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Twenty-seven Years of Cerebral Pyruvate Recycling

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Abstract

Cerebral pyruvate recycling is a metabolic pathway deriving carbon skeletons and reducing equivalents from mitochondrial oxaloacetate and malate, to the synthesis of mitochondrial and cytosolic pyruvate, lactate and alanine. The pathway allows both, to provide the tricarboxylic acid cycle with pyruvate molecules produced from alternative substrates to glucose and, to generate reducing equivalents necessary for the operation of NADPH requiring processes. At the cellular level, pyruvate recycling involves the activity of malic enzyme, or the combined activities of phosphoenolpyruvate carboxykinase and pyruvate kinase, as well as of those transporters of the inner mitochondrial membrane exchanging the corresponding intermediates. Its cellular localization between the neuronal or astrocytic compartments of the in vivo brain has been controversial, with evidences favoring either a primarily neuronal or glial localizations, more recently accepted to occur in both environments. This review provides a brief history on the detection and characterization of the pathway, its relations with the early developments of cerebral high resolution 13C NMR, and its potential neuroprotective functions under hypoglycemic conditions or ischemic redox stress.

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Abbreviations

α-KG:

α-ketoglutarate

Lac:

Lactate

LDH:

Lactate dehydrogenase

NMR:

Nuclear magnetic resonance

ME:

Malic enzyme (E.C. 1.1.1.40)

MRS:

Magnetic resonance spectroscopy

Mal:

Malate

OAA:

Oxaloacetate

PDH:

Pyruvate dehydrogenase (E.C. 1.2.4.1., 1.8.1.4., 2.3.4.12)

PEPCK:

Phosphoenolpyruvate carboxykinase (E.C. 4.1.1.1.32)

PK:

Pyruvate kinase (E.C. 2.7.1.40)

TCA:

Tricarboxylic acid cycle

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Acknowledgements

The author is deeply indebted to many generations of students, post-docs and technicians that contributed time and effort to the experiments outlined above. The contribution of Prof. Paloma Ballesteros UNED and Mr. Javier Pérez CSIC providing careful reading of the manuscript and professional drafting of the illustrations is gratefully acknowledged.

Funding

This work was supported in part by Grants SAF2014-53739-R and S2010/BMD-2349 to SC. Funding sources were not involved in the design of the study, in the collection, analysis and interpretation of data, in the writing of the report nor in the decision to submit the article for publication.

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Authors and Affiliations

  1. Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC/UAM, c/ Arturo Duperier 4, 28029, Madrid, Spain

    Sebastián Cerdán

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  1. Sebastián Cerdán
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Correspondence to Sebastián Cerdán.

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Special Issue: Dedicated to Prof. Ursula Sonnewald.

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Cerdán, S. Twenty-seven Years of Cerebral Pyruvate Recycling. Neurochem Res 42, 1621–1628 (2017). https://doi.org/10.1007/s11064-017-2173-4

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  • DOI: https://doi.org/10.1007/s11064-017-2173-4

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