GNPS Amino Acid Conjugate Bile Acids
Ontology highlight
ABSTRACT:
INSTRUMENT(S): maXis
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Pieter Dorrestein
PROVIDER: MSV000082467 | GNPS | Wed Jun 13 11:32:00 BST 2018
REPOSITORIES: GNPS
Similar Datasets
Project description:Objective: Insulin regulates amino acid metabolism. We investigated whether glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes affect amino acid levels in a large population-based cohort. Subjects and Methods: A total of 9,371 non-diabetic or newly-diagnosed type 2 diabetic Finnish men from the population-based METSIM Study were studied. Proton NMR spectroscopy was used to measure plasma levels of 8 amino acids. Genotyping of 42 SNPs and mRNA microarray analysis from 200 subcutaneous adipose tissue samples were performed. Results: Increasing fasting and/or 2-hour plasma glucose levels were associated with increasing levels of alanine, valine, leucine, isoleucine, phenylalanine and tyrosine, and decreasing levels of histidine and glutamine. We also found significant correlations between insulin sensitivity (Matsuda ISI) and expression of genes regulating amino acid metabolism. Only one SNP (rs780094 in GCKR) of the 42 risk SNPs for type 2 diabetes or hyperglycemia was significantly associated with the levels of alanine, isoleucine, and glutamine. Conclusions : We observed that the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia. These associations seemed to be mediated by insulin resistance, at least in part. GCKR rs780094 was significantly associated with several amino acids. Total RNA was obtained from subcutaneous fat biopsies from 200 people participating in the METSIM study (4 samples were replicated for a total of 204 arrays).
2012-04-01 | E-GEOD-32512 | biostudies-arrayexpress
Project description:Objective: Insulin regulates amino acid metabolism. We investigated whether glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes affect amino acid levels in a large population-based cohort. Subjects and Methods: A total of 9,371 non-diabetic or newly-diagnosed type 2 diabetic Finnish men from the population-based METSIM Study were studied. Proton NMR spectroscopy was used to measure plasma levels of 8 amino acids. Genotyping of 42 SNPs and mRNA microarray analysis from 200 subcutaneous adipose tissue samples were performed. Results: Increasing fasting and/or 2-hour plasma glucose levels were associated with increasing levels of alanine, valine, leucine, isoleucine, phenylalanine and tyrosine, and decreasing levels of histidine and glutamine. We also found significant correlations between insulin sensitivity (Matsuda ISI) and expression of genes regulating amino acid metabolism. Only one SNP (rs780094 in GCKR) of the 42 risk SNPs for type 2 diabetes or hyperglycemia was significantly associated with the levels of alanine, isoleucine, and glutamine. Conclusions : We observed that the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia. These associations seemed to be mediated by insulin resistance, at least in part. GCKR rs780094 was significantly associated with several amino acids.
2012-04-02 | GSE32512 | GEO
Project description:Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR.
2016-02-04 | GSE77529 | GEO
Project description:Bile acids are not only crucial for the uptake of lipids, but also have widespread systematic ef-fects and shape the gut-microbiome composition. Bile acids can directly shape the gut-microbiome and can be modified by bacteria such as Eggerthella lenta which in turn plays a crucial role in host metabolism and immune response. We cultivated eight strains that represent a simplified human intestinal microbiome and inves-tigated the molecular response to bile acids, co-culturing with Eggerthella lenta and the combina-tion. We observed growth inhibition of particularly gram-positive strains during bile acid stress, which could be alleviated through co-culturing with Eggerthella lenta. The inhibition of growth was related to a decrease in membrane integrity and genotoxic effects of bile acids, which we investigated using zeta potential measurements in combination with proteomic and metabolomic analyses. Co-culturing with Eggerthella lenta alleviated stress through formation of oxidized and epimer-ized bile acids and the molecular response to co-culturing was seen to be strain specific. We also note that we could detect the recently described Microbial Bile Salt Conjugates in our cultures. This study highlights the significance of a potent bile acid modifier and how in-depth molecular analyses are required to decipher cross-communication between gut and host.
2023-02-24 | PXD035496 | Pride
Project description:Bile acids are important signaling molecules with impact on host health and metabolism. However, the diversity of bile acids furnished by both the host and microbes is incompletely characterized. To address this knowledge gap, we created a reusable resource of candidate tandem mass spectrometry (MS/MS) spectra by filtering approximately 1.2 billion publicly available MS/MS spectra from 2,706 untargeted metabolomics projects for bile acid-specific MS/MS ion patterns. Provided here are two MGFs/mzMLs consisting of 594,431 MS/MS spectra directly obtained from the public data on GNPS/MassIVE using MassQL queries designed for non-, mono-, di-, tri-, tetra- and penta-hydroxylated bile acids and MS/MS spectra from synthetic standards of 38 amino acids and 28 polyamines conjugated to bile acids.
2023-04-25 | MSV000091795 | MassIVE
Project description:<p>Gut microbes have been recognized to convert the human bile acids by deconjugation, dehydroxylation, dehydrogenation and epimerization of the cholesterol core, but the ability to re-conjugate them with amino acids as an additional conversion has only been recently described. These new bile acids are known as microbially conjugated bile acids (MCBAs). The aim of this study was evaluating the MCBAs diversity produced by the gut microbiota through a metabolomics approach. In this study, fresh fecal samples from healthy donors were evaluated to explore the re-conjugation of chenodeoxycholic and 3-oxo-chenodeoxycholic acids by the human gut microbiota. No significant differences were found between the conversion trend of both BAs incubations. The <em>in vitro</em> results showed a clear trend to first accumulate the epimer isoursochenodeoxycholic acid, and the dehydroxylated lithocholic acid derivatives in samples incubated with chenodeoxycholic and 3-oxo-chenodeoxycholic acid. Also showed a strong trend for the production of microbially conjugated dehydroxylated bile acids, instead of chenodeoxycholic backbone conjugates. Different molecules and isomers of microbial conjugates with valine and leucine were also identified and confirmed by MS/MS. These results document the gut microbiota capability to produce esters of MCBAs on hydroxyls of the sterol backbone in addition to amides at the C24 acyl site. This study opens a new perspective to study the BAs diversity produced by the human gut microbiota.</p>
2024-01-16 | MTBLS4140 | MetaboLights
Project description:Positive LC-MS/MS data collected for synthetic mixtures of conjugated bile acids made by combining CA, CDCA, DCA, HDCA, UDCA, aMCA, bMCA, or gMCA with 22 different amino acids using ethyl chloroformate, triethylamine, and NaHCO3 or NaOH.
2021-05-26 | MSV000087523 | GNPS
Project description:Positive and negative LC-MS/MS data collected for synthetic mixtures of conjugated bile acids made by combining CA, CDCA, DCA, HDCA, UDCA, aMCA, bMCA, or gMCA with 22 different amino acids using ethyl chloroformate, triethylamine, and NaHCO3 or NaOH.
2021-05-26 | MSV000087522 | GNPS
Project description:This SuperSeries is composed of the SubSeries listed below. CD4+ T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4+ T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn?s disease-like ileitis following transfer into Rag1-/- hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1-/- mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn?s disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis.
2020-01-10 | GSE143405 | GEO
Project description:Its characteristic rose-like aroma makes phenylethanol a popular ingredient in foods, beverages and cosmetics. Microbial production of phenylethanol currently relies on whole-cell bioconversion of phenylalanine with yeasts that harbor an Ehrlich pathway for phenylalanine catabolism. Complete biosynthesis of phenylethanol from a cheap carbon source such as glucose provides an economically attractive alternative for phenylalanine bioconversion. In this study, a Synthetic Genetic Array screening was applied to identify genes involved in regulation of phenylethanol synthesis in Saccharomyces cerevisiae. The screen focused on transcriptional regulation of ARO10, which encodes the major decarboxylase involved in conversion of phenylpyruvate to phenylethanol. A deletion in ARO8, which encodes an aromatic amino acid transaminase, was found to cause a transcriptional upregulation of ARO10 during growth with ammonium sulfate as the sole nitrogen source. Physiological characterization revealed that the aro8 mutation led to substantial changes in the absolute and relative intracellular concentrations of amino acids. Moreover, deletion of ARO8 led to de novo production of phenylethanol during growth on a glucose synthetic medium with ammonium as the sole nitrogen source. The aro8 mutation also stimulated phenylethanol production when combined with other, previously documented mutations that deregulate aromatic amino acid biosynthesis in S. cerevisiae. The resulting engineered S. cerevisiae strain produced over 3 mM of phenylethanol from glucose during growth on a simple synthetic medium. The strong impact of a transaminase deletion on intracellular amino acid concentrations opens new possibilities for yeast-based production of amino acid-derived products.
2014-03-19 | GSE52256 | GEO