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Impaired energy metabolism of the taurine-deficient heart

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Abstract

Taurine is a β-amino acid found in high concentrations in excitable tissues, including the heart. A significant reduction in myocardial taurine content leads to the development of a unique dilated, atrophic cardiomyopathy. One of the major functions of taurine in the heart is the regulation of the respiratory chain. Hence, we tested the hypothesis that taurine deficiency-mediated defects in respiratory chain function lead to impaired energy metabolism and reduced ATP generation. We found that while the rate of glycolysis was significantly enhanced in the taurine-deficient heart, glucose oxidation was diminished. The major site of reduced glucose oxidation was pyruvate dehydrogenase, an enzyme whose activity is reduced by the increase in the NADH/NAD+ ratio and by decreased availability of pyruvate for oxidation to acetyl CoA and changes in [Mg2+]i. Also diminished in the taurine-deficient heart was the oxidation of two other precursors of acetyl CoA, endogenous fatty acids and exogenous acetate. In the taurine-deficient heart, impaired citric acid cycle activity decreased both acetate oxidation and endogenous fatty acid oxidation, but reductions in the activity of the mitochondrial transporter, carnitine palmitoyl transferase, appeared to also contribute to the reduction in fatty acid oxidation. These changes diminished the rate of ATP production, causing a decline in the phosphocreatine/ATP ratio, a sign of reduced energy status. The findings support the hypothesis that the taurine-deficient heart is energy starved primarily because of impaired respiratory chain function, an increase in the NADH/NAD+ ratio and diminished long chain fatty acid uptake by the mitochondria. The results suggest that improved energy metabolism contributes to the beneficial effect of taurine therapy in patients suffering from heart failure.

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Acknowledgments

This work was supported by grants from Uehara Memorial Foundation and the American Heart Association.

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Authors and Affiliations

  1. Department of Pharmacology, University of South Alabama College of Medicine, Mobile, AL, 36688, USA

    Stephen W. Schaffer, Kayoko Shimada-Takaura & Chian Ju Jong

  2. School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan

    Takashi Ito

  3. Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

    Kyoko Takahashi

Authors
  1. Stephen W. Schaffer
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  2. Kayoko Shimada-Takaura
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  3. Chian Ju Jong
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  4. Takashi Ito
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  5. Kyoko Takahashi
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Correspondence to Stephen W. Schaffer.

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Conflict of interest

Stephen Schaffer serves as a consultant of Red Bull. None of the other authors have any conflict of interest.

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Schaffer, S.W., Shimada-Takaura, K., Jong, C.J. et al. Impaired energy metabolism of the taurine-deficient heart. Amino Acids 48, 549–558 (2016). https://doi.org/10.1007/s00726-015-2110-2

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  • DOI: https://doi.org/10.1007/s00726-015-2110-2

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