Tricarboxylic acid-cycle metabolism in brain. Effect of fluoroacetate and fluorocitrate on the labelling of glutamate aspartate, glutamine and γ-amino butyrate
TLDR
Fluoroacetate and fluorocitrate inhibit thelabelling of glutamine from all precursors but affect the labelling of glutamate to a much lesser extent, interpreted as being due to selective inhibition of the metabolism of a small pool of glutamate that preferentially labels glutamine.Abstract:
1. The effect of fluoroacetate and fluorocitrate on the compartmentation of the glutamate–glutamine system was studied in brain slices with l-[U-14C]glutamate, l-[U-14C]aspartate, [1-14C]acetate and γ-amino[1-14C]butyrate as precursors and in homogenates of brain tissue with [1-14C]acetate. The effect of fluoroacetate was also studied in vivo in mouse brain with [1-14C]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.read more
Citations
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The metabolic fate of 13N-labeled ammonia in rat brain.
TL;DR: Analysis of 13N-metabolites indicated that ammonia entering the brain from the cerebrospinal fluid is also metabolized in a small glutamate pool, and emphasize the importance of the small pool glutamine synthetase as a metabolic trap for the detoxification of blood-borne and endogenously produced brain ammonia.
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The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain.
TL;DR: The glutamate‐glutamine cycle is not a stoichiometric cycle but rather an open pathway that interfaces with many other metabolic pathways to varying extents depending on cellular requirements and priorities.
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The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat.
TL;DR: A role for iNOS, expressed by glia, in mechanisms of hyperalgesia is shown, suggesting an unexplored avenue for the development of potential new and novel therapies for pain control.
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Cerebral metabolism of acetate and glucose studied by 13C-n.m.r. spectroscopy. A technique for investigating metabolic compartmentation in the brain.
TL;DR: The time courses of incorporation of 13C from 13C-labelled glucose or acetate into cerebral amino acids (glutamate, glutamine and 4-aminobutyrate) and lactate were monitored to provide the possibility of distinguishing differential effects of metabolic perturbations on the two pools simultaneously.
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An In Vivo Model for Studying Function of Brain Tissue Temporarily Devoid of Glial Cell Metabolism: The Use of Fluorocitrate
TL;DR: The use of microinjection of 1 nmol of fluorocitrate into the neostria‐tum of the rat to provide a model for studying transmitter amino acid metabolism in brain devoid of glial cell activity is discussed.
References
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Effects of Changes in Brain Metabolism on the Levels of Citric Acid Cycle Intermediates
TL;DR: Decreasing the metabolic flux with anesthetic agents resulted in each case in marked decreases in α-ketoglutarate, fumarate, and malate, whereas increasing the flux by hyperthermia resulted in increases in these same three substrates.
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Precursors in vivo of glutamate, aspartate and their derivatives of rat brain.
Robert M. O'Neal,Roger E. Koeppe +1 more
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The heterogeneity of rat brain mitochondria isolated on continuous sucrose gradients.
TL;DR: The distribution of a series of enzymes in the post‐nuclear supernatant of rat brain homogenates was investigated following continuous density‐gradient centrifugation, suggesting that brain mitochondria may be heterogeneous both in buoyant density and in their enzyme content.
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Subcellular Distribution of Pyruvate Carboxylase, Diphosphopyridine Nucleotide and Triphosphopyridine Nucleotide Isocitrate Dehydrogenases, and Malate Enzyme in Rat Brain
Leon Salganicoff,Roger E. Koeppe +1 more
TL;DR: Information concerning the nonuniform distribution of these enzymes in nerve endings, as compared with neuron plus glia, is presented and the relationship to models of compartmentation of amino acids and Krebs cycle intermediates in brain is considered.
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Compartmentation of citric acid cycle metabolism in brain: labelling of glutamate, glutamine, aspartate and gaba by several radioactive tracer metabolites.
TL;DR: Compartmentation of the metabolism of amino acids in brain has been studied in slices of cerebral cortex incubated with sodium, sodium [1‐14C]acetate, sodium‐bicarbonate, or l‐[1‐ 14C]glutamate and in samples of brain after injection in vivo of [3H] acetate.