International Journal of Tryptophan Research最新文献

{"title":"Assessment of the Human Kynurenine Pathway: Comparisons and Clinical Implications of Ethnic and Gender Differences in Plasma Tryptophan, Kynurenine Metabolites, and Enzyme Expressions at Baseline and After Acute Tryptophan Loading and Depletion.","authors":"Abdulla A-B Badawy,&nbsp;Donald M Dougherty","doi":"10.4137/IJTR.S38189","DOIUrl":"https://doi.org/10.4137/IJTR.S38189","url":null,"abstract":"<p><p>Tryptophan (Trp) metabolism via the kynurenine pathway (KP) was assessed in normal healthy US volunteers at baseline and after acute Trp depletion (ATD) and acute Trp loading (ATL) using amino acid formulations. The hepatic KP accounts for ~90% of overall Trp degradation. Liver Trp 2,3-dioxygenase (TDO) contributes ~70% toward Trp oxidation, with the remainder achieved by subsequent rate-limiting enzymes in the KP. TDO is not influenced by a 1.15 g Trp load, but is maximally activated by a 5.15 g dose. We recommend a 30 mg/kg dose for future ATL studies. ATD activates TDO and enhances the Trp flux down the KP via its leucine component. Higher plasma free [Trp] and lower total [Trp] are observed in women, with no gender differences in kynurenines. Kynurenic acid is lower in female Caucasians, which may explain their lower incidence of schizophrenia. African-American and Hispanic women have a lower TDO and Trp oxidation relative to free Trp than the corresponding men. African-American women have a potentially higher 3-hydroxyanthranilic acid/anthranilic acid ratio, which may protect them against osteoporosis. Future studies of the KP in relation to health and disease should focus on gender and ethnic differences. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"9 ","pages":"31-49"},"PeriodicalIF":4.4,"publicationDate":"2016-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S38189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34324501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria.","authors":"Halina Baran,&nbsp;Katrin Staniek,&nbsp;Melanie Bertignol-Spörr,&nbsp;Martin Attam,&nbsp;Carina Kronsteiner,&nbsp;Berthold Kepplinger","doi":"10.4137/IJTR.S37973","DOIUrl":"https://doi.org/10.4137/IJTR.S37973","url":null,"abstract":"<p><p>Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3), respiratory control index (RC) and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM) or succinate (10 mM) and in the presence of L-tryptophan metabolites (1 mM) or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver and heart mitochondria. Alterations of L-tryptophan metabolism might have an impact on the bioenergetic activities of brain, liver and/or heart mitochondria and might be involved in the development of clinical symptoms such as cardiomyopathy, hepatopathy and dementia. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"9 ","pages":"17-29"},"PeriodicalIF":4.4,"publicationDate":"2016-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S37973","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34427205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diet Versus Exercise in Weight Loss and Maintenance: Focus on Tryptophan.","authors":"Barbara Strasser,&nbsp;Dietmar Fuchs","doi":"10.4137/IJTR.S33385","DOIUrl":"https://doi.org/10.4137/IJTR.S33385","url":null,"abstract":"<p><p>An association between mood disturbance, the inability to lose or to stop gaining weight, and a craving for carbohydrates is manifested by many people who are overweight or are becoming so. In a recent study, we observed that low-calorie weight loss diet lowered not only levels of leptin but also levels of essential amino acid tryptophan (TRP) significantly. The disturbed metabolism of TRP might affect biosynthesis of serotonin and could thereby increase the susceptibility for mood disturbances and carbohydrate craving, increasing the cessation probability of weight reduction programs. Alternatively, moderate physical exercise - a potent stimulus to modulate (reduce/normalize) proinflammatory cytokines, which may affect TRP levels - could be helpful in improving mood status and preventing uncontrolled weight gain. In contrast, excessive physical exercise may induce breakdown of TRP when proinflammatory cascades together with TRP-degrading enzyme indoleamine 2,3-dioxygenase-1 are stimulated, which may lead to neuropsychiatric symptoms such as fatigue and low mood. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"9 ","pages":"9-16"},"PeriodicalIF":4.4,"publicationDate":"2016-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S33385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34564411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organ Correlation with Tryptophan Metabolism Obtained by Analyses of TDO-KO and QPRT-KO Mice.","authors":"Katsumi Shibata,&nbsp;Tsutomu Fukuwatari","doi":"10.4137/IJTR.S37984","DOIUrl":"https://doi.org/10.4137/IJTR.S37984","url":null,"abstract":"<p><p>The aim of this article is to report the organ-specific correlation with tryptophan (Trp) metabolism obtained by analyses of tryptophan 2,3-dioxygenase knockout (TDO-KO) and quinolinic acid phosphoribosyltransferase knockout (QPRT-KO) mice models. We found that TDO-KO mice could biosynthesize the necessary amount of nicotinamide (Nam) from Trp, resulting in the production of key intermediate, 3-hydroxyanthranilic acid. Upstream metabolites, such as kynurenic acid and xanthurenic acid, in the urine were originated from nonhepatic tissues, and not from the liver. In QPRT-KO mice, the Trp to quinolinic acid conversion ratio was 6%; this value was higher than expected. Furthermore, we found that QPRT activity in hetero mice was half of that in wild-type (WT) mice. Urine quinolinic acid levels remain unchanged in both hetero and WT mice, and the conversion ratio of Trp to Nam was also unaffected. Collectively, these findings show that QPRT was not the rate-limiting enzyme in the conversion. In conclusion, the limiting factors in the conversion of Trp to Nam are the substrate amounts of 3-hydroxyanthranilic acid and activity of 3-hydroxyanthranilic acid 3,4-dioxygenase in the liver. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"9 ","pages":"1-7"},"PeriodicalIF":4.4,"publicationDate":"2016-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S37984","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34521203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment Among HIV-infected Individuals","authors":"Michael R. Keegan, S. Chittiprol, S. Letendre, A. Winston, D. Fuchs, A. Boasso, J. Iudicello, R. Ellis","doi":"10.4137/IJTR.S36464","DOIUrl":"https://doi.org/10.4137/IJTR.S36464","url":null,"abstract":"Objective Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals. Methods In a cross-sectional analysis, concentrations of neopterin (NEO), tumor necrosis factor-alpha, TRP, KYN, KYN/TRP ratio, phenylalanine (PHE), tyrosine (TYR), PHE/TYR ratio, and nitrite were assessed in the cerebrospinal fluid (CSF) and plasma of HIV+(n = 91) and HIV-negative (HIV-) individuals (n = 66). CI and MDD were assessed via a comprehensive neuropsychological test battery. A Global Deficit Score ≥0.5 was defined as CI. Nonparametric statistical analyses included Kruskal–Wallis and Mann–Whitney U tests, and multivariate logistic regression. Results Following Bonferroni correction, NEO concentrations were found to be greater in CSF and TRP concentration was found to be lower in the plasma of HIV+ versus HIV– individuals, including a subgroup of aviremic (defined as HIV-1 RNA <50 cps/mL) HIV+ participants receiving antiretroviral therapy (n = 44). There was a nonsignificant trend toward higher KYN/TRP ratios in plasma in the HIV+ group (P = 0.027; Bonferroni corrected α = 0.0027). In a logistic regression model, lower KYN/TRP ratios in plasma were associated with CI and MDD in the overall HIV+ group (P = 0.038 and P = 0.063, respectively) and the aviremic subgroup (P = 0.066 and P = 0.027, respectively), though this observation was not statistically significant following Bonferroni correction (Bonferroni corrected α = 0.0031). Conclusions We observed a trend toward lower KYN/TRP ratios in aviremic HIV+ patients with CI and MDD.","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"65 1","pages":"79 - 88"},"PeriodicalIF":4.4,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76874550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Kynurenine Pathway Is a Double-Edged Sword in Immune-Privileged Sites and in Cancer: Implications for Immunotherapy","authors":"J. Routy, B. Routy, Gina M. Graziani, V. Mehraj","doi":"10.4137/IJTR.S38355","DOIUrl":"https://doi.org/10.4137/IJTR.S38355","url":null,"abstract":"The term “immune privilege” was originally coined to describe the suppression of inflammatory responses within organs protected by anatomic barriers, ie, the eyes, brain, placenta, and testes. However, cellular and metabolic processes, which orchestrate immune responses, also control inflammation within these sites. Our current understanding of tolerogenic mechanisms has extended the definition of immune privilege to include hair follicles, the colon, and cancer. By catabolizing tryptophan, cells expressing the enzyme indoleamine-2,3-dioxygenase produce kynurenine metabolites, which orchestrate local and systemic responses to control inflammation, thus maintaining immune privilege. This review highlights the double-edged role played by the kynurenine pathway (KP), which establishes and maintains immune-privileged sites while contributing to cancer immune escape. The identification of the underlying molecular drivers of the KP in immune-privileged sites and in cancer is essential for the development of novel therapies to treat autoimmunity and cancer and to improve transplantation outcomes.","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"13 1","pages":"67 - 77"},"PeriodicalIF":4.4,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74231724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Antipsychotic Treatment in the Rat - Effects on Brain Interleukin-8 and Kynurenic Acid.","authors":"Markus K Larsson,&nbsp;Lilly Schwieler,&nbsp;Michel Goiny,&nbsp;Sophie Erhardt,&nbsp;Göran Engberg","doi":"10.4137/IJTR.S25915","DOIUrl":"https://doi.org/10.4137/IJTR.S25915","url":null,"abstract":"<p><p>Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA) and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6), olanzapine (2 mg/kg, n = 6), and clozapine (20 mg/kg, n = 6) or saline (n = 6) for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF) levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"8 ","pages":"49-52"},"PeriodicalIF":4.4,"publicationDate":"2015-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S25915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34138875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests.","authors":"Vikram Mehraj,&nbsp;Jean-Pierre Routy","doi":"10.4137/IJTR.S26862","DOIUrl":"https://doi.org/10.4137/IJTR.S26862","url":null,"abstract":"<p><p>l-Tryptophan (l-Trp) is an essential amino acid that possesses diverse metabolic, neurological, and immunological roles spanning from the synthesis of proteins, neurotransmitter serotonin, and neurohormone melatonin, to its degradation into immunosuppressive catabolites by indoleamine-2, 3-dioxygenase (IDO) in the kynurenine pathway (KP). Trp catabolites, by activating aryl hydrocarbon receptor (AhR), play an important role in antimicrobial defense and immune regulation. IDO/AhR acts as a double-edged sword by both depleting l-Trp to starve the invaders and by contributing to the state of immunosuppression with microorganisms that were not cleared during acute infection. Pathogens experiencing Trp deprivation by IDO-mediated degradation include certain bacteria, parasites, and less likely viruses. However, chronic viral infections highjack the host immune response to create a state of disease tolerance via kynurenine catabolites. This review covers the latest data involving chronic viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes, and cytomegalovirus (CMV) and their cellular interplay with Trp catabolites. Strategies developed by viruses to escape immune control also represent new avenues for therapeutic interventions based on Trp metabolism. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"8 ","pages":"41-8"},"PeriodicalIF":4.4,"publicationDate":"2015-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S26862","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33950932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Method for Evaluation of the Requirements of B-group Vitamins Using Tryptophan Metabolites in Human Urine.","authors":"Katsumi Shibata, Junko Hirose, Tsutomu Fukuwatari","doi":"10.4137/IJTR.S24412","DOIUrl":"10.4137/IJTR.S24412","url":null,"abstract":"<p><p>Tryptophan metabolism is directly involved with B-group vitamins such as vitamin B2, niacin, and vitamin B6, and indirectly with vitamin B1 and pantothenic acid. We evaluated the validity of requirements of B-group vitamins set by the Dietary Reference Intakes for the Japanese (DRI-J). We investigated the fate of dietary tryptophan in 10 Japanese adult men who ate the same diet based on DRI-J during a 4-week study. Vitamin mixtures were administered based on the amounts in the basal diet during weeks 2, 3, and 4. Daily urine samples were collected eight times (days 1 and 5 in each week). Administration of vitamin mixtures had no effect on tryptophan metabolites such as anthranilic acid, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, and quinolinic acid within individuals. Surplus administration of B-group vitamins against DRI-J requirements did not elicit beneficial effects on tryptophan metabolism. Our findings supported the requirements of B-group vitamins set by the DRI-J. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"8 ","pages":"31-9"},"PeriodicalIF":4.4,"publicationDate":"2015-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33314114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tryptophan-ethylester, the false (unveiled) melatonin isomer in red wine.","authors":"Marcello Iriti,&nbsp;Ileana Vigentini","doi":"10.4137/IJTR.S22450","DOIUrl":"https://doi.org/10.4137/IJTR.S22450","url":null,"abstract":"<p><p>Among the food plants, the presence of melatonin in grapes (Vitis vinifera L.) deserves particular attention because of the production of wine, an alcoholic beverage of economic relevance and with putative healthy effects. Furthermore, melatonin isomers have been detected in wine too. Recently, one of these isomers has been identified as tryptophan-ethylester, a compound with the same molecular weight of melatonin. In this Commentary, we briefly comment the source(s) of tryptophan-ethylester in wine and the putative nutritional role(s). </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"8 ","pages":"27-9"},"PeriodicalIF":4.4,"publicationDate":"2015-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S22450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33139871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}