Leucine and tryptophan metabolism in rats.
Ontology highlight
ABSTRACT:
SUBMITTER: Salter M
PROVIDER: S-EPMC1144587 | biostudies-other | 1985 Jan
REPOSITORIES: biostudies-other
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Project description:The rate of leucine C-2 incorporation into glutamine was compared in control and septic rats. Female Sprague-Dawley rats (n = 46, 210-260 g) were fed parenterally for 3 days and then randomized into two groups (control and septic). Sepsis was induced by the injection of 10(10) live Escherichia coli/kg on day 4 into the septic group. Rats in each group were given a continuous (8 h) infusion of one of three different isotopes. The isotopes were given 24 h after inoculation. Leucine oxidation and incorporation into protein were determined with [1-13C]leucine; glutamine flux and oxidation were determined with [5-13C]glutamine, and the fraction of leucine C-2 incorporated into glutamine was determined by giving [1,2-13C]leucine. Results were as follows: sepsis caused a significant increase in the rate of leucine C-2 incorporation into glutamine (66.0 +/- 3.7 as against 29.6 +/- 3.7 mumol/h per kg, P less than 0.01). This increase was due to both an increase in glutamine production (2331 +/- 76 as against 1959 +/- 94 mumol/h per kg, P less than 0.01) and an increase in the proportion of glutamine derived from leucine (2.83 +/- 0.27% as against 1.51 +/- 0.31%, P less than 0.01). The ratio of leucine C-2 incorporated into glutamine to leucine oxidized increased from 7.16 +/- 0.91% to 11.49 +/- 1.12% with sepsis (P less than 0.05).
| S-EPMC1151106 | biostudies-other
Project description:1. Protein-calorie-depleted rats exhibit a decreased ability to oxidize leucine as compared with control animals. 2. The block in degradation of l-leucine is due to decreased activities of l-leucine transaminase and d-amino acid oxidase associated with liver mitochondria. 3. Cytoplasmic l-leucine transaminase in liver is not affected by the protein depletion. 4. The specific activities of the mitochondrial enzymes can be increased by a single oral dose of 1g. of Bacto-Peptone (meat hydrolysate). The effect of Bacto-Peptone can be inhibited by prior administration of dosages of 10mg. of puromycin/100g. body wt., suggesting that the increased enzyme specific activities may be due to new synthesis of enzyme protein.
| S-EPMC1187577 | biostudies-other
Project description:Tiansi Liquid is a traditional Chinese herbal medicine used to treat depression; however, the underlying mechanisms remain unclear. Here, we examined the effect of Tiansi Liquid in a rat model of hydrocortisone-induced depression using behavioral testing, 16S rRNA high-throughput pyrosequencing and high-performance liquid chromatography-mass spectrometry-based metabolomics of the tryptophan (TRP)?kynurenine (KYN) pathway. Tiansi Liquid significantly improved the sucrose preference and exploratory behavior of the depressive rats. The richness of intestinal mucosa samples from the model (depressive) group tended to be higher than that from the control group, while the richness was higher in the Tiansi Liquid-treated group than in the model group. Tiansi Liquid increased the relative abundance of some microbiota (Ruminococcaceae, Lactococcus, Lactobacillus, Lachnospiraceae_NK4A136_group). Metabolomics showed that Tiansi Liquid reduced the levels of tryptophan 2,3 dioxygenase, indoleamine 2,3-dioxygenase, quinoline and the KYN/TRP ratio, while increasing kynurenic acid and 5-HT levels. Correlation analysis revealed a negative relationship between the relative abundance of the Lachnospiraceae_NK4A136_group and quinoline content. Collectively, these findings suggest that Tiansi Liquid ameliorates depressive symptoms in rats by modulating the gut microbiota composition and metabolites in the TRP?KYN pathway.
| S-EPMC6278342 | biostudies-literature
Project description:BACKGROUND:Amino acids have been reported to act as modulators of various regulatory processes and to provide new therapeutic applications for either the prevention or treatment of metabolic disorders. The purpose of the present study is to investigate the effects of single oral dose administration and a continuous treatment of L-tryptophan (L-Trp) on the regulation of blood pressure and glucose metabolism in stroke-prone spontaneously hypertensive rats (SHRSP). METHODS:First, male 9-week-old SHRSP were administered 100 mg L-Trp·kg-1 body weight in saline to the L-Trp group and 0.9% saline to the control group via a gastric tube as a single oral dose of L-Trp. Second, three groups of SHRSP were fed an AIN-93M-based diet supplemented with L-tryptophan (L-Trp) (0, 200, or 1000 mg·kg-1 diet) for 3 weeks as continuous treatment of L-Trp. RESULTS:Single oral dose administration of L-Trp improved blood pressure, blood glucose, and insulin levels. Blood pressure, blood glucose, and insulin levels improved significantly in the L-Trp treatment groups. The administration of L-Trp also significantly increased plasma nitric oxide and serotonin levels. CONCLUSION:L-Trp by both single oral dose administration and continuous treatment improves glucose metabolism and blood pressure in SHRSP.
| S-EPMC3152873 | biostudies-literature
Project description:Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degradation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Additionally, tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurologic and psychiatric disorders. Gut microbes influence tryptophan metabolism directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurologic and psychiatric disorders where tryptophan and its metabolites play a prominent role. In this review, we will touch upon some of these features and their involvement in health and disease.
| S-EPMC8000752 | biostudies-literature
Project description:In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive, and psychiatric symptoms of depression commonly observed after myocardial infarction. Peripheral 5-hydroxytryptamine is an important substance in the gut-brain axis, and its abnormal metabolism is a critical finding after myocardial infarct.
| S-EPMC5315315 | biostudies-literature
Project description:DNA microarray analysis of gene expression in response to physiological and genetic changes that affect tryptophan metabolism in Escherichia coli. We investigated the global changes in mRNA abundance in Escherichia coli elicited by various perturbations of tryptophan metabolism. To do so we printed DNA microarrays containing 95% of all annotated E. coli ORFs. We determined the expression profile that is predominantly dictated by the activity of the tryptophan repressor. Only three operons, trp, mtr, and aroH, exhibited appreciable expression changes consistent with this profile. The quantitative changes we observed in mRNA levels for the five genes of the trp operon were consistent within a factor of 2, with expectations based on established Trp protein levels. Several operons known to be regulated by the TyrR protein, aroF-tyrA, aroL, aroP, and aroG, were down-regulated on addition of tryptophan. TyrR can be activated by any one of the three aromatic amino acids. Only one operon, tnaAB, was significantly activated by the presence of tryptophan in the medium. We uncovered a plethora of likely indirect effects of changes in tryptophan metabolism on intracellular mRNA pools, most prominent of which was the sensitivity of arginine biosynthetic operons to tryptophan starvation. This study is detailed in Khodursky AB et al.(2000) Proc Natl Acad Sci U S A 97:12170-5 Keywords: other
2001-07-30 | GSE7 | GEO
Project description:Crosstalk between the gut microbiome and the host plays an important role in animal development and health. Small compounds are key mediators in this host-gut microbiome dialogue. For instance, tryptophan metabolites, generated by biotransformation of tryptophan through complex host-microbiome co-metabolism can trigger immune, metabolic, and neuronal effects at local and distant sites. However, the origin of tryptophan metabolites and the underlying tryptophan metabolic pathway(s) are not well characterized in the current literature. A large number of the microbial contributors of tryptophan metabolism remain unknown, and there is a growing interest in predicting tryptophan metabolites for a given microbiome. Here, we introduce TrpNet, a comprehensive database and analytics platform dedicated to tryptophan metabolism within the context of host (human and mouse) and gut microbiome interactions. TrpNet contains data on tryptophan metabolism involving 130 reactions, 108 metabolites and 91 enzymes across 1246 human gut bacterial species and 88 mouse gut bacterial species. Users can browse, search, and highlight the tryptophan metabolic pathway, as well as predict tryptophan metabolites on the basis of a given taxonomy profile using a Bayesian logistic regression model. We validated our approach using two gut microbiome metabolomics studies and demonstrated that TrpNet was able to better predict alterations in in indole derivatives compared to other established methods.
| S-EPMC8777792 | biostudies-literature
Project description:1. The metabolism of L-tryptophan by liver cells prepared from fed normal, adrenalectomized and streptozotocin-diabetic rats was studied. 2. At physiological concentrations (0.1 mM), the rate of oxidation of tryptophan by tryptophan 2,3-dioxygenase was 3-fold greater in liver cells from diabetic rats than in those from fed rats. In liver cells from diabetic rats, oxidation of tryptophan to CO2 and metabolites of the glutarate pathway was increased 7-fold. Quinolinate synthesis was decreased by 50%. These findings are consistent with an increase in picolinate carboxylase activity. 3. Rates of metabolism of 0.1 mM-tryptophan by hepatocytes from fed and adrenalectomized rats were similar. 4. In all three types of cell preparation, fluxes through tryptophan 2,3-dioxygenase with 2.5 mM-tryptophan were 7-fold greater than those obtained with 0.1 mM-tryptophan. Tryptophan 2,3-dioxygenase and kynureninase fluxes in hepatocytes from fed and adrenalectomized rats were comparable, whereas those in liver cells from diabetic rats were increased 2.5-fold and 3.3-fold respectively. Picolinate carboxylase activities of liver cells from diabetic rats were 15-fold greater than those of cells from fed rats, but rates of quinolinate synthesis were unchanged. 5. It is concluded that: (i) adrenal corticosteroids are not required for the maintenance of basal activities of the kynurenine pathway, whereas (ii) chronic insulin deficiency produces changes in both the rate of oxidation and metabolic fate of tryptophan carbon.
| S-EPMC1163583 | biostudies-other
Project description:Following therapy, tumour-initiating cells (TICs) survive and give rise to second-line tumours. Gene set enrichment analysis of microarray data and microRNA analysis confirmed the validity of spheroid cultures as models of TICs for breast and prostate cancer and mesothelioma cell lines. Pathway analysis revealed increased Trp metabolism in all types of TICs with indoleamine 2,3-dioxygenase (IDO) as the rate-limiting enzyme. TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. Mitocans, represented by vitamin E (VE) analogues, suppressed IDO1 in TICs with functional mitochondrial complex II, a target for the agents. IDO1 expression was regulated via a mechanism involving both transcriptional and post-transcriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work points to Trp metabolism as a novel mechanism of TICs to bypass the immune surveillance and to VE analogues as agents that remove this ‘mimicry’. Total RNA obtained from from breast cancer (MCF7), mesothelioma (IstMes2) and prostate cancer (LNCaP) adherent cell lines was compared to their corresponding sphere cultures
2013-11-01 | E-GEOD-41980 | biostudies-arrayexpress