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Notes: A vertically dispersing high-energy spherical grating monochromator (HESGM) has been installed on the synchrotron radiation source (SRS) at the Daresbury Laboratory. The instrument has no entrance slit and provides a high intensity source of x rays of energy 250–1400 eV focused into a small spot suitable for surface spectroscopy. Photoabsorption features of 240 meV have been resolved, but the resolution of the instrument is dependent on the SRS stored beam current. The degree of linear polarization has been measured at the carbon K edge to be 0.80.

Notes: Abstract— The distibution of 14C in the brains of rats that had been given [U-14C]glucose (10μCi/100g body wt.) at 10 min before death was followed for 20 min post mortem. The results indicated that the input of glucose-carbon into the tricarboxylic acid cycle stopped instantaneously after death. Although the proportion (more than 40 per cent) of tissue-14C combined in the amino acids associated with the cycle did not change significantly, there was a characteristic redistribution of 14C within the amino acid fraction after death: significantly, the 14C content of glutamate decreased andthat of GABA increased. The GABA/glutamate specific radioactivity ratio which in vivo was 0-58, increased progressively in the first 5 min after death, reaching a value of 0-93. However, by 5 min the rise in the ratio stopped abruptly, although GABA accumulation continued at about half the initial rate beyond that time. These results indicated that GA BA formation is compartmented in the brain andpermitted the evaluation of certain kinetic parameters of the two compartments which could be distinguished under the experimental conditions. One of the compartments was evidently a summation of a number of subcompartments which had certain features in common, such as a low GABA flux relative to the amount of glutamate. The properties of the other compartment were compatible with those of nerve terminals functioning with GABA as the transmitter. This compartment contained about 2 per cent of the total glutamate, but the glutamate pool was labelled about three times more than the average. Further, this compartment accounted for about 50 per cent of the total GABA formation flux andcontained GABA in high concentrations (the probable values were about seven times the mean).

Notes: 〈list xml:id="l1" style="custom"〉1The rapid and extensive conversion of glucose-carbon into amino acids is an index of the final coordination of the mechanisms underlying energy metabolism in the adult brain. This phenomenon develops in the rat during a short period extending from 10 to about 19 days after birth. The underlying factors have been analysed.〈list xml:id="l2" style="custom"〉2The development of the pattern of distribution of glucose-carbon characteristic of the adult brain was markedly influenced by the thyroid state of the animals. The age-curve for the conversion of glucose-carbon into brain amino acids was displaced to the left after treatment with thyroid hormone (T3) in infancy thus indicating an accelerated maturation. Conversely, neonatal thyroidectomy resulted in a significant retardation in the conversion of glucose-carbon into amino acids.〈list xml:id="l3" style="custom"〉3The specific radioactivity of glutamate increased five-fold in the brain of normal rats from the 10th to the 19th day of age. The values (as a percentage of those for littermate controls) were 220 in the case of the 10 day-old thyroid treated rats and about 30 for the 19 day-old thyroid deficient animals. At the age of 10 days neither treatment affected the concentration of glutamate which was also only slightly less than the control values in the brain of 19 day-old thyroid deficient animals (–17 per cent).〈list xml:id="l4" style="custom"〉4Specific pool(s) of glutamate associated with the formation of GABA can be demonstrated in the brain of 19 day-old rats after administration of [U-14C]glucose as a result of anoxia post mortem. These pools did not develop in the brain of 10 day-old animals. Neonatal thyroidectomy retarded the development of these glutamate pools.〈list xml:id="l5" style="custom"〉5Evidence is summarized which indicates that the development of the rapid conversion of glucose-carbon into amino acids reflects the enlargement, during maturation, of the metabolic compartments which are associated with neuronal processes.

Notes: —The effect of 1-hydroxy-3-aminopyrrolidone-2(HA-966), a CNS depressant, was studied on the metabolism of [14C]glucose and [3H]acetate in the brain in mice. HA-966 had a marked effect on glucose metabolism. The conversion of glucose carbon into amino acids associated with the tricarboxylic acid cycle (‘cycle’) was severely reduced, while the concentration of brain glucose was approximately doubled. Relative to the specific radioactivity of glucose in the brain, the specific radioactivity of alanine was 60–70 per cent of the control, indicating a reduction in the rate of glycolysis, and those of the‘cycle’amino acids were also lowered. A reduction in‘cycle’flux of 30–35 per cent was estimated. It was established that the depressed glucose utilization flux was not due to either impaired uptake of glucose from blood to brain or to hypothermia. In contrast to [14C]glucose, there was no change in the labelling of the amino acid fraction from [3H]acetate, which is preferentially metabolized in the 'small’compartment believed to be associated with glia. Thus it seems that CNS depression caused by HA-966 resulted in a selective decrease in energy production in the‘large’metabolic compartment where glucose is oxidized preferentially and which is believed to be associated with neuronal structures.The results also suggested that communication between the metabolic compartments mediated via glutamine and GABA was reduced, since the labelling from [3H]acetate of glutamine was increased and that of GABA decreased by HA-966.

Notes: Abstract— Thiamine deficiency produced by administration of pyrithiamine to rats maintained on a thiamine-deficient diet resulted in a marked disturbance in amino acid and glucose levels of the brain.In the two pyrithiamine-treated groups of rats (Expt. A and Expt. B) there was a significant decrease in the levels of glutamate (23%, 9%) and aspartate (42%, 57%), and an increase in the levels of glycine (26%, 27%) in the brain, irrespective of whether the animals showed signs of paralysis (Expt. A) or not (Expt. B). as a result of thiamine deficiency. A significant decrease in the levels of γ-aminobutyrate (22%) and serine (28%) in the brain was also observed in those pyrithiamine-treated rats which showed signs of paralysis (Expt. A). Threonine content increased by 57% in Expt. A and 40% in Expt. B in the brain of pyrithiamine-treated rats, but these changes were not statistically significant.The utilization of [U-14C]glucose into amino acids decreased and accumulation of glucose and [U-14C]glucose increased significantly in the brain after injection of [U-14C]glucose to pyrithiamine-treated rats which showed abnormal neurological symptoms (Expt. A). The decrease in 14C-content of amino acids was due to decreased conversion of [U-14C]glucose into alanine, glutamate, glutamine, aspartate and γ-aminobutyrate. The flux of [14C]glutamate into glutamine and γ-aminobutyrate also decreased significantly only in the brain of animals paralysed on treatment with pyrithiamine.The decrease in the labelling of, amino acids was attributed to a decrease in the activities of pyruvate dehydrogenase and α-oxoglutarate dehydrogenase in the brain of pyrithiamine-treated rats. The measurement of specific radioactivity of glucose, glucose-6-phosphate and lactate also indicated a decrease in the activities of glycolytic enzymes in the brain of pyrithiamine-treated animals in Expt. A only. It was suggested that an alteration in the rate of oxidation in vivo of pyruvate in the brain of thiamine-deficient rats is controlled by the glycolytic enzymes, probably at the hexokinase level.The lack of neurotoxic effect and absence of significant decrease in the metabolism of [U-14C]glucose in the brain of pyrithiamine-treated animals in Expt. B were probably due to the fact that animals in Expt. B were older and weighed more than those in Expt. A, both at the start and the termination of the experiments.