Amino Acid and Protein Metabolism‐vi Cerebral Compartments of Glutamic Acid Metabolism

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

Simultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR

“…1995 tose phosphate shunt, degradation of proteins, and influx of unlabeled lactate, pyruvate, and ketone bodies from the blood. The rate of protein degrada tion is negligible in rats [0.3% of V tca (calculated from Berl et al, 1961)] and is probably slower in humans. Knudsen et al (1991) reported a value of 0.08 ± 0.03 J.Lmol min -I g-I (n = 18) for the uni directional influx of lactate in humans, which cor responds to a contribution of 10 ± 3% to the carbon flux into the TCA cycle.…”

[1‐13C]Glucose metabolism in rat cerebellar granule cells and astrocytes in primary culture

“…Last, in the case of granule cells, glutamate C2 and C3 enrichments were equivalent; the carbon flux through the pyruvate carboxylase route was evaluated to be around 15% of the carbon flux through the citrate synthetase route. In astrocytes, glutamate C2 enrichment was higher than that of C3, which could be explained by a pyruvate carboxylase activity much more active in these cells than in granule cells.In the brain, the concept of the existence of two compartmentalized citric acid cycles has emerged from studies on neurotransmitter amino acids (Berl et al, 1961 ;Van den Berg et al, 1969; Hertz, 1979). The cellular basis of the metabolic compartmentation has been more specifically apprehended by analyzing the pools of glutamate and glutamine in brain cells.…”

The Effect of Blood Glutamate Scavengers Oxaloacetate and Pyruvate on Neurological Outcome in a Rat Model of Subarachnoid Hemorrhage

“…Teichberg [65] and Teichberg et al [30] used microdialysis probes in rats to demonstrate that the artificial decrease of blood glutamate with blood glutamate scavengers decreases the concentration of glutamate in rats' ECF [30,65]. Campos et al further showed that lower blood glutamate levels and higher levels of GOT were associated with better neurological outcome in patients after ischemic stroke [41][42][43].…”

“…In addition to astroglial and neuronal membrane glutamate transporters, glutamate transporters are also present on the anti-luminal side of the brain capillary endothelial cells [29,30]. These transporters provide an additional pathway for glutamate elimination from the brain via a brain-to-blood efflux of glutamate [29,[30][31][32][33].…”

“…This in turn facilitates the brain-to-blood glutamate efflux, thereby limiting the neurotoxic effects of glutamate. Treatments with blood glutamate scavengers oxaloacetate, pyruvate, GOT, and glutamatepyruvate transaminase have been shown to effectively improve neurological recovery after traumatic brain injury (TBI) [35][36][37][38] and stroke [39][40][41][42][43], with a concomitant decrease in blood glutamate levels [30,34].…”