PubMed

Related Articles Toward automated chromatographic fingerprinting: A non-alignment approach to gas chromatography mass spectrometry data. Anal Chim Acta. 2016 Mar 10;911:42-58 Authors: Vestner J, de Revel G, Krieger-Weber S, Rauhut D, du Toit M, de Villiers A Abstract In contrast to targeted analysis of volatile compounds, non-targeted approaches take information of known and unknown compounds into account, are inherently more comprehensive and give a more holistic representation of the sample composition. Although several non-targeted approaches have been developed, there's still a demand for automated data processing tools, especially for complex multi-way data such as chromatographic data obtained from multichannel detectors. This work was therefore aimed at developing a data processing procedure for gas chromatography mass spectrometry (GC-MS) data obtained from non-targeted analysis of volatile compounds. The developed approach uses basic matrix manipulation of segmented GC-MS chromatograms and PARAFAC multi-way modelling. The approach takes retention time shifts and peak shape deformations between samples into account and can be done with the freely available N-way toolbox for MATLAB. A demonstration of the new fingerprinting approach is presented using an artificial GC-MS data set and an experimental full-scan GC-MS data set obtained for a set of experimental wines. PMID: 26893085 [PubMed - in process]

Related Articles Variable importance analysis based on rank aggregation with applications in metabolomics for biomarker discovery. Anal Chim Acta. 2016 Mar 10;911:27-34 Authors: Yun YH, Deng BC, Cao DS, Wang WT, Liang YZ Abstract Biomarker discovery is one important goal in metabolomics, which is typically modeled as selecting the most discriminating metabolites for classification and often referred to as variable importance analysis or variable selection. Until now, a number of variable importance analysis methods to discover biomarkers in the metabolomics studies have been proposed. However, different methods are mostly likely to generate different variable ranking results due to their different principles. Each method generates a variable ranking list just as an expert presents an opinion. The problem of inconsistency between different variable ranking methods is often ignored. To address this problem, a simple and ideal solution is that every ranking should be taken into account. In this study, a strategy, called rank aggregation, was employed. It is an indispensable tool for merging individual ranking lists into a single "super"-list reflective of the overall preference or importance within the population. This "super"-list is regarded as the final ranking for biomarker discovery. Finally, it was used for biomarkers discovery and selecting the best variable subset with the highest predictive classification accuracy. Nine methods were used, including three univariate filtering and six multivariate methods. When applied to two metabolic datasets (Childhood overweight dataset and Tubulointerstitial lesions dataset), the results show that the performance of rank aggregation has improved greatly with higher prediction accuracy compared with using all variables. Moreover, it is also better than penalized method, least absolute shrinkage and selectionator operator (LASSO), with higher prediction accuracy or less number of selected variables which are more interpretable. PMID: 26893083 [PubMed - in process]

Related Articles Soft Corals Biodiversity in the Egyptian Red Sea: a Comparative MS and NMR Metabolomics Approach of Wild and Aquarium Grown Species. J Proteome Res. 2016 Feb 19; Authors: Farag MA, Porzel A, Al-Hammady MA, Hegazy MF, Meyer A, Mohamed TA, Westphal H, Wessjohann LA Abstract Marine life has developed unique metabolic and physiologic capabilities and advanced symbiotic relationships to survive in the varied and complex marine ecosystems. Herein, metabolite composition of the soft coral genus Sarcophyton was profiled with respect to its species, and different habitats along the coastal Egyptian Red Sea via 1H-NMR and UPLC-MS large-scale metabolomics analyses. Current study extends the application of comparative secondary metabolite profiling from plants to corals to reveal for metabolite compositional differences among its species, using a novel comparative MS and NMR approach (COMET). This was applied for the first time to investigate the metabolism of 16 Sarcophyton species in the context of their genetic diversity and growth habitat. Under optimized conditions, we were able to simultaneously identify 120 metabolites including sixty five diterpenes (65), eight sesquiterpenes (8), eighteen sterols (18) and fifteen oxylipids (15). Principal component analysis (PCA), hierarchical clustering analysis (HCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were used to define both similarities and differences among samples. For corals classification based on species type, UPLC-MS was found to be more effective than NMR. The main differentiations emanate from cembranoids and oxylipids. The specific markers that contribute to discrimination between soft corals of S. ehrenbergi from 3 different growing habitats also belonged to cembrane type diterpenes, with aquarium S. ehrenbergi corals being less enriched in cembranoids compared to sea corals. PCA analysis using either NMR or UPLC-MS datasets was found equally effective in predicting the species origin of unknown Sarcophyton species. Cyclopropane containing sterols observed in abundance in the corals may act as cellular membrane protectant against the action of coral toxins, i.e. cembranoids. PMID: 26892921 [PubMed - as supplied by publisher]

Related Articles Abdominal obesity and circulating metabolites: A twin study approach. Metabolism. 2016 Mar;65(3):111-21 Authors: Bogl LH, Kaye SM, Rämö JT, Kangas AJ, Soininen P, Hakkarainen A, Lundbom J, Lundbom N, Ortega-Alonso A, Rissanen A, Ala-Korpela M, Kaprio J, Pietiläinen KH Abstract OBJECTIVE: To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. SUBJECTS AND METHODS: Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (rg) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference ≥3kg/m(2)). RESULTS: Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (rg=0.40), glycoprotein (rg=0.37), serum triglycerides (rg=0.36), BCAAs (rg=0.30-0.40), HDL particle diameter (rg=-0.33) and HDL cholesterol (rg=-0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. CONCLUSIONS: A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. PMID: 26892522 [PubMed - in process]

Related Articles CE-MS in metabolomics: status quo and the way forward. Bioanalysis. 2016 Feb 19; Authors: Ramautar R PMID: 26891881 [PubMed - as supplied by publisher]

Related Articles Metabolomics in diabetic complications. Mol Biosyst. 2016 Feb 19; Authors: Filla LA, Edwards JL Abstract With a global prevalence of 9%, diabetes is the direct cause of millions of deaths each year and is quickly becoming a health crisis. Major long-term complications of diabetes arise from persistent oxidative stress and dysfunction in multiple metabolic pathways. The most serious complications involve vascular damage and include cardiovascular disease as well as microvascular disorders such as nephropathy, neuropathy, and retinopathy. Current clinical analyses like glycated hemoglobin and plasma glucose measurements hold some value as prognostic indicators of the severity of complications, but investigations into the underlying pathophysiology are still lacking. Advancements in biotechnology hold the key to uncovering new pathways and establishing therapeutic targets. Metabolomics, the study of small endogenous molecules, is a powerful toolset for studying pathophysiological processes and has been used to elucidate metabolic signatures of diabetes in various biological systems. Current challenges in the field involve correlating these biomarkers to specific complications to provide a better prediction of future risk and disease progression. This review will highlight the progress that has been made in the field of metabolomics including technological advancements, the identification of potential biomarkers, and metabolic pathways relevant to macro- and microvascular diabetic complications. PMID: 26891794 [PubMed - as supplied by publisher]

Related Articles MALDI mass spectrometric imaging meets "omics": recent advances in the fruitful marriage. Analyst. 2015 Sep 7;140(17):5806-20 Authors: Crecelius AC, Schubert US, von Eggeling F Abstract Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI MSI) is a method that allows the investigation of the molecular content of surfaces, in particular, tissues, within its morphological context. The applications of MALDI MSI in the field of large-scale mass spectrometric studies, which are typically denoted by the suffix "omics", are steadily increasing. This is because, on the one hand, technical advances regarding sample collection and preparation, matrix application, instrumentation, and data processing have enhanced the molecular specificity and sensitivity of MALDI MSI; on the other hand, the focus of the "omics" community has moved from establishing an inventory of certain compound classes to exploring their spatial distribution to gain novel insights. Thus, the aim of this mini-review is twofold, to display the state-of-the-art in terms of technical aspects in MALDI MSI and to highlight selected applications in the last two years, which either have significantly advanced a certain "omics" field or have introduced a new one through pioneering efforts. PMID: 26161715 [PubMed - indexed for MEDLINE]

Related Articles The use of an acetoacetyl-CoA synthase in place of a β-ketothiolase enhances poly-3-hydroxybutyrate production in sugarcane mesophyll cells. Plant Biotechnol J. 2015 Jun;13(5):700-7 Authors: McQualter RB, Petrasovits LA, Gebbie LK, Schweitzer D, Blackman DM, Chrysanthopoulos P, Hodson MP, Plan MR, Riches JD, Snell KD, Brumbley SM, Nielsen LK Abstract Engineering the production of polyhydroxyalkanoates (PHAs) into high biomass bioenergy crops has the potential to provide a sustainable supply of bioplastics and energy from a single plant feedstock. One of the major challenges in engineering C4 plants for the production of poly[(R)-3-hydroxybutyrate] (PHB) is the significantly lower level of polymer produced in the chloroplasts of mesophyll (M) cells compared to bundle sheath (BS) cells, thereby limiting the full PHB yield-potential of the plant. In this study, we provide evidence that the access to substrate for PHB synthesis may limit polymer production in M chloroplasts. Production of PHB in M cells of sugarcane is significantly increased by replacing β-ketothiolase, the first enzyme in the bacterial PHA pathway, with acetoacetyl-CoA synthase. This novel pathway enabled the production of PHB reaching an average of 6.3% of the dry weight of total leaf biomass, with levels ranging from 3.6 to 11.8% of the dry weight (DW) of individual leaves. These yields are more than twice the level reported in PHB-producing sugarcane containing the β-ketothiolase and illustrate the importance of producing polymer in mesophyll plastids to maximize yield. The molecular weight of the polymer produced was greater than 2 × 10(6)  Da. These results are a major step forward in engineering a high biomass C4 grass for the commercial production of PHB. PMID: 25532451 [PubMed - indexed for MEDLINE]

Related Articles The Time Is Right to Focus on Model Organism Metabolomes. Metabolites. 2016;6(1) Authors: Edison AS, Hall RD, Junot C, Karp PD, Kurland IJ, Mistrik R, Reed LK, Saito K, Salek RM, Steinbeck C, Sumner LW, Viant MR Abstract Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research. PMID: 26891337 [PubMed - as supplied by publisher]

Related Articles Metabolomics study of Roux-en-Y gastric bypass surgery (RYGB) to treat type 2 diabetes patients based on ultra performance liquid chromatography-mass spectrometry. J Proteome Res. 2016 Feb 18; Authors: Luo P, Yu H, Zhao X, Bao Y, Hong CS, Zhang P, Tu Y, Yin P, Gao P, Wei L, Zhuang Z, Jia W, Xu G Abstract Roux-en-Y gastric bypass (RYGB) is one of the most effective treatments for long-term weight loss and diabetes remission. However, the mechanisms underlying these changes are not clearly understood. In this study, the serum metabolic profiles of 23 remission and 12 non-remission patients with type 2 diabetes mellitus (T2DM) were measured at baseline, 6- and 12-months after RYGB. A metabolomics analysis was performed based on ultra performance liquid chromatography-mass spectrometry. Clinical improvements in insulin sensitivity, energy metabolism, and inflammation were related to metabolic alterations of free fatty acids (FFA), acylcarnitines, amino acids, bile acids and lipids species. Differential metabolic profiles were observed between the two T2DM subgroups, and patients with severity fat accumulation and oxidation stress may be more suitable for RYGB. Baseline levels of tryptophan, bilirubin, and indoxyl sulfate measured prior to surgery as well as levels of FFA 16:0, FFA 18:3, FFA 17:2 and hippuric acid measured at 6-months after surgery best predicted the suitability and efficacy of RYGB for patients with T2DM. These metabolites represent potential biomarkers that may be clinically helpful in individualized treatment for T2DM patients by RYGB. PMID: 26889720 [PubMed - as supplied by publisher]

Related Articles Reduced mitochondrial malate dehydrogenase activity has a strong effect on photorespiratory metabolism as revealed by 13C labelling. J Exp Bot. 2016 Feb 17; Authors: Lindén P, Keech O, Stenlund H, Gardeström P, Moritz T Abstract Mitochondrial malate dehydrogenase (mMDH) catalyses the interconversion of malate and oxaloacetate (OAA) in the tricarboxylic acid (TCA) cycle. Its activity is important for redox control of the mitochondrial matrix, through which it may participate in regulation of TCA cycle turnover. In Arabidopsis, there are two isoforms of mMDH. Here, we investigated to which extent the lack of the major isoform, mMDH1 accounting for about 60% of the activity, affected leaf metabolism. In air, rosettes of mmdh1 plants were only slightly smaller than wild type plants although the fresh weight was decreased by about 50%. In low CO2 the difference was much bigger, with mutant plants accumulating only 14% of fresh weight as compared to wild type. To investigate the metabolic background to the differences in growth, we developed a (13)CO2 labelling method, using a custom-built chamber that enabled simultaneous treatment of sets of plants under controlled conditions. The metabolic profiles were analysed by gas- and liquid- chromatography coupled to mass spectrometry to investigate the metabolic adjustments between wild type and mmdh1. The genotypes responded similarly to high CO2 treatment both with respect to metabolite pools and (13)C incorporation during a 2-h treatment. However, under low CO2 several metabolites differed between the two genotypes and, interestingly most of these were closely associated with photorespiration. We found that while the glycine/serine ratio increased, a concomitant altered glutamine/glutamate/α-ketoglutarate relation occurred. Taken together, our results indicate that adequate mMDH activity is essential to shuttle reductants out from the mitochondria to support the photorespiratory flux, and strengthen the idea that photorespiration is tightly intertwined with peripheral metabolic reactions. PMID: 26889011 [PubMed - as supplied by publisher]

Related Articles Development of Real-Time RT-PCR Assays for Detection and Typing of Epizootic Haemorrhagic Disease Virus. Transbound Emerg Dis. 2016 Feb 17; Authors: Maan NS, Maan S, Potgieter AC, Wright IM, Belaganahalli M, Mertens PP Abstract Epizootic haemorrhagic disease virus (EHDV) is an emerging arboviral pathogen of wild and domestic ruminants worldwide. It is closely related to bluetongue virus (BTV) and is transmitted by adult females of competent Culicoides vector species. The EHDV genome consists of ten linear double-stranded (ds)RNA segments, encoding five non-structural and seven structural proteins. Genome-segment reassortment contributes to a high level of genetic variation in individual virus strains, particularly in the areas where multiple and distinct virus lineages co-circulate. In spite of the relatively close relationship between BTV and EHDV herd-immunity to BTV does not appear to protect against the introduction and infection of animals by EHDV. Although EHDV can cause up to 80% morbidity in affected animals, vaccination with the homologous EHDV serotype is protective. Outer-capsid protein VP2, encoded by Seg-2, is the most variable of the EHDV proteins and determines both the specificity of reactions with neutralizing antibodies and consequently the identity of the eight EHDV serotypes. In contrast, VP6 (the viral helicase), encoded by Seg-9, is highly conserved, representing a virus species/serogroup-specific antigen. We report the development and evaluation of quantitative (q)RT-PCR assays targeting EHDV Seg-9 that can detect all EHDV strains (regardless of geographic origin/topotype/serotype), as well as type-specific assays targeting Seg-2 of the eight EHDV serotypes. The assays were evaluated using orbivirus isolates from the 'Orbivirus reference collection' (ORC) at The Pirbright Institute and were shown to be EHDV pan-reactive or type-specific. They can be used for rapid, sensitive and reliable detection and identification (typing) of EHDV RNA from infected blood, tissue samples, homogenized Culicoides, or tissue culture supernatant. None of the assays detected RNA from closely related but heterologous orbiviruses, or from uninfected host animals or cell cultures. The techniques presented could be used for both surveillance and vaccine matching (serotype identification) as part of control strategies for incursions in wild and domestic animal species. PMID: 26888716 [PubMed - as supplied by publisher]

Related Articles Metabolomics Study of Type 2 Diabetes Mellitus and the AntiDiabetic Effect of Berberine in Zucker Diabetic Fatty Rats Using Uplc-ESI-Hdms. Phytother Res. 2016 Feb 16; Authors: Dong Y, Chen YT, Yang YX, Zhou XJ, Dai SJ, Tong JF, Shou D, Li C Abstract The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti-diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra-performance liquid chromatography/electrospray ionization synapt high-definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as 'differentiating metabolites' with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near-normal state. These results suggested that the anti-diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5'-monophosphate-activated protein kinase. Our work not only provides a better understanding of the anti-diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 26888689 [PubMed - as supplied by publisher]

Related Articles Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study. Leuk Lymphoma. 2016 Feb 17;:1-9 Authors: Stenson M, Pedersen A, Hasselblom S, Nilsson-Ehle H, Karlsson BG, Pinto R, Andersson PO Abstract The prognosis for diffuse large B-cell lymphoma (DLBCL) patients with early relapse or refractory disease is dismal. To determine if clinical outcome correlated to diverse serum metabolomic profiles, we used (1)H nuclear magnetic resonance (NMR) spectroscopy and compared two groups of DLBCL patients treated with immunochemotherapy: i) refractory/early relapse (REF/REL; n=27) and ii) long-term progression-free (CURED; n = 60). A supervised multivariate analysis showed a separation between the groups. Among discriminating metabolites higher in the REF/REL group were the amino acids lysine and arginine, the degradation product cadaverine and a compound in oxidative stress (2-hydroxybutyrate). In contrast, the amino acids aspartate, valine and ornithine, and a metabolite in the glutathione cycle, pyroglutamate, were higher in CURED patients. Together, our data indicate that NMR-based serum metabolomics can identify a signature for DLBCL patients with high-risk of failing immunochemotherapy, prompting for larger validating studies which could lead to more individualized treatment of this disease. PMID: 26887805 [PubMed - as supplied by publisher]

Related Articles Effect of metformin therapy on circulating amino acids in a randomized trial: the CAMERA study: Metabolism. Diabet Med. 2016 Feb 16; Authors: Preiss D, Rankin N, Welsh P, Holman RR, Kangas AJ, Soininen P, Würtz P, Ala-Korpela M, Sattar N Abstract AIMS: To investigate whether metformin therapy alters amino acid concentrations, increased levels of which have been found to predict Type 2 diabetes. METHODS: In the Carotid Atherosclerosis: Metformin for Insulin Resistance (CAMERA) study (NCT00723307), 173 individuals without Type 2 diabetes, but with coronary disease, were randomized to metformin (n=86) or placebo (n=87) for 18 months. Plasma samples, taken every 6 months, were analysed using quantitative nuclear magnetic resonance spectroscopy. Ten metabolites consisting of eight amino acids [three branched-chain (isoleucine, leucine, valine), three aromatic (tyrosine, phenylalanine, histidine) and two other amino acids (alanine, glutamine)], lactate and pyruvate were quantified and analysed using repeated-measures models. On-treatment analyses were conducted to investigate whether amino acid changes were dependent on changes in weight, fat mass or insulin resistance measured using homeostasis model assessment. RESULTS: Tyrosine decreased [-6.1 μmol/l (95% CI -8.5, -3.7); P<0.0001], while alanine [42 umol/l (95% CI 25, 59); P<0.0001] increased in the metformin-treated group compared with the placebo-treated group. Decreases in phenylalanine [-2.0 μmol/l (95% CI -3.6, -0.3); P=0.018] and increases in histidine [2.3 μmol/l (95% CI 0.1, 4.6); P=0.045] were also observed in the metformin group, although these changes were less statistically robust. No changes in these four amino acids were accounted for by changes in weight, fat mass or homeostasis model assessment of insulin resistance values. Levels of branched-chain amino acids, glutamine, pyruvate and lactate were not altered by metformin therapy. CONCLUSIONS: Metformin therapy results in a sustained and specific pattern of changes in aromatic amino acid and alanine concentrations. These changes are independent of any effects on weight and insulin sensitivity. Any causal link to metformin's unexplained cardiometabolic benefit requires further study. This article is protected by copyright. All rights reserved. PMID: 26887663 [PubMed - as supplied by publisher]

Related Articles Uwe Sauer. Nat Methods. 2015 Nov;12(11):997 Authors: Marx V PMID: 26824101 [PubMed - indexed for MEDLINE]

Related Articles [Metabolic regulation of stem cells]. Rinsho Ketsueki. 2015 Oct;56(10):1882-7 Authors: Takubo K Abstract Stem cells activate various metabolic programs and acquire ATP and metabolites to maintain self-renewal and multi-differentiation capacities. Pluripotent stem cells and hematopoietic stem cells have recently been shown to have specific metabolic features different from those of differentiated cells. These metabolic features themselves drive stem cell-specific characteristics. Thus, integrative understandings of metabolic regulation of stem cells are essential for the development of technologies for ex vivo expansion of stem cells, efficient induction of differentiated cells from stem cells and targeted therapies aimed at controlling and eliminating tumor-initiating cells. PMID: 26458425 [PubMed - indexed for MEDLINE]

Related Articles Real-time metabolome profiling of the metabolic switch between starvation and growth. Nat Methods. 2015 Nov;12(11):1091-7 Authors: Link H, Fuhrer T, Gerosa L, Zamboni N, Sauer U Abstract Metabolic systems are often the first networks to respond to environmental changes, and the ability to monitor metabolite dynamics is key for understanding these cellular responses. Because monitoring metabolome changes is experimentally tedious and demanding, dynamic data on time scales from seconds to hours are scarce. Here we describe real-time metabolome profiling by direct injection of living bacteria, yeast or mammalian cells into a high-resolution mass spectrometer, which enables automated monitoring of about 300 compounds in 15-30-s cycles over several hours. We observed accumulation of energetically costly biomass metabolites in Escherichia coli in carbon starvation-induced stationary phase, as well as the rapid use of these metabolites upon growth resumption. By combining real-time metabolome profiling with modeling and inhibitor experiments, we obtained evidence for switch-like feedback inhibition in amino acid biosynthesis and for control of substrate availability through the preferential use of the metabolically cheaper one-step salvaging pathway over costly ten-step de novo purine biosynthesis during growth resumption. PMID: 26366986 [PubMed - indexed for MEDLINE]

Related Articles NMR-Based Metabolomic Analysis of Huanglongbing-Asymptomatic and -Symptomatic Citrus Trees. J Agric Food Chem. 2015 Sep 2;63(34):7582-8 Authors: Freitas Ddos S, Carlos EF, Gil MC, Vieira LG, Alcantara GB Abstract Huanglongbing (HLB) is one of the most severe diseases that affects citrus trees worldwide and is associated with the yet uncultured bacteria Candidatus Liberibacter spp. To assess the metabolomic differences between HLB-asymptomatic and -symptomatic tissues, extracts from leaf and root samples taken from a uniform 6-year-old commercial orchard of Valencia trees were subjected to nuclear magnetic resonance (NMR) and chemometrics. The results show that the symptomatic trees had higher sucrose content in their leaves and no variation in their roots. In addition, proline betaine and malate were detected in smaller amounts in the HLB-affected symptomatic leaves. The changes in metabolic processes of the plant in response to HLB are corroborated by the relationship between the bacterial levels and the metabolic profiles. PMID: 26285838 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiles of dioscin in rats revealed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Biomed Chromatogr. 2015 Sep;29(9):1415-21 Authors: Zhu H, Xu JD, Mao Q, Shen H, Kong M, Chen JP, Li SL Abstract Dioscin (DIS), one of the most abundant bioactive steroidal saponins in Dioscorea sp., is used as a complementary medicine to treat coronary disease and angina pectoris in China. Although the pharmacological activities and pharmacokinetics of DIS have been well demonstrated, information regarding the final metabolic fates is very limited. This study investigated the in vivo metabolic profiles of DIS after oral administration by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method. The structures of the metabolites were identified and tentatively characterized by means of comparing the molecular mass, retention time and fragmentation pattern of the analytes with those of the parent compound. A total of eight metabolites, including seven phase I and one phase II metabolites, were detected and tentatively identified for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. In addition, a possible metabolic pathway on the biotransformation of DIS in vivo was proposed. This study provides valuable and new information on the metabolism of DIS, which will be helpful for further understanding its mechanism of action. PMID: 25678372 [PubMed - indexed for MEDLINE]