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Ischemia promotes acyl-CoAs dephosphorylation and propionyl-CoA accumulation

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Abstract

Introduction

Our untargeted metabolic data unveiled that Acyl-CoAs undergo dephosphorylation, however little is known about these novel metabolites and their physiology/pathology relevance.

Objectives

To understand the relationship between acyl-CoAs dephosphorylation and energy status as implied in our previous work, we seek to investigate how ischemia (energy depletion) triggers metabolic changes, specifically acyl-CoAs dephosphorylation in this work.

Methods

Rat hearts were isolated and perfused in Langendorff mode for 15 min followed by 0, 5, 15, and 30 minutes of global ischemia. The heart tissues were harvested for metabolic analysis.

Results

As expected, ATP and phosphocreatine were significantly decreased during ischemia. Most short- and medium-chain acyl-CoAs progressively increased with ischemic time from 0 to 15 min, whereas a 30-minute ischemia did not lead to further change. Unlike other acyl-CoAs, propionyl-CoA accumulated progressively in the hearts that underwent ischemia from 0 to 30 min. Progressive dephosphorylation occurred to all assayed acyl-CoAs and free CoA regardless their level changes during the ischemia.

Conclusion

The present work further confirms that dephosphorylation of acyl-CoAs is an energy-dependent process and how this dephosphorylation is mediated warrants further investigations. It is plausible that dephosphorylation of acyl-CoAs and limited anaplerosis are involved in ischemic injuries to heart. Further investigations are warranted to examine the mechanisms of acyl-CoA dephosphorylation and how the dephosphorylation is possibly involved in ischemic injuries.

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Acknowledgements

This publication was made possible by AHA award 12GRNT12050453 to G.F.Z.

Funding

This study was supported by American Heart Association (Grant No. 12GRNT12050453)

Author information

Author notes

  1. Jessica M. Berthiaume

    Present address: Inotiv Westminster, 7581 W 103rd Ave, Westminster, CO, 80021, USA

  2. Wentao He and Jessica M. Berthiaume have equally contributed to this work.

Authors and Affiliations

  1. Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University, Durham, NC, 27701, USA

    Wentao He & Guo-Fang Zhang

  2. Department of Physiology & Biophysics, Case Western Reserve University, Cleveland, OH, 44104, USA

    Jessica M. Berthiaume

  3. Merck & Co., Inc, 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA

    Stephen Previs

  4. Northeast Ohio Medical University, Rootstown, OH, 44272, USA

    Takhar Kasumov

  5. Department of Medicine, Division of Endocrinology, Metabolism Nutrition, Duke University Medical Center, Durham, NC, 27701, USA

    Guo-Fang Zhang

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  1. Wentao He
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Correspondence to Guo-Fang Zhang.

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S.F.P. is currently employed by and owns stock in Merck.

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He, W., Berthiaume, J.M., Previs, S. et al. Ischemia promotes acyl-CoAs dephosphorylation and propionyl-CoA accumulation. Metabolomics 19, 12 (2023). https://doi.org/10.1007/s11306-023-01975-2

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