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  • 1
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    Serine is a natural ligand and allosteric activator of pyruvate kinase M2 (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-10-16
    Description: Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation. Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of serine and glycine. Here we describe a new rheostat-like mechanistic relationship between PKM2 activity and serine biosynthesis. We show that serine can bind to and activate human PKM2, and that PKM2 activity in cells is reduced in response to serine deprivation. This reduction in PKM2 activity shifts cells to a fuel-efficient mode in which more pyruvate is diverted to the mitochondria and more glucose-derived carbon is channelled into serine biosynthesis to support cell proliferation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894725/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894725/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chaneton, Barbara -- Hillmann, Petra -- Zheng, Liang -- Martin, Agnes C L -- Maddocks, Oliver D K -- Chokkathukalam, Achuthanunni -- Coyle, Joseph E -- Jankevics, Andris -- Holding, Finn P -- Vousden, Karen H -- Frezza, Christian -- O'Reilly, Marc -- Gottlieb, Eyal -- A12477/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2012 Nov 15;491(7424):458-62. doi: 10.1038/nature11540. Epub 2012 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, Scotland, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23064226" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; Cell Proliferation ; Enzyme Activation/drug effects ; Enzyme Activators/pharmacology ; Glucose/metabolism ; Glycine/metabolism/pharmacology ; Humans ; *Ligands ; Pyruvate Kinase/genetics/*metabolism ; Pyruvic Acid/metabolism ; Recombinant Proteins/metabolism ; Serine/*metabolism/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    mzMatch-ISO: an R tool for the annotation and relative quantification of isotope-labelled mass spectrometry data (2013)
    Oxford University Press
    Details
    Publication Date: 2013-01-17
    Description: Motivation: Stable isotope - labelling experiments have recently gained increasing popularity in metabolomics studies, providing unique insights into the dynamics of metabolic fluxes, beyond the steady-state information gathered by routine mass spectrometry. However, most liquid chromatography–mass spectrometry data analysis software lacks features that enable automated annotation and relative quantification of labelled metabolite peaks. Here , we describe mzMatch–ISO, a new extension to the metabolomics analysis pipeline mzMatch.R. Results: Targeted and untargeted isotope profiling using mzMatch–ISO provides a convenient visual summary of the quality and quantity of labelling for every metabolite through four types of diagnostic plots that show (i) the chromatograms of the isotope peaks of each compound in each sample group; (ii) the ratio of mono-isotopic and labelled peaks indicating the fraction of labelling; (iii) the average peak area of mono - isotopic and labelled peaks in each sample group; and (iv) the trend in the relative amount of labelling in a predetermined isotopomer. To aid further statistical analyses, the values used for generating these plots are also provided as a tab - delimited file. We demonstrate the power and versatility of mzMatch–ISO by analysing a 13 C - labelled metabolome dataset from trypanosomal parasites. Availability: mzMatch.R and mzMatch–ISO are available free of charge from http://mzmatch.sourceforge.net and can be used on Linux and Windows platforms running the latest version of R. Contact: rainer.breitling@manchester.ac.uk . Supplementary information: Supplementary data are available at Bioinformatics online
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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