Tricarboxylic acid-cycle metabolism in brain. Effect of fluoroacetate and fluorocitrate on the labelling of glutamate aspartate, glutamine and γ-amino butyrate

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.