Tracking leucine metabolism in prostate cancer cells via $^{\mathrm{13}}$C NMR spectroscopy

ORAL

Abstract

Nuclear magnetic resonance (NMR) spectroscopy is relatively insensitive due to the weak magnetic moments of nuclei, especially those with low gyromagnetic ratio ($\gamma )$ such as $^{\mathrm{13}}$C ($\gamma =$ 10.705 MHz/T). Fortunately, a technique known as dynamic nuclear polarization (DNP) enhances the NMR signals by transferring the much higher electron ($\gamma =$ 28,000 MHz/T) polarization to nuclei. Furthermore, the invention of dissolution DNP in 2003 has expanded DNP's large signal enhancement (more than 10,000-fold) to the biomedical realm. Significantly, dissolution DNP allows real-time tracking of metabolism via labeling the relevant substrate with $^{\mathrm{13}}$C. This study examined the real-time prostate cancer cell enzyme kinetics involved in the metabolism of [1-$^{\mathrm{13}}$C] alpha-ketoisocaproate [$\alpha $-KIC] into [1-$^{\mathrm{13}}$C] leucine and vice versa. Results of \textit{in vitro} conventional 13C NMR of cell extracts and hyperpolarized 13C NMR of living prostate cancers cells will be discussed in the context of biochemical kinetics and possible diagnostic application.

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Authors

  • Christopher Parish

    University of Texas at Dallas, The University of Texas at Dallas

  • Qiye Zheng

    Santa Fe Institute, Baylor University, University of Texas at Dallas, Department of Chemistry, The University of Texas at Austin, Jozef Stefan Institute, Texas A&M University-Commerce, Commerce, Texas 75429, Cyclotron Institute, Texas A&M University, College Station, Texas 77843, Texas A&M University, Department of Physics, Texas State University, Department of Physics, Baylor University, University of Texas at El Paso, Univ of Texas, El Paso, University of Science and Technology of China, The University of Texas at Dallas, Faculty, None, Southwestern University, Texas State University, Texas A&M University - Commerce, UT Southwestern Medical Center, National High Magnetic Field Laboratory, The Cyclotron Institute at Texas A&M University, Department of Biological Sciences, Texas State Univ-San Marcos, The University of Texas at Dallas, Richardson, Texas 75080, King Abdullah University of Science and Technology, Univ of Texas, Dallas, N.Chiao Tung U., UT Dallas, Inorganic Chemistry and Catalysis Group, Utrecht University, Electrical & Computer Engineering, Baylor University, Department of Materials Science and NanoEngineering, Rice University, University of Texas at Arlington, University of Chicago, The University of Mississippi, Astronomical Observatory, Warsaw University, Nicolaus Copernicus Astronomical Centre, Polish Academy of Sciences, Rochester Institute of Technology, California Institute of Technology, University of Houston, NASA-GSFC and UMBC, MD, Virginia Tech, VA, Texas Christian University, The University of Texas at San Antonio, Department of Physics, Teivecca Nazarene University, Weatherford College, Air Force Research Laboratory, Sensors Directorate, WPAFB, OH, USA, Air Force Research Laboratory, Directed Energy Directorate, KAFB, NM, US, Department of Physics & Astronomy, University of Texas at San Antonio TX, USA, University of Arizona, University of North Carolina at Chapel Hill, Stanford University, Harvard Center for Astrophysics, Texas A\&M University, UTSW, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, Boston College, Chestnut Hill, Massachusetts 02467, Naval Research Laboratory, Washington, D.C. 20375

  • Qiye Zheng

    Santa Fe Institute, Baylor University, University of Texas at Dallas, Department of Chemistry, The University of Texas at Austin, Jozef Stefan Institute, Texas A&M University-Commerce, Commerce, Texas 75429, Cyclotron Institute, Texas A&M University, College Station, Texas 77843, Texas A&M University, Department of Physics, Texas State University, Department of Physics, Baylor University, University of Texas at El Paso, Univ of Texas, El Paso, University of Science and Technology of China, The University of Texas at Dallas, Faculty, None, Southwestern University, Texas State University, Texas A&M University - Commerce, UT Southwestern Medical Center, National High Magnetic Field Laboratory, The Cyclotron Institute at Texas A&M University, Department of Biological Sciences, Texas State Univ-San Marcos, The University of Texas at Dallas, Richardson, Texas 75080, King Abdullah University of Science and Technology, Univ of Texas, Dallas, N.Chiao Tung U., UT Dallas, Inorganic Chemistry and Catalysis Group, Utrecht University, Electrical & Computer Engineering, Baylor University, Department of Materials Science and NanoEngineering, Rice University, University of Texas at Arlington, University of Chicago, The University of Mississippi, Astronomical Observatory, Warsaw University, Nicolaus Copernicus Astronomical Centre, Polish Academy of Sciences, Rochester Institute of Technology, California Institute of Technology, University of Houston, NASA-GSFC and UMBC, MD, Virginia Tech, VA, Texas Christian University, The University of Texas at San Antonio, Department of Physics, Teivecca Nazarene University, Weatherford College, Air Force Research Laboratory, Sensors Directorate, WPAFB, OH, USA, Air Force Research Laboratory, Directed Energy Directorate, KAFB, NM, US, Department of Physics & Astronomy, University of Texas at San Antonio TX, USA, University of Arizona, University of North Carolina at Chapel Hill, Stanford University, Harvard Center for Astrophysics, Texas A\&M University, UTSW, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, Boston College, Chestnut Hill, Massachusetts 02467, Naval Research Laboratory, Washington, D.C. 20375

  • Qiye Zheng

    Santa Fe Institute, Baylor University, University of Texas at Dallas, Department of Chemistry, The University of Texas at Austin, Jozef Stefan Institute, Texas A&M University-Commerce, Commerce, Texas 75429, Cyclotron Institute, Texas A&M University, College Station, Texas 77843, Texas A&M University, Department of Physics, Texas State University, Department of Physics, Baylor University, University of Texas at El Paso, Univ of Texas, El Paso, University of Science and Technology of China, The University of Texas at Dallas, Faculty, None, Southwestern University, Texas State University, Texas A&M University - Commerce, UT Southwestern Medical Center, National High Magnetic Field Laboratory, The Cyclotron Institute at Texas A&M University, Department of Biological Sciences, Texas State Univ-San Marcos, The University of Texas at Dallas, Richardson, Texas 75080, King Abdullah University of Science and Technology, Univ of Texas, Dallas, N.Chiao Tung U., UT Dallas, Inorganic Chemistry and Catalysis Group, Utrecht University, Electrical & Computer Engineering, Baylor University, Department of Materials Science and NanoEngineering, Rice University, University of Texas at Arlington, University of Chicago, The University of Mississippi, Astronomical Observatory, Warsaw University, Nicolaus Copernicus Astronomical Centre, Polish Academy of Sciences, Rochester Institute of Technology, California Institute of Technology, University of Houston, NASA-GSFC and UMBC, MD, Virginia Tech, VA, Texas Christian University, The University of Texas at San Antonio, Department of Physics, Teivecca Nazarene University, Weatherford College, Air Force Research Laboratory, Sensors Directorate, WPAFB, OH, USA, Air Force Research Laboratory, Directed Energy Directorate, KAFB, NM, US, Department of Physics & Astronomy, University of Texas at San Antonio TX, USA, University of Arizona, University of North Carolina at Chapel Hill, Stanford University, Harvard Center for Astrophysics, Texas A\&M University, UTSW, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, Boston College, Chestnut Hill, Massachusetts 02467, Naval Research Laboratory, Washington, D.C. 20375

  • Qiye Zheng

    Santa Fe Institute, Baylor University, University of Texas at Dallas, Department of Chemistry, The University of Texas at Austin, Jozef Stefan Institute, Texas A&M University-Commerce, Commerce, Texas 75429, Cyclotron Institute, Texas A&M University, College Station, Texas 77843, Texas A&M University, Department of Physics, Texas State University, Department of Physics, Baylor University, University of Texas at El Paso, Univ of Texas, El Paso, University of Science and Technology of China, The University of Texas at Dallas, Faculty, None, Southwestern University, Texas State University, Texas A&M University - Commerce, UT Southwestern Medical Center, National High Magnetic Field Laboratory, The Cyclotron Institute at Texas A&M University, Department of Biological Sciences, Texas State Univ-San Marcos, The University of Texas at Dallas, Richardson, Texas 75080, King Abdullah University of Science and Technology, Univ of Texas, Dallas, N.Chiao Tung U., UT Dallas, Inorganic Chemistry and Catalysis Group, Utrecht University, Electrical & Computer Engineering, Baylor University, Department of Materials Science and NanoEngineering, Rice University, University of Texas at Arlington, University of Chicago, The University of Mississippi, Astronomical Observatory, Warsaw University, Nicolaus Copernicus Astronomical Centre, Polish Academy of Sciences, Rochester Institute of Technology, California Institute of Technology, University of Houston, NASA-GSFC and UMBC, MD, Virginia Tech, VA, Texas Christian University, The University of Texas at San Antonio, Department of Physics, Teivecca Nazarene University, Weatherford College, Air Force Research Laboratory, Sensors Directorate, WPAFB, OH, USA, Air Force Research Laboratory, Directed Energy Directorate, KAFB, NM, US, Department of Physics & Astronomy, University of Texas at San Antonio TX, USA, University of Arizona, University of North Carolina at Chapel Hill, Stanford University, Harvard Center for Astrophysics, Texas A\&M University, UTSW, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, Boston College, Chestnut Hill, Massachusetts 02467, Naval Research Laboratory, Washington, D.C. 20375