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Effects of branched-chain amino acids on muscles under hyperammonemic conditions

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Abstract

The aim was to determine the effects of enhanced availability of branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) on ammonia detoxification to glutamine (GLN) and protein metabolism in two types of skeletal muscle under hyperammonemic conditions. Isolated soleus (SOL, slow-twitch) and extensor digitorum longus (EDL, fast-twitch) muscles from the left leg of white rats were incubated in a medium with 1 mM ammonia (NH3 group), BCAAs at four times the concentration of the controls (BCAA group) or high levels of both ammonia and BCAA (NH3 + BCAA group). The muscles from the right leg were incubated in basal medium and served as paired controls. L-[1-14C]leucine was used to estimate protein synthesis and leucine oxidation, and 3-methylhistidine release was used to evaluate myofibrillar protein breakdown. We observed decreased protein synthesis and glutamate and α-ketoglutarate (α-KG) levels and increased leucine oxidation, GLN levels, and GLN release into medium in muscles in NH3 group. Increased leucine oxidation, release of branched-chain keto acids and GLN into incubation medium, and protein synthesis in EDL were observed in muscles in the BCAA group. The addition of BCAAs to medium eliminated the adverse effects of ammonia on protein synthesis and adjusted the decrease in α-KG found in the NH3 group. We conclude that (i) high levels of ammonia impair protein synthesis, activate BCAA catabolism, enhance GLN synthesis, and decrease glutamate and α-KG levels and (ii) increased BCAA availability enhances GLN release from muscles and attenuates the adverse effects of ammonia on protein synthesis and decrease in α-KG.

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Abbreviations

ALA:

Alanine

BCAAs:

Branched-chain amino acids

BCKA:

Branched-chain keto acids

EDL:

Musculus extensor digitorum longus

GLN:

Glutamine

GLU:

Glutamate

ILE:

Isoleucine

KIC:

α-Ketoisocaproate (ketoleucine)

KIV:

α-Ketoisovalerate (ketovaline)

KMV:

α-Keto-β-methylvalerate (ketoisoleucine)

LEU:

Leucine

SOL:

Musculus soleus

TCA cycle:

Tricarboxylic acid cycle

VAL:

Valine

α-KG:

α-Ketoglutarate

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Acknowledgements

The authors wish to thank R. Fingrova, D. Jezkova, and K. Sildbergerova for their technical assistance.

Funding

This project was supported by the PROGRES Q40/02 program.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03, Hradec Kralove, Czech Republic

    Milan Holeček & Melita Vodeničarovová

Authors
  1. Milan Holeček
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  2. Melita Vodeničarovová
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Contributions

MH outlined the experiments, performed the statistical analysis, interpreted the experimental results, and prepared the manuscript. MV was involved in the data acquisition and the data interpretation. Both authors read and approved the final manuscript.

Corresponding author

Correspondence to Milan Holeček.

Ethics declarations

All procedures involving animal manipulation were performed in accordance with guidelines set by the Institutional Animal Care and Use Committee of Charles University. The Animal Care and Use Committee of Charles University, Faculty of Medicine in Hradec Kralove, specifically approved this study (license no.144879/2011-MZE-17214).

Competing interest

The authors declare that they have no competing interests.

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Holeček, M., Vodeničarovová, M. Effects of branched-chain amino acids on muscles under hyperammonemic conditions. J Physiol Biochem 74, 523–530 (2018). https://doi.org/10.1007/s13105-018-0646-9

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  • DOI: https://doi.org/10.1007/s13105-018-0646-9

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