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Isotopic Tracers for the Measurement of Metabolic Flux Rates

  • Carine BeysenEmail author
  • Thomas E. Angel
  • Marc K. Hellerstein
  • Scott M. Turner
Chapter

Abstract

Human metabolism is composed of complex networks, and objective, reliable measures (biomarkers) are needed to guide drug developers, disease researchers and clinicians toward safe and efficacious outcomes. The combination of stable isotope labeling with sensitive mass spectrometric analytic techniques is providing increasingly important tools for drug development and clinical studies. The use of stable isotopes allows the measurement of fluxes through metabolic pathways in vivo and provides information about what is newly produced and removed within a biological system and how rapidly molecules are being synthesized and degraded in disease physiology or response to treatment. This chapter describes select examples of applications for in vivo assessment of lipid, glucose, and protein metabolic flux. The approaches described use deuterated water and other stable isotope-labeled tracers that can be used effectively in early clinical research studies to study disease pathology and drug efficacy.

Keywords

Lipid metabolism Glucose metabolism Lipoprotein metabolism Protein synthesis In vivo Metabolic flux Isotope tracer Mass isotopomer distribution analysis (MIDA) Liver Muscle Adipose Translational Biomarker De novo lipogenesis Cell proliferation Endogenous glucose production Gluconeogenesis Glycogenolysis Glucose absorption Glycolysis Deuterated water GC/MS LC-MS/MS Nonalcoholic fatty liver disease (NAFLD) Nonalcoholic steatohepatitis (NASH) 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Carine Beysen
    • 1
    Email author
  • Thomas E. Angel
    • 2
  • Marc K. Hellerstein
    • 3
  • Scott M. Turner
    • 4
  1. 1.ProScientoChula VistaUSA
  2. 2.GlaxoSmithKlineKing of PrussiaUSA
  3. 3.University of California BerkeleyBerkeleyUSA
  4. 4.Pliant TherapeuticsSouth San FranciscoUSA

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