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The rate of fixation of carbon dioxide in vivo into aspartate, glutamate, oxoglutarate, and glutamine of cerebral cortex and liver in the absence and presence of elevated concentrations of tissue ammonia was studied. The specific activities of the isolated metabolites were related to the specific activity of the tissue CO2. It was attempted to obtain an approximate steady state level of tissue 14CO2 by maintaining a constant isotope concentration in the venous and arterial blood through continuous intravenous administration of NaH14CO3. 1. In the absence of ammonia, aspartic acid achieved the highest specific activity in both brain and liver; the specific activity of glutamine was greater than that of the glutamic acid in the brain but the reverse was true in the liver. 2. In brain, in the absence of ammonia, the aspartic acid specific activity reached a level 10-25 per cent of that of the tissue CO2 in experiments of 18 min duration, while in liver the specific activity of aspartic acid approached a value twice that of the tissue CO2. 3. In the presence of an increased level of ammonia in brain, the specific activity of glutan1ine increased without a corresponding decrease in specific activities of glutamic or aspartic acids. The amide achieved values 1·3 to 2·3 times that of the aspartic acid and 4-5 times that of the glutamic acid. The average concentration of glutamine in the brain cortex of the cat in the control experiments was 5·8 ± 1·0 (S.D.)μmoles/g (N = 7) which may be compared with the value obtained in previous experiments, 5·3 + 0·6 μmoles/g (N - 61) (BERL et al., 1959, 1961b). For glutamic acid the respective values are 9·6 ± 1·0 μmoles/g (N = 10) and 9·6 ± 1·4 μmoles/g (N = 62). In the experiments in which ammonia was administered (this paper) the average glutamine concentration was found to be 7·7 ± 0·4 μmoles/g (N = 3). In previous experiments in which ammonia was administered for various periods the average concentration was 8·3 ± 0·8 μmoles/g (N - 8), (BERL et al., 1962a). The average aspartic acid concentration in the present experiments was 2·3 ± 0·4 μmoles /g (N = 10). In previous experiments an average concentration of 2·5 ± 0·4 μmoles/g (N = 23) of aspartic acid was found. 4. In liver the α-oxoglutarate had a lower specific activity than glutamate in four of five experiments. In brain, in the experiments of 16-18 min duration the specific activity of the α-oxoglutarate was up to twice that of the glutamate but lower than that of the glutamine. 5. The total amount of CO2 incorporated into the metabolites of the non-protein filtrate from brain tissue was increased in the presence of elevated levels of ammonia. 6. In the presence of elevated levels of ammonia the total amounts of CO2 incorporated into the glutamic and aspartic acids of brain cortex appeared to remain constant but increased four-fold for glutamine. It is concluded that, in brain, CO2 fixation is of considerable significance and can respond with an increased rate to metabolic stress, such as is presented by elevated tissue ammonia. In addition, the data support the conclusion that in brain tissue the glutamic acid-glutamine system is compartmentalized; they also suggest the compartmentalization of α-oxoglutarate metabolism in both brain and liver

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Journal of neurochemistry 11:717-728.

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