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IN RECENT studies of glutamic acid metabolism in uivo, the fate of tracer amounts of rqlabelled glutamic acid administered intravenously to rats and mice was investigated in experiments of short duration (LAJTHA, BERL and WAELSCH, 1959). The major portion of the amino acid apparently entered brain, liver, kidney and muscle as the acid and conversion to the amide was not an essential prerequisite for exchange across the blood-brain barrier. The metabolic changes which then ensued were quite rapid, for within 2 min after injection of [14C]glutamic acid, the glutamic acid, gluta-EXPERIMENTAL Material. Uniformly labelled ["Clglutamic acid (1 1 pclpmole) and uniformly labelled [W]aspartic acid (5 pc/pmole) were obtained from Nuclear Chicago Corp. Uniformly labelled [*'C]glutamine (0.93 pc/pmole) was obtained from Merck and Co. of Canada. The purity of the labelled compounds was tested by column and paper chromatography. Animal and organ preparations Intracisterml injection of rat. Sprague-Dawley rats approximately 100 g in weight were used. Under light ether anaesthesia 0.02 ml of a neutralized amino acid solution was injected in the midline The abhreviations used are: GSH, glutathione; GABA, y-aminobutyric acid; TCA, trichloroacetic acid

1. 14C from [1−14C]glucose injected intraperitoneally into mice is incorporated into glutamate, aspartate and glutamine in the brain to a much greater extent than 14C from [2−14C]glucose. This difference for [1−14C]glucose and [2−14C]glucose increases with time. The amount of 14C in C-1 of glutamate increases steadily with time with both precursors. It is suggested that a large part of the glutamate and aspartate pools in brain are in close contact with intermediates of a fast-turning tricarboxylic acid cycle. 2. 14C from [1−14C]acetate and [2−14C]acetate is incorporated to a much larger extent into glutamine than into glutamate. An examination of the time-course of 14C incorporated into glutamine and glutamate reveals that glutamine is not formed from the glutamate pool, labelled extensively by glucose, but from a small glutamate pool. This small glutamate pool is not derived from an intermediate of a fast-turning tricarboxylic acid cycle. 3. It is proposed that two different tricarboxylic acid cycles exist in brain.

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