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Insights on Lactate Metabolism in Skeletal Muscle Based on 13C Dynamic Nuclear Polarization Studies

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Dynamic Hyperpolarized Nuclear Magnetic Resonance

Part of the book series: Handbook of Modern Biophysics ((HBBT))

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Abstract

Despite the textbook pronouncements about muscle lactate (lac) as a glycolytic end-product, which many use to characterize a hypoxia threshold, and as a precursor for recycling in liver, recent studies have begun to challenge these edicts. Indeed, experiment observations have detected lac formation under aerobic conditions and lac shuttling between muscle fibers and within the myocyte as a metabolic precursor. The observations have spawned novel hypothesis to explain aerobic lac formation as part of a dynamic glycogen shunt during a muscle twitch. Since nuclear magnetic resonance (NMR) has detected a large energy fluctuation during each contraction, the cell must dynamically restore glycogen in order to sustain any extended period of contractions. Because of enhanced signal sensitivity to measure kinetics in seconds, dynamic nuclear polarization (DNP) NMR experiments can test key elements of these models. Both the glycogen shunt and intracellular lac shuttle models require rapid mobilization and utilization of lac. If lac cannot mobilize rapidly, then the results invalidate immediately the hypotheses in both models. Can muscle then use and mobilize lac? Indeed, the DNP experiment results show rapid lac utilization, which appears to support the validity of the glycogen shunt and lac shuttle model.

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Further Reading

  • Brooks, G.A.: Cell-cell and intracellular lactate shuttles. J. Physiol. 587, 5591–5600 (2009)

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  • Chung, Y., Sharman, R., Carlsen, R., Unger, S.W., Larson, D., Jue, T.: Metabolic fluctuation during a muscle contraction cycle. Am. J. Phys. Cell Physiol. 274, C846–CC52 (1998)

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  • Park, J.M., Josan, S., Jang, T., Merchant, M., Yen, Y.F., et al.: Metabolite kinetics in C6 rat glioma model using magnetic resonance spectroscopic imaging of hyperpolarized [1-(13)C]pyruvate. Magn. Reson. Med. 68, 1886–1893 (2012)

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  • Shulman, R.G., Rothman, D.L.: The “glycogen shunt” in exercising muscle: a role for glycogen in muscle energetics and fatigue. Proc. Natl. Acad. Sci. U. S. A. 98, 457–461 (2001)

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Acknowledgments

We acknowledge funding support from NIH (P41 EB015891 and R01 NS107409-01A1), the Welch Foundation (I-2009-20190330), and France Berkeley Fund, California Department of Public Health 18-10923.

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Authors and Affiliations

  1. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Jae Mo Park

  2. Biochemistry and Molecular Medicine, University of California Davis, Davis, CA, USA

    Thomas Jue

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Correspondence to Thomas Jue .

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Editors and Affiliations

  1. Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, CA, USA

    Thomas Jue

  2. Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, Baltimore, MD, USA

    Dirk Mayer

Problems

Problems

  1. 1.

    How does the glycogen shunt hypothesis explain the formation of lactate during exercise, when the cell has not crossed any hypoxia threshold?

  2. 2.

    Do you expect any changes of metabolic products in skeletal muscle after exercise when hyperpolarized either [1-13C]lactate or [2-13C]pyruvate is injected?

  3. 3.

    From hyperpolarized [2-13C]pyruvate, no TCA intermediates are observed in the spectra although glutamate was detected. Can you explain why? On the other hand, a large acetyl-carnitine peak was shown. What does it imply?

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Park, J.M., Jue, T. (2021). Insights on Lactate Metabolism in Skeletal Muscle Based on 13C Dynamic Nuclear Polarization Studies. In: Jue, T., Mayer, D. (eds) Dynamic Hyperpolarized Nuclear Magnetic Resonance. Handbook of Modern Biophysics. Springer, Cham. https://doi.org/10.1007/978-3-030-55043-1_10

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