Tricarboxylic acid-cycle metabolism in brain. Effect of fluoroacetate and fluorocitrate on the labelling of glutamate aspartate, glutamine and γ-amino butyrate |
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Authors: | D D Clarke W J Nicklas and S Berl |
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Institution: | Department of Chemistry, Fordham University, Bronx, N.Y. 10458, U.S.A.;Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, N.Y. 10032, U.S.A. |
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Abstract: | 1. The effect of fluoroacetate and fluorocitrate on the compartmentation of the glutamate-glutamine system was studied in brain slices with l-U-(14)C]glutamate, l-U-(14)C]aspartate, 1-(14)C]acetate and gamma-amino1-(14)C]butyrate as precursors and in homogenates of brain tissue with 1-(14)C]acetate. The effect of fluoroacetate was also studied in vivo in mouse brain with 1-(14)C]acetate as precursor. 2. Fluoroacetate and fluorocitrate inhibit the labelling of glutamine from all precursors but affect the labelling of glutamate to a much lesser extent. This effect is not due to inhibition of glutamine synthetase. It is interpreted as being due to selective inhibition of the metabolism of a small pool of glutamate that preferentially labels glutamine. |
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