International Journal of Tryptophan Research最新文献

{"title":"The Influence of Nicotinamide on Health and Disease in the Central Nervous System.","authors":"Rosemary A Fricker, Emma L Green, Stuart I Jenkins, Síle M Griffin","doi":"10.1177/1178646918776658","DOIUrl":"10.1177/1178646918776658","url":null,"abstract":"<p><p>Nicotinamide, the amide form of vitamin B₃ (niacin), has long been associated with neuronal development, survival, and function in the central nervous system (CNS), being implicated in both neuronal death and neuroprotection. Here, we summarise a body of research investigating the role of nicotinamide in neuronal health within the CNS, with a focus on studies that have shown a neuroprotective effect. Nicotinamide appears to play a role in protecting neurons from traumatic injury, ischaemia, and stroke, as well as being implicated in 3 key neurodegenerative conditions: Alzheimer's, Parkinson's, and Huntington's diseases. A key factor is the bioavailability of nicotinamide, with low concentrations leading to neurological deficits and dementia and high levels potentially causing neurotoxicity. Finally, nicotinamide's potential mechanisms of action are discussed, including the general maintenance of cellular energy levels and the more specific inhibition of molecules such as the nicotinamide adenine dinucleotide-dependent deacetylase, sirtuin 1 (SIRT1).</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646918776658"},"PeriodicalIF":2.7,"publicationDate":"2018-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/71/fb/10.1177_1178646918776658.PMC5966847.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36173866","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":"Reexamining IFN-γ Stimulation of De Novo NAD+ in Monocyte-Derived Macrophages.","authors":"Peter Moon,&nbsp;Paras Singh Minhas","doi":"10.1177/1178646918773067","DOIUrl":"https://doi.org/10.1177/1178646918773067","url":null,"abstract":"4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). https://doi.org/10.1177/1178646918773067 International Journal of Tryptophan Research Volume 11: 1 © The Author(s) 2018 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1 78646918773067","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646918773067"},"PeriodicalIF":4.4,"publicationDate":"2018-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646918773067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36127648","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":"Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents.","authors":"Abdulla A-B Badawy","doi":"10.1177/1178646917753422","DOIUrl":"https://doi.org/10.1177/1178646917753422","url":null,"abstract":"<p><p>Modulation of tryptophan (Trp) metabolism may underpin the behavioral effects of androgenic-anabolic steroids (AAS) and associated image and performance enhancers. Euphoria, arousal, and decreased anxiety observed with moderate use and exercise may involve enhanced cerebral serotonin synthesis and function by increased release of albumin-bound Trp and estrogen-mediated liver Trp 2,3-dioxygenase (TDO) inhibition and enhancement of serotonin function. Aggression, anxiety, depression, personality disorders, and psychosis, observed on withdrawal of AAS or with use of large doses, can be caused by decreased serotonin synthesis due to TDO induction on withdrawal, excess Trp inhibiting the 2 enzymes of serotonin synthesis, and increased cerebral levels of neuroactive kynurenines. Exercise and excessive protein and branched-chain amino acid intakes may aggravate the effects of large AAS dosage. The hypothesis is testable in humans and experimental animals by measuring parameters of Trp metabolism and disposition and related metabolic processes.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646917753422"},"PeriodicalIF":4.4,"publicationDate":"2018-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917753422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35868471","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":"Indoleamine 2,3-Dioxygenase Activity Increases NAD+ Production in IFN-γ-Stimulated Human Primary Mononuclear Cells.","authors":"Ross S Grant","doi":"10.1177/1178646917751636","DOIUrl":"https://doi.org/10.1177/1178646917751636","url":null,"abstract":"<p><p>IFN-γ activation of mononuclear phagocytes significantly increases indoleamine 2,3-dioxygenase (IDO) and flux through the kynurenine pathway (KP). However, the effect of IDO on NAD+ synthesis, the end product of KP metabolism, is unknown. To investigate this, primary human peripheral blood mononuclear cells were cultured up to 10 days and activated with IFN-γ in the presence or absence of a poly(ADP-ribose) polymerase (PARP) inhibitor. Day 10 macrophages had significantly higher NAD+ levels compared with monocytes. IFN-γ activation of macrophages resulted in the highest induction of IDO but decreased intracellular NAD+ concentrations at both 24 and 48 hours. However, IFN-γ activation of both day 6 and day 10 macrophages in the presence of a PARP inhibitor resulted in significantly higher intracellular NAD+ levels at 24 hours. This study provides evidence for the first time that an immune-mediated increase in IDO activity increases NAD+ biosynthesis concomitantly with an increase in NAD+ catabolism in primary human macrophages.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646917751636"},"PeriodicalIF":4.4,"publicationDate":"2018-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917751636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35745001","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 in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers.","authors":"Subrata Debnath,&nbsp;Chakradhar Velagapudi,&nbsp;Laney Redus,&nbsp;Farook Thameem,&nbsp;Balakuntalam Kasinath,&nbsp;Claudia E Hura,&nbsp;Carlos Lorenzo,&nbsp;Hanna E Abboud,&nbsp;Jason C O'Connor","doi":"10.1177/1178646917694600","DOIUrl":"https://doi.org/10.1177/1178646917694600","url":null,"abstract":"<p><strong>Objective: </strong>Type 2 diabetes (T2D) is the primary case of chronic kidney disease (CKD). Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP) metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD.</p><p><strong>Methods: </strong>Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis. Key TRP metabolites (kynurenine [KYN], kynurenic acid [KYNA], and quinolinic acid [QA]), proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]), and C-reactive protein were measured in plasma. The KYN/TRP ratio was utilized as a surrogate marker for indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity.</p><p><strong>Results: </strong>There was a significant inverse association between circulating TRP level and stages of CKD (<i>P</i>< 0.0001). Downstream bioactive TRP metabolites KYN, KYNA, and QA were positively and robustly correlated with the severity of kidney disease (<i>P</i> < 0.0001). In multiple linear regression, neither TNF-α nor IL-6 was independently related to KYN/TRP ratio after adjusting for estimated glomerular filtration rate (eGFR). Only TNF-α was independently related to KYN after taking into account the effect of eGFR.</p><p><strong>Conclusions: </strong>Chronic kidney disease secondary to T2D may be associated with accumulation of toxic TRP metabolites due to both inflammation and impaired kidney function. Future longitudinal studies to determine whether the accumulation of KYN directly contributes to CKD progression and associated symptoms in patients with T2D are warranted.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"10 ","pages":"1178646917694600"},"PeriodicalIF":4.4,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917694600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9546380","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 in Rat Liver After Administration of Tryptophan, Kynurenine Metabolites, and Kynureninase Inhibitors.","authors":"Abdulla A-B Badawy,&nbsp;Samina Bano","doi":"10.4137/IJTR.S38190","DOIUrl":"https://doi.org/10.4137/IJTR.S38190","url":null,"abstract":"<p><p>Rat liver tryptophan (Trp), kynurenine pathway metabolites, and enzymes deduced from product/substrate ratios were assessed following acute and/or chronic administration of kynurenic acid (KA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), Trp, and the kynureni-nase inhibitors benserazide (BSZ) and carbidopa (CBD). KA activated Trp 2,3-dioxygenase (TDO), possibly by increasing liver 3-HAA, but inhibited kynurenine aminotransferase (KAT) and kynureninase activities with 3-HK as substrate. 3-HK inhibited kynureninase activity from 3-HK. 3-HAA stimulated TDO, but inhibited kynureninase activity from K and 3-HK. Trp (50 mg/kg) increased kynurenine metabolite concentrations and KAT from K, and exerted a temporary stimulation of TDO. The kynureninase inhibitors BSZ and CBD also inhibited KAT, but stimulated TDO. BSZ abolished or strongly inhibited the Trp-induced increases in liver Trp and kynurenine metabolites. The potential effects of these changes in conditions of immune activation, schizophrenia, and other disease states are discussed. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"9 ","pages":"51-65"},"PeriodicalIF":4.4,"publicationDate":"2016-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S38190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34324502","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":"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}