Special Issue "Stable Isotope Guided Metabolomics"
Deadline for manuscript submissions: 15 September 2020.
Interests: stable isotope resolved metabolomics; method development; fluxomics; metabolic pathway activity; high-resolution mass spectrometry
The use of stable isotope-labeled compounds in studying metabolism and biological processes is widespread. The Special Issue of Metabolites, "Stable Isotope-Guided Metabolomics", will focus on cutting-edge and newly established metabolomics technologies and workflows that significantly benefit from the use of stable isotopically labeled compounds. This includes methodologies for in vitro and in vivo stable metabolite pathway tracing and flux analyses, as well as applications that improve quality, confidence, and validation of metabolomics analyses and aid in metabolite assignments and quantification. In this Special Issue, we aim to cover a variety of topics, including experimental design, workflows for the analysis of isotopically enriched data, statistical and computational approaches for data analysis and interpretation, and other important topics.
Dr. Pawel Lorkiewicz
Manuscript Submission Information
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. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind 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 monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
- stable isotopes
- flux analysis
- pathway tracing
- isotope labeling
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
A Comparative Study of Stable Isotope Tracing of Hepatic Metabolism Using [U-13C]Propionate and [U-13C]Glutamine
Mukundan Ragavan, Anthony Giacalone, Marc McLeod, Saleel Sripada, Clayton Olinger, Samira Ahmed, and Matthew E. Merritt
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611
Tracer based assessments of hepatic metabolism provide direct insight into metabolic turnover rates and can be essential for understanding the metabolic mechanism underlying various pathophysiologies. Different tracers including [U-13C]acetate and [U-13C]propionate have been used to probe oxidative capacity of the liver – each with its own strengths and drawbacks. We report the use of [U-13C]glutamine to assess hepatic citric acid cycle flux and gluconeogenesis in perfused mice livers using 2H and 13C NMR spectroscopy, and compare the results obtained with the [U-13C]propionate method. Two different concentrations of [U-13C]glutamine are assessed for the effect of concentration on endogenous glucose production. Overall, glutamine, even at the lower concentration of 100 µM, works well as a tracer and can report accurately on the TCA cycle flux and gluconeogenesis in perfused livers.
Capitalizing on chromatography to enhance the quantitation of 2H-labeling.
Stephen F. Previs, PhD and Daniel P. Downes, PhD
Department of Chemistry, Merck & Co., Inc., Kenilworth, NJ, USA; 2000 Galloping Hill Road, K15-MW111
Kenilworth, NJ 07033 USA
Takhar Kasumov, PhD
Assistant Professor of Pharmaceutical Sciences; Director of Mass Spectrometry Core, College of Pharmacy
Northeast Ohio Medical University, Rootstown, Ohio 44272
Abstract. Stable isotopes tracers can be used to quantify the activity of metabolic pathways. Specifically, 2H-water is quite versatile, enabling measures of carbohydrate, lipid, protein and nucleic acid kinetics. Although some applications require that one determine the total 2H-labeling of a given end-product, other applications rely on measures of positional labeling. Regardless of the study, one typically measures the isotope abundance following the administration of 2H-water and subtracts the natural background isotope abundance using a baseline sample (collected before 2H-water is administered). Since there are limits on how much 2H-water can be administered and since some metabolic processes may be slow, it is possible that one may be challenged with measuring small changes in the isotope profile. Herein, we will consider different analytical strategies to overcome problems surrounding the quantitation of small enrichments. The primary focus is to discuss how one can take advantage of chromatography in cases where low levels of 2H-labeling are expected; we compare the use of novel integration routines for GC-MS data acquisitions against the use of tandem mass spectrometry and/or high-resolution mass spectrometry, including isotope ratio mass spectrometry. Relatively simple changes in the data processing allow GC-q-MS measurements of 2H-labeling to approach the limits seen with alternative analytical methods.
New methods of determining lipid turnover via stable isotope resolved metabolomics using ultrahigh resolution MS and NMR
Richard M. Higashi, Woo-Young Wang, Teresa W-M Fan, Penghui Lin, Andrew N Lane.
Lipids comprise diverse classes of compounds that are important for the structure and properties of membranes, as high-energy fuel sources, and as signaling molecules. Therefore the turnover rates of these varied classes of lipids is fundamental to cellular function. However their enormous chemical diversity and dynamic range in cells makes detailed analysis very complex. Furthermore, although stable isotope tracers enable the determination of synthesis and degradation of complex lipids, the numbers of distinguishable molecules increase enormously, which exacerbates the problem. Here we report new developments in ultrahigh resolution tandem mass spectrometry for lipid identification and quantification, and the role of NMR analysis for assessing overall features of mixtures of complex lipids.
Areas to cover:
Lipid identification by ultrahigh resolution tandem MS with UVPD- and what this also reveals about lipid complexity
SIRM and intact lipids- metabolic subunits
NMR and tandem FT-MS leads to isotopomer and subunit labeling analysis
Global lipid properties and enrichments by NMR