metabolism in Mild to Moderate Depressed Patients and Chronic Restraint Stress Induced Depressive Rats.
Wang Y, Li X, Jing R, Yang W, Wang Y, Wang C, Yao L, Cui X, Hu Y. Wang Y, et al. Neuropsychiatr Dis Treat. 2022 Nov 1;18:2485-2496. doi: 10.2147/NDT.S377982. eCollection 2022. Neuropsychiatr Dis Treat. 2022. PMID: 36345420 Free PMC article. - Tat-indoleamine 2,3-dioxygenase 1 elicits neuroprotective effects on ischemic injury.
Park JH, Kim DW, Shin MJ, Park J, Han KH, Lee KW, Park JK, Choi YJ, Yeo HJ, Yeo EJ, Sohn EJ, Kim HC, Shin EJ, Cho SW, Kim DS, Cho YJ, Eum WS, Choi SY. Park JH, et al. BMB Rep. 2020 Nov;53(11):582-587. doi: 10.5483/BMBRep.2020.53.11.114. BMB Rep. 2020. PMID: 32684242 Free PMC article. - SLC6A4 DNA Methylation Levels and Serum Kynurenine/Tryptophan Ratio in Eating Disorders: A Possible Link with Psychopathological Traits?
Franzago M, Orecchini E, Porreca A, Mondanelli G, Orabona C, Dalla Ragione L, Di Nicola M, Stuppia L, Vitacolonna E, Beccari T, Ceccarini MR. Franzago M, et al. Nutrients. 2023 Jan 13;15(2):406. doi: 10.3390/nu15020406. Nutrients. 2023. PMID: 36678277 Free PMC article. - The Plasma [Kynurenine]/[Tryptophan] Ratio and Indoleamine 2,3-Dioxygenase: Time for Appraisal.
Badawy AA, Guillemin G. Badawy AA, et al. Int J Tryptophan Res. 2019 Aug 21;12:1178646919868978. doi: 10.1177/1178646919868978. eCollection 2019. Int J Tryptophan Res. 2019. PMID: 31488951 Free PMC article. Review.
References
- Mcmenamy RH. Binding of indole analogues to human serum albumin. Effects of fatty acids. J Biol Chem. 1965;240:4235–43. - PubMed
- Hargreaves KM, Pardridge WM. Neutral amino acid transport at the human blood-brain barrier. J Biol Chem. 1988;263:19392–7. - PubMed
- Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA. Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med. 2006;8:1–27. - PubMed
- Takikawa O. Biochemical and medical aspects of the indoleamine 2,3-dioxygenase-initiated L-tryptophan metabolism. Biochem Biophys Res Commun. 2005;338:12–9. - PubMed
LinkOut - more resources
Full Text Sources
Other Literature Sources