Special Issue "Response to Environment and Stress Metabolism"

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A special issue of Metabolites (ISSN 2218-1989).

Deadline for manuscript submissions: closed (30 June 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Teresa Fan

Department of Toxicology, Markey Cancer Center and Center for Environmental and Systems Biochemistry (CESB), University of Kentucky, Lexington, KY 40536, USA
Website | E-Mail
Interests: use of metabolomics and transcriptomics for probing metabolic regulation and adaptation in organisms in response to environmental perturbations; molecular mechanism of Se toxicity in the environment and chemoprevention in human cancers; translation of basic metabolic knowledge into functional diagnostic markers and molecular targets for cancers

Special Issue Information

Dear Colleagues,

Environmental stresses are inevitable factors of life that all organisms encounter. Successful adaptations to various physical, chemical, nutritional, and/or biological threats are essential to species survival and ability to occupy environmental niches. Stress metabolism is the functional outcome of altered genetic, protein, and substrate level regulation in response to environmental variables, in terms of chronic to acute conditions. However, our understanding of stress metabolism has been hampered by the lack of tools to interrogate the metabolome with sufficient coverage. Recent advances in metabolomics tools, principally nuclear magnetic resonance spectroscopy and mass spectrometry, have enabled large-scale characterization of metabolism in organisms ranging from single cells to humans under a variety of environmental conditions. By introducing stable isotope tracers and resolving isotope labeling patterns in various metabolites, large-scale reconstruction of metabolic networks can be achieved with little ambiguity to facilitate the elucidation of the underlying regulatory pathways. Together with genomic, epigenomic, transcriptomic, and proteomic advances, these metabolomic tools will help revolutionize stress metabolic research in the 21st century, whether dealing with indigenous or model organisms.

In this special issue of Metabolites, original papers are solicited that utilize metabolomics tools to explore stress metabolism and to elucidate its regulation in a wide range of biological systems and environmental conditions. Novel metabolomics methods or informatics tools that advance current state-of-science are also welcome.

Prof. Dr. Teresa W.-M. Fan
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charges (APC) is waived for well prepared manuscripts in 2012 and starting January 2013, the APC is 300 CHF per accepted paper. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • integration of transcriptomics, proteomics, and metabolomics
  • model cells and whole organisms
  • indigenous single cell and multi-cellular organisms
  • Stable isotope tracers
  • pathway elucidation
  • metabolic compartmentation
  • reconstruction of metabolic networks
  • environmental stressors of metabolism and stress responses
  • novel mass spectrometry and NMR methodologies for high content analysis
  • flux analysis and modeling
  • bioinformatic tools for metabolite assignment

Published Papers (5 papers)

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Research

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Open AccessArticle Fluxomics of the Eastern Oyster for Environmental Stress Studies
Metabolites 2014, 4(1), 53-70; doi:10.3390/metabo4010053
Received: 21 August 2013 / Revised: 27 November 2013 / Accepted: 19 December 2013 / Published: 7 January 2014
Cited by 5 | PDF Full-text (1347 KB) | HTML Full-text | XML Full-text
Abstract
The metabolism of 2-13C/15N-glycine and U-13C-glucose was determined in four tissue blocks (adductor muscle, stomach and digestive gland, mantle, and gills) of the Eastern oyster (Crassostrea virginica) using proton (1H) and carbon-13 (
[...] Read more.
The metabolism of 2-13C/15N-glycine and U-13C-glucose was determined in four tissue blocks (adductor muscle, stomach and digestive gland, mantle, and gills) of the Eastern oyster (Crassostrea virginica) using proton (1H) and carbon-13 (13C) nuclear magnetic resonance (NMR) spectroscopy. The oysters were treated in aerated seawater with three treatments (5.5 mM U-13C-glucose, 2.7 mM 2-13C/15N-glycine, and 5.5 mM U-13C-glucose plus 2.7 mM 2-13C/15N-glycine) and the relative mass balance and 13C fractional enrichments were determined in the four tissue blocks. In all tissues, glycine was metabolized by the glycine cycle forming serine exclusively in the mitochondria by the glycine cleavage system forming 2,3-13C-serine. In muscle, a minor amount of serine-derived pyruvate entered the Krebs cycle as substantiated by detection of a trace of 2,3-13C-aspartate. In all tissues, U-13C-glucose formed glycogen by glycogen synthesis, alanine by glycolysis, and glutamate and aspartate through the Krebs cycle. Alanine was formed exclusively from glucose via alanine transaminase and not glycine via alanine-glyoxylate transaminase. Based on isotopomer analysis, pyruvate carboxylase and pyruvate dehydrogenase appeared to be equal points for pyruvate entry into the Krebs cycle. In the 5.5 mM U-13C-glucose plus 2.7 mM 2-13C/15N-glycine emergence treatment used to simulate 12 h of “low tide”, oysters accumulated more 13C-labeled metabolites, including both anaerobic glycolytic and aerobic Krebs cycle intermediates. The aerobic metabolites could be the biochemical result of the gaping behavior of mollusks during emergence. The change in tissue distribution and mass balance of 13C-labeled nutrients (U-13C-glucose and 2-13C/15N-glycine) provides the basis for a new quantitative fluxomic method for elucidating sub-lethal environmental effects in marine organisms called whole body mass balance phenotyping (WoMBaP). Full article
(This article belongs to the Special Issue Response to Environment and Stress Metabolism)
Open AccessArticle 2-Hydrazinoquinoline as a Derivatization Agent for LC-MS-Based Metabolomic Investigation of Diabetic Ketoacidosis
Metabolites 2013, 3(4), 993-1010; doi:10.3390/metabo3040993
Received: 31 August 2013 / Revised: 21 September 2013 / Accepted: 10 October 2013 / Published: 31 October 2013
Cited by 10 | PDF Full-text (730 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Short-chain carboxylic acids, aldehydes and ketones are products and regulators of many important metabolic pathways. Their levels in biofluids and tissues reflect the status of specific metabolic reactions, the homeostasis of the whole metabolic system and the wellbeing of a biological entity. In
[...] Read more.
Short-chain carboxylic acids, aldehydes and ketones are products and regulators of many important metabolic pathways. Their levels in biofluids and tissues reflect the status of specific metabolic reactions, the homeostasis of the whole metabolic system and the wellbeing of a biological entity. In this study, the use of 2-hydrazinoquinoline (HQ) as a novel derivatization agent was explored and optimized for simultaneous liquid chromatography-mass spectrometry (LC-MS) analysis of carboxylic acids, aldehydes and ketones in biological samples. The formation of carboxylic acid derivative is attributed to the esterification reaction between HQ and a carboxyl group, while the production of aldehyde and ketone derivatives is through the formation of Schiff bases between HQ and a carbonyl group. The compatibility of HQ with biological samples was demonstrated by derivatizing urine, serum and liver extract samples. Using this HQ-based approach, the kinetics of type 1 diabetes-induced metabolic changes was characterized by the LC-MS-based metabolomic analysis of urine samples from streptozotocin (STZ)-treated mice. Subsequently, carboxylic acid, aldehyde and ketone metabolites associated with STZ-elicited disruption of nutrient and energy metabolism were conveniently identified and elucidated. Overall, HQ derivatization of carboxylic acids, aldehydes and ketones could serve as a useful tool for the LC-MS-based metabolomic investigation of endogenous metabolism. Full article
(This article belongs to the Special Issue Response to Environment and Stress Metabolism)
Open AccessArticle 1H NMR-Based Metabolomic Analysis of Sub-Lethal Perfluorooctane Sulfonate Exposure to the Earthworm, Eisenia fetida, in Soil
Metabolites 2013, 3(3), 718-740; doi:10.3390/metabo3030718
Received: 1 July 2013 / Revised: 15 July 2013 / Accepted: 19 August 2013 / Published: 27 August 2013
Cited by 4 | PDF Full-text (789 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
1H NMR-based metabolomics was used to measure the response of Eisenia fetida earthworms after exposure to sub-lethal concentrations of perfluorooctane sulfonate (PFOS) in soil. Earthworms were exposed to a range of PFOS concentrations (five, 10, 25, 50, 100 or 150 mg/kg) for
[...] Read more.
1H NMR-based metabolomics was used to measure the response of Eisenia fetida earthworms after exposure to sub-lethal concentrations of perfluorooctane sulfonate (PFOS) in soil. Earthworms were exposed to a range of PFOS concentrations (five, 10, 25, 50, 100 or 150 mg/kg) for two, seven and fourteen days. Earthworm tissues were extracted and analyzed by 1H NMR. Multivariate statistical analysis of the metabolic response of E. fetida to PFOS exposure identified time-dependent responses that were comprised of two separate modes of action: a non-polar narcosis type mechanism after two days of exposure and increased fatty acid oxidation after seven and fourteen days of exposure. Univariate statistical analysis revealed that 2-hexyl-5-ethyl-3-furansulfonate (HEFS), betaine, leucine, arginine, glutamate, maltose and ATP are potential indicators of PFOS exposure, as the concentrations of these metabolites fluctuated significantly. Overall, NMR-based metabolomic analysis suggests elevated fatty acid oxidation, disruption in energy metabolism and biological membrane structure and a possible interruption of ATP synthesis. These conclusions obtained from analysis of the metabolic profile in response to sub-lethal PFOS exposure indicates that NMR-based metabolomics is an excellent discovery tool when the mode of action (MOA) of contaminants is not clearly defined. Full article
(This article belongs to the Special Issue Response to Environment and Stress Metabolism)
Open AccessArticle Electrospray Quadrupole Travelling Wave Ion Mobility Time-of-Flight Mass Spectrometry for the Detection of Plasma Metabolome Changes Caused by Xanthohumol in Obese Zucker (fa/fa) Rats
Metabolites 2013, 3(3), 701-717; doi:10.3390/metabo3030701
Received: 3 June 2013 / Revised: 1 August 2013 / Accepted: 7 August 2013 / Published: 13 August 2013
Cited by 9 | PDF Full-text (1085 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study reports on the use of traveling wave ion mobility quadrupole time-of-flight (ToF) mass spectrometry for plasma metabolomics. Plasma metabolite profiles of obese Zucker fa/fa rats were obtained after the administration of different oral doses of Xanthohumol; a hop-derived dietary supplement. Liquid
[...] Read more.
This study reports on the use of traveling wave ion mobility quadrupole time-of-flight (ToF) mass spectrometry for plasma metabolomics. Plasma metabolite profiles of obese Zucker fa/fa rats were obtained after the administration of different oral doses of Xanthohumol; a hop-derived dietary supplement. Liquid chromatography coupled data independent tandem mass spectrometry (LC-MSE) and LC-ion mobility spectrometry (IMS)-MSE acquisitions were conducted in both positive and negative modes using a Synapt G2 High Definition Mass Spectrometry (HDMS) instrument. This method provides identification of metabolite classes in rat plasma using parallel alternating low energy and high energy collision spectral acquisition modes. Data sets were analyzed using pattern recognition methods. Statistically significant (p < 0.05 and fold change (FC) threshold > 1.5) features were selected to identify the up-/down-regulated metabolite classes. Ion mobility data visualized using drift scope software provided a graphical read-out of differences in metabolite classes. Full article
(This article belongs to the Special Issue Response to Environment and Stress Metabolism)
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Review

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Open AccessReview Regulation Systems of Bacteria such as Escherichia coli in Response to Nutrient Limitation and Environmental Stresses
Metabolites 2014, 4(1), 1-35; doi:10.3390/metabo4010001
Received: 9 September 2013 / Revised: 18 November 2013 / Accepted: 6 December 2013 / Published: 30 December 2013
Cited by 21 | PDF Full-text (1828 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An overview was made to understand the regulation system of a bacterial cell such as Escherichia coli in response to nutrient limitation such as carbon, nitrogen, phosphate, sulfur, ion sources, and environmental stresses such as oxidative stress, acid shock, heat shock, and solvent
[...] Read more.
An overview was made to understand the regulation system of a bacterial cell such as Escherichia coli in response to nutrient limitation such as carbon, nitrogen, phosphate, sulfur, ion sources, and environmental stresses such as oxidative stress, acid shock, heat shock, and solvent stresses. It is quite important to understand how the cell detects environmental signals, integrate such information, and how the cell system is regulated. As for catabolite regulation, F1,6B P (FDP), PEP, and PYR play important roles in enzyme level regulation together with transcriptional regulation by such transcription factors as Cra, Fis, CsrA, and cAMP-Crp. αKG plays an important role in the coordinated control between carbon (C)- and nitrogen (N)-limitations, where αKG inhibits enzyme I (EI) of phosphotransferase system (PTS), thus regulating the glucose uptake rate in accordance with N level. As such, multiple regulation systems are co-ordinated for the cell synthesis and energy generation against nutrient limitations and environmental stresses. As for oxidative stress, the TCA cycle both generates and scavenges the reactive oxygen species (ROSs), where NADPH produced at ICDH and the oxidative pentose phosphate pathways play an important role in coping with oxidative stress. Solvent resistant mechanism was also considered for the stresses caused by biofuels and biochemicals production in the cell. Full article
(This article belongs to the Special Issue Response to Environment and Stress Metabolism)

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