No abstract

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.

No abstract

No abstract

No abstract

INTRODUCTIONTHE evidence for a significant role of glutamic acid in the metabolism of nervous tissue rests almost exclusively on results obtained with isolated tissue preparations and o n the fact of the high concentration ofglutamic acid in this tissue (for reviews see WAELSCH , 1952, 1957 STRECKER, 1957). Although changes of glutamic acid concentration in insulin hypoglycemia (DAWSON, 1950; HIMWICH and SULLIVAN, 1956) and the results of perfusion experiments (BOWLANGER et al., 1950) are highly suggestive of a rapid glutamic acid metabolism, the rate of the conversion of the dicarboxylic acid has not been studied. Only very recently data on the rate of decarboxylation of glutamic acid t o y-aminobutyric acid* in rico have become available (ROBERTS et al., 1958). In order t o contribute t o the understanding of the in vico metabolism of glutamic acid in the brain, the penetration of 14C-labelled glutamic acid into this organ a s well as its conversion to glutamine, Gaba, and GSH in brain, liver, kidney and muscle was studied.Previous work in this laboratory showed no significant increase of the concentration of glutamic acid in the brains of animals in short time experiments when the concentration of the amino acid in the blood of rats or mice was raised from thirty to fifty times. The glutamic acid concentration of liver and muscle was moderately increased while a large increase was found in the kidneys. On the other hand, when glutamine was administered, the amide concentration increased in all organs, a n increase which was accompanied by an elevation of glutamic acid concentration in liver, kidney and blood. It appears, therefore, that glutamine penetrates into the organs, and especially into brain, at a higher rate than glutamic acid, and that glutamine is deamidated rapidly to glutamic acid (SCHWERIN, BESSMAN and WAELSCH, 1950). The possibility cannot be dismissed that the failure to observe a net increase of glutamic acid in brain after the administration of the amino acid is the result of rapid metabolism and removal of any additional amounts, although it should be remembered that both in liver and in kidney increases in glutamic acid could be demonstrated after the administration of either the acid or its amide.Recently, in further studies of the amino acid and protein metabolism of the brain, it was found that after systemic administration of minute amounts of the 14CThe following abbreviations are used in this paper: glutathione, GSH; 1P-aminobutyric acid, Gaba; tnchloroacetic acid, TCA.

No abstract