Development and Quantitative Evaluation of a High-Resolution Metabolomics Technology

Liu, Xiaojing; Ser, Zheng; Locasale, Jason W.

doi:10.1021/ac403845u

Cited by 173 publications

(208 citation statements)

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“…Tregs can also induce dendritic cells to consume essential amino acids, which inhibits T cell proliferation (35 Metabolomics and acyl-carnitines. Nontargeted metabolomic analyses were performed as described using LC Q Exactive Mass Spectrometer (LC-QE-MS) (Thermo Scientific) (24). Additional metabolomics analysis was performed using GC/MS and LC/MS/MS platforms (Metabolon Inc.) for determination of cellular metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…We therefore examined metabolite levels and metabolic gene expression of Th1 and Th17 cells and Tregs in detail, as the balance of these subtypes is crucial in a variety of inflammatory settings. Unsupervised clustering of steady-state levels of approximately 400 metabolites measured by high-resolution nontargeted Q exactive-mass spectrometry (QE-MS) metabolomics (24) showed that Teffs and Tregs had broad metabolic differences ( Figure 4A and Supplemental Table 1). Importantly, Tregs were dissimilar from Th1 and Th17 cells, which clustered together.…”

Section: Inhibition Of Glycolysis or Mitochondrial Oxidation Selectivmentioning

confidence: 99%

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Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Section: Inhibition Of Glycolysis or Mitochondrial Oxidation Selectivmentioning

confidence: 99%

Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation

et al. 2014

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“…http://dx.doi.org/10.1101/259523 doi: bioRxiv preprint first posted online Feb. 4, 2018; method (HILIC) with an Xbridge amide column (100 x 2.1 mm i.d., 3.5 µm; Waters) was used for compound separation at room temperature. The mobile phase and gradient information were described previously 45 . 2-hydrazinoquinoline derivatives were measured using reversed phase LC method, which employed an Acclaim RSLC 120 C8 reversed phase column (150 x 2.1 mm i.d., 2.2 µm; Dionex) with mobile phase A: water with 0.5 % formic acid, and mobile phase B: acetonitrile.…”

Section: Disclosuresmentioning

confidence: 99%

De novo acetate production is coupled to central carbon metabolism in mammals

Liu

et al. 2018

Preprint

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In cases of nutritional excess, there is incomplete catabolism of a nutritional source and secretion of a waste product (overflow metabolism), such as the conversion of glucose to lactate (the Warburg Effect) in tumors. Here we report that excess glucose metabolism generates acetate, a key nutrient whose source has been unclear. Conversion of pyruvate, the product of glycolysis, to acetate occurs through two mechanisms: 1) coupling to reactive oxygen species (ROS), and 2) a neomorphic enzyme activity from keto acid dehydrogenases that enable it to function as a pyruvate decarboxylase. Furthermore, we demonstrate that glucose-derived acetate is sufficient to maintain acetyl-coenzyme A (Ac-CoA) pools and cell proliferation in certain limited metabolic environments such as during mitochondrial dysfunction or ATP citrate lyase (ACLY) deficiency. Thus, de novo acetate production is coupled to the activity of central carbon metabolism providing possible regulatory mechanisms and links to pathophysiology.peer-reviewed)

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“…We therefore developed a novel method for sensitive, rapid, and quantitative acyl-CoA profiling, with a compatible sample preparation procedure that has been previously shown for polar metabolite analysis (18). The method involves LC-MS using reversed phase chromatographic separation coupled to a high-resolution Orbitrap mass spectrometer with label free quantitation.…”

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High-Resolution Metabolomics with Acyl-CoA Profiling Reveals Widespread Remodeling in Response to Diet*

Liu

Sadhukhan

Sun

et al. 2015

Molecular & Cellular Proteomics

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The availability of acyl-Coenzyme A (acyl-CoA) thioester compounds affects numerous cellular functions including autophagy, lipid oxidation and synthesis, and post-translational modifications. Consequently, the acyl-CoA level changes tend to be associated with other metabolic alterations that regulate these critical cellular functions. Despite their biological importance, this class of metabolites remains difficult to detect and quantify using current analytical methods. Here we show a universal method for metabolomics that allows for the detection of an expansive set of acyl-CoA compounds and hundreds of other cellular metabolites. We apply this method to profile the dynamics of acyl-CoA compounds and corresponding alterations in metabolism across the metabolic network in response to high fat feeding in mice. We identified targeted metabolites (>50) and untargeted features (>1000) with significant changes ( Thioester compounds containing acyl-coenzyme A (acylCoA) 1 are key metabolites in intermediary metabolism. The most prominent of which is acetyl-CoA whose levels regulate critical cellular processes such as energy metabolism, protein acetylation, lipid synthesis and catabolism, and even autophagy (1-4). Other acyl-CoA compounds are also increasingly appreciated as playing important roles in diverse cellular processes (5-8). These compounds are generated from multiple pathways, such as glycolysis, the citric acid cycle (TCA cycle), beta-oxidation, and branched chain amino acid catabolism. As the acyl group carrier, acyl-CoA can partake in chemical reactions on proteins including histones resulting in mediation of chromatin biology. Therefore, considerable effort has been spent on developing methods for acyl-CoA and corresponding acyl protein modification measurements (9 -17). Liquid chromatography coupled to mass spectrometry (LC-MS) is the most frequently used method for small molecule analysis in large part because of superior sensitivity. Moreover, LC-MS analysis can handle a broad range of complex biological mixtures and the analysis is relatively easier compared with many other methods, such as NMR, scintillation counting, and UV detection.Reversed phase LC coupled to a triple quadrupole mass spectrometer has been frequently used as for targeted measurements of specific acyl-CoA compounds, because acylCoA compounds undergo a common fragmentation, the neutral loss of adenosine diphosphate, which is the basis of multiple reaction monitoring for acyl-CoA measurements. Especially when stable isotope labeled acyl-CoA standards are used, this method has shown high accuracy and precision (11,14). However, these methods involve several laborious steps of sample purification and enrichment before LC-MS analysis, such as solid phase extraction, which in addition to often being time-and cost-prohibitive, can also result in poor sensitivity and accuracy because of imperfect metabolite recovery. Moreover, reversed phase ion-paired chromatograFrom the ‡Division

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Development and Quantitative Evaluation of a High-Resolution Metabolomics Technology

Cited by 173 publications

References 36 publications

Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation

Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation

De novo acetate production is coupled to central carbon metabolism in mammals

High-Resolution Metabolomics with Acyl-CoA Profiling Reveals Widespread Remodeling in Response to Diet*

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