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  • Pam3CSK4 br Schulz KF Altman DG

    2020-07-28


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    8 GASTROINTESTINAL ENDOSCOPY Volume -, No. - : 2019 www.giejournal.org
    Ikehara et al
    Learning effect after e-learning training in endoscopic diagnosis
    SUPPLEMENTARY TABLE 1. Diagnostic accuracy for lesions with WOS finding (WOS-positive) in the answers of 365 participants
    Correct answer Incorrect answer Accuracy (%) P value
    WOS, White opaque substance.
    SUPPLEMENTARY TABLE 2. Diagnostic accuracy for lesions without WOS finding (WOS-negative) in the result of 365 raters
    Correct answer Incorrect answer Accuracy (%) P value
    WOS, White opaque substance.
    Contents lists available at ScienceDirect
    Analytical Biochemistry
    journal homepage: www.elsevier.com/locate/yabio
    Analysis of glucose-derived Pam3CSK4 involved in one-carbon and cancer T metabolism by stable-isotope tracing gas chromatography mass spectrometry
    Mark L. Sowersa,b, Jason Herringa, William Zhanga, Hui Tanga, Yang Ouc, Wei Guc, Kangling Zhanga,* a Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA b MD-PhD Combined Degree Program, University of Texas Medical Branch, Galveston, TX, 77555, USA c Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, 10032, USA
    Keywords:
    Cancer metabolism
    One carbon metabolism
    Glucose metabolism
    Warburg effect
    Serine metabolism
    GC/MS
    Isotope traing mass spectrometry 
    A major hallmark of cancer is a perturbed metabolism resulting in high demand for various metabolites, glucose being the most well studied. While glucose can be converted into pyruvate for ATP production, the serine synthesis pathway (SSP) can divert glucose to generate serine, glycine, and methionine. In the process, the carbon unit from serine is incorporated into the one-carbon pool which makes methionine and maintains S-adenosylmethionine levels, which are needed to maintain the epigenetic landscape and ultimately controlling what genes are available for transcription. Alternatively, the carbon unit can be used for purine and thymidylate synthesis. We present here an approach to follow the flux through this pathway in cultured human cells using stable isotope enriched glucose and gas chromatography mass spectrometry analysis of serine, glycine, and methionine. We demonstrate that in three different cell lines this pathway contributes only 1–2% of total in-tracellular methionine. This suggests under high extracellular methionine conditions, the predominance of carbon units from this pathway are used to synthesize nucleic acids.
    1. Introduction
    Human tumors have a distinct metabolism, most notably a pre-dilection for glucose. However, the utility and fate of those carbon atoms remains incompletely understood. Normally in the absence of oxygen glucose is converted to pyruvate and ultimately lactate. This generates only a fraction of the ATP possible by aerobic cellular re-spiration, which requires oxygen as the final electron donor. While anaerobic glycolysis can be accomplished by most cells, cancer cells have the unusual property of converting much of their glucose to lac-tate, even in the presence of oxygen. The process is termed aerobic glycolysis. Aerobic glycolysis underlies the Warburg effect, long re-cognized as a defining property of many cancers [1]. Much of the glucose can of course be used as a source of ATP, albeit less efficiently than oxidative phosphorylation which yield 2 ATP and 36 ATP per equivalent of glucose, respectively. But, there may be some benefits despite the trade-off, such as a higher rate of ATP generation on de-mand [1,2].