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:Dietary protein is a critical regulator of metabolic health and aging in diverse species, and many of the benefits of low-protein diets are recapitulated by restriction of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine. In mouse models of Alzheimer’s disease (AD), dietary supplementation with BCAAs worsens AD neuropathology, while restriction of any of the BCAAs improves cognitive deficits. We recently discovered that each BCAA has distinct metabolic effects, with the restriction of isoleucine alone being sufficient to improve metabolic health and extend lifespan and healthspan in genetically diverse mice. Here, we investigate the effect of restricting each individual BCAA on metabolic health and the development and progression of AD in the 3xTg mouse model. We find that restriction of isoleucine and valine, but not leucine, promotes metabolic health. Restricting any of the three BCAAs improved short-term memory in males, with isoleucine restriction having the strongest effect, while restricting valine has the greatest cognitive benefits in females. Restriction of each BCAA had distinct effects on AD pathology, mTOR signaling, autophagy, and survival. Transcriptomic analysis of the brain revealed both distinct and shared, and highly sex-specific, molecular impacts of restricting each BCAA, and we identify a set of significantly altered pathways strongly associated with reduced AD pathology and improved cognitive performance in males. Our findings suggest that restricting any of the BCAAs, particularly isoleucine or valine, may form the basis of a novel sex-specific approach to prevent or delay the progression of AD.
2025-07-30 | GSE299928 | GEO
Project description:Cells regulate protein synthesis in response to fluctuating nutrient availability through highly coordinated mechanisms that affect both translation initiation and elongation. Branched-chain amino acids (BCAAs) - leucine, isoleucine, and valine - are essential nutrients with a significant impact on cellular physiology. However, how their simultaneous depletion affects the translational machinery and dynamics remains largely unclear. Here, we examine the immediate effects of short-term BCAA limitation on translational dynamics in mammalian cells. We performed RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) on NIH3T3 cells subjected to single, double, or triple BCAA deprivation. Our analyses revealed increased ribosome dwell times in the deprived conditions, with especially strong stalling at all valine codons during valine and triple starvation, while leucine and isoleucine depletion triggered more moderate, codon-specific effects. Notably, isoleucine-specific stalling largely diminished under triple deprivation, likely due to early elongation bottlenecks at valine codons. Correlating these stalling events with tRNA charging levels revealed distinct tRNA isoacceptor regulation in each starvation condition. In addition, integrating proteome data showed that many proteins downregulated under BCAA deprivation harbor stalling sites, suggesting that compromised elongation contributes to decreased protein output. Together, these findings suggest that differential ribosome stalling under BCAA limitation reflects a balance between amino acid supply, tRNA charging dynamics, and stress pathway modulation, illustrating that codon usage biases can profoundly influence the global landscape of translation under nutrient stress.
2025-09-02 | GSE291653 | GEO
Project description:Cells regulate protein synthesis in response to fluctuating nutrient availability through highly coordinated mechanisms that affect both translation initiation and elongation. Branched-chain amino acids (BCAAs) - leucine, isoleucine, and valine - are essential nutrients with a significant impact on cellular physiology. However, how their simultaneous depletion affects the translational machinery and dynamics remains largely unclear. Here, we examine the immediate effects of short-term BCAA limitation on translational dynamics in mammalian cells. We performed RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) on NIH3T3 cells subjected to single, double, or triple BCAA deprivation. Our analyses revealed increased ribosome dwell times in the deprived conditions, with especially strong stalling at all valine codons during valine and triple starvation, while leucine and isoleucine depletion triggered more moderate, codon-specific effects. Notably, isoleucine-specific stalling largely diminished under triple deprivation, likely due to early elongation bottlenecks at valine codons. Correlating these stalling events with tRNA charging levels revealed distinct tRNA isoacceptor regulation in each starvation condition. In addition, integrating proteome data showed that many proteins downregulated under BCAA deprivation harbor stalling sites, suggesting that compromised elongation contributes to decreased protein output. Together, these findings suggest that differential ribosome stalling under BCAA limitation reflects a balance between amino acid supply, tRNA charging dynamics, and stress pathway modulation, illustrating that codon usage biases can profoundly influence the global landscape of translation under nutrient stress.
2025-09-02 | GSE291652 | GEO
Project description:Correct charging of tRNAs with their corresponding amino acid is crucial for accurate translation of the genetic code into proteins. However, a growing body of evidence shows that unicellular organisms (bacteria and yeast) can sacrifice translational fidelity to preserve protein synthesis under deprivation of specific essential amino acids.1 Several weeks ago, Pataskar and colleagues described the first instance of codon reassignments caused by amino acid restriction in mammalian cells. Specifically, when human cancer cells were deprived of tryptophan (W), tRNATrp was misacylated with the structurally similar amino acid phenylalanine (F) by tryptophanyl-tRNA synthetase (WARS1), resulting in W>F substitutions in synthesized proteins.2 The authors show that W>F substitutions do preserve translation, but generally result in dysfunctional proteins and that presentation of W>F peptides stimulates T cell-mediated killing. Together this would impair survival of cancer cells that incorporate W>F substitutions in their proteome.2 In the context of growing interest in amino acid depletion diets and related disorders,2 we wondered whether amino acid substitutions are restricted to pathological states like cancer or may represent a more generalized mechanism to maintain translation despite unfavorable circumstances. It is known that ARSs can misactivate tRNAs with structurally similar amino acids3, but editing activity ensures extreme specificity under physiological conditions.4,5 Given the structural similarities between isoleucine and valine, we speculated that isoleucyl-tRNA synthetase (IARS1) would misacylate tRNAIle with valine under isoleucine restriction, leading to I>V substitutions in the proteome. Not only did these substitutions occur in healthy primary human cells, but they also preserved translation and promoted cell viability upon nutritional stress.
2024-11-26 | PXD033426 | Pride
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
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 aro8M-oM-^AM-^D 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. The goal of the present study was to identify genes that influence the transcriptional (de)repression of the Ehrlich pathway during growth with ammonium as the nitrogen source. With the aid of Synthetic Genetic Array technology, we constructed a strain collection in which deletions in the non-essential genes in the S. cerevisiae genome were combined with a reporter plasmid comprising the ARO10 promoter fused to a reporter gene (egfp) encoding a fluorescent reporter protein. After screening by flow cytometry, deletion of ARO8 led to a deregulated expression from the ARO10 promoter. The impact of this deletion was further studied by transcriptome and intracellular metabolite analyses. Furthermore, phenylethanol production was measured in strains that combined the aro8 mutation with mutations that were previously shown to deregulate aromatic amino acid biosynthesis.
2014-03-19 | E-GEOD-52256 | biostudies-arrayexpress
Project description:Amino Acid Conjugated Surfaces and Controls 32 Hours Time Point Keywords: parallel sample
2004-01-28 | GSE999 | GEO
Project description:Amino Acid Conjugated Surfaces and Controls at Time point 6 hours Keywords: parallel sample
2004-01-28 | GSE998 | GEO