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Glial Metabolism of Isoleucine

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Abstract

Isoleucine, together with leucine and valine, constitutes the group of branched-chain amino acids (BCAAs). BCAAs are transported from the blood into the brain parenchyma, where they can serve several distinct functions. Since brain tissue is known to oxidatively metabolize BCAAs to CO2, they are considered as fuel material in brain energy metabolism. Also, in the case of leucine, cultured astrocytes have been reported to be able to completely oxidize BCAA. While the metabolism of leucine by astroglia-rich primary culture (APC) has already been studied in detail, the metabolic fates of isoleucine and valine in these cells remained to be identified. Therefore, in the present study an NMR analysis was performed of 13C-labelled metabolites generated in the catabolism of [U-13C]Ile by astrocytes and released by them into the incubation medium. APC potently removed isoleucine from the medium and metabolized it. The major isoleucine metabolites released from APC are 2-oxo-3-methylvalerate, 2-methylbutyrate, 3-hydroxy-2-methylbutyrate and propionate. To a lesser extent, APC generate and release also [2,3-13C]glutamine, [4,5-13C]glutamine and 13C-labelled isotopomers of lactate and citrate. These results show that APC can release into the extracellular milieu catabolites and several TCA cycle dependent metabolites resulting from the degradation of isoleucine.

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Acknowledgment

The authors should like to acknowledge some preliminary experiments carried out by Krešimir Mikić.

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Authors and Affiliations

  1. Interfaculty Institute for Biochemistry, University of Tuebingen, Hoppe-Seyler-Str. 4, 72076, Tuebingen, Germany

    Radovan Murín & Bernd Hamprecht

  2. Institute for Organic Chemistry, University of Bremen, Bremen, Germany

    Ghasem Mohammadi & Dieter Leibfritz

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  1. Radovan Murín
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  2. Ghasem Mohammadi
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  3. Dieter Leibfritz
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  4. Bernd Hamprecht
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Correspondence to Radovan Murín.

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Special issue article in honor of Dr. George DeVries.

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Murín, R., Mohammadi, G., Leibfritz, D. et al. Glial Metabolism of Isoleucine. Neurochem Res 34, 194–204 (2009). https://doi.org/10.1007/s11064-008-9840-4

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