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Substrate Competition Studies Demonstrate Oxidative Metabolism of Glucose, Glutamate, Glutamine, Lactate and 3-Hydroxybutyrate in Cortical Astrocytes from Rat Brain

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Abstract

It is well established that astrocytes can utilize many substrates to support oxidative energy metabolism; however, use of energy substrates in the presence of other substrates, as would occur in vivo, has not been systematically evaluated. Substrate competition studies were used to determine changes in the rates of 14CO2 production since little is known about the interaction of energy substrates in astrocytes. The rates of 14CO2 production from 1 mM D-[6-14C]glucose, l-[U-14C]glutamate, l-[U-14C]glutamine, d-3-hydroxy[3-14C]butyrate, l-[U-14C]lactate and l-[U-14C]malate by primary cultures of astrocytes from rat brain were determined to be 1.17 ± 0.19, 85.30 ± 12.25, 28.04 ± 2.84, 13.55 ± 4.56, 14.84 ± 2.40 and 5.20 ± 1.20 nmol/h/mg protein (mean ± SEM), respectively. The rate of 14CO2 production from glutamate oxidation was higher than that of the other substrates Addition of unlabeled glutamate significantly decreased the rates of 14CO2 production from all other substrates studied; however, glutamate oxidation was not altered by the addition of any of the other substrates. The rate of 14CO2 production of glutamine was decreased by glutamate, but not altered by other substrates. The rate of 14CO2 production from glucose was significantly decreased by the addition of unlabeled glutamate, glutamine or lactate, but not by 3-hydroxybutyrate or malate. Addition of unlabeled glucose did not significantly alter the 14CO2 production from any other substrate. 14CO2 production from lactate was decreased by the addition of unlabeled glutamine or glutamate and increased by addition of malate. The 14CO2 production from malate was decreased by the addition of unlabeled glutamate or lactate, but was not altered by the other substrates. The substrate utilization for oxidative energy metabolism in astrocytes is very different than the profile previously reported for synaptic terminals. These studies demonstrate the potential use of multiple substrates including glucose, glutamate, glutamine, lactate and 3-hydroxybutyrate as energy substrates for astrocytes. The data also provide evidence of interactions of substrates and multiple compartments of TCA cycle activity in cultured astrocytes.

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Acknowledgments

This work was supported in part by NIH grant HD16596. The technical assistance of Irene Hopkins and Joseph Stevenson is gratefully acknowledged for performing these studies. I thank Dr. Leif Hertz for his insightful comments and feedback regarding this manuscript and his pioneering work in the field of brain energy metabolism.

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  1. Departments of Pediatrics and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA

    Mary C. McKenna

  2. Department of Pediatrics, University of Maryland School of Medicine, 655 W. Baltimore Street, Room 13-019 BRB, Baltimore, MD, 21201, USA

    Mary C. McKenna

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  1. Mary C. McKenna
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Correspondence to Mary C. McKenna.

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Special Issue: In Honor of Leif Hertz.

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McKenna, M.C. Substrate Competition Studies Demonstrate Oxidative Metabolism of Glucose, Glutamate, Glutamine, Lactate and 3-Hydroxybutyrate in Cortical Astrocytes from Rat Brain. Neurochem Res 37, 2613–2626 (2012). https://doi.org/10.1007/s11064-012-0901-3

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  • DOI: https://doi.org/10.1007/s11064-012-0901-3

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