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Title: Metabolic fate of /sup 13/N-labeled ammonia in rat brain

Journal Article · · J. Biol. Chem.; (United States)
OSTI ID:5006936

After infusion of physiological concentrations of (/sup 13/N)ammonia for 10 min via one internal carotid artery, the relative specific activities of glutamate, glutamine (..cap alpha..-amino), and glutamine (amide) in rat brain were approximately 1:5:400, respectively. Analysis of metabolites, after infusion of (/sup 13/N)ammonia into one lateral cerebral ventricle, indicated that ammonia entering the brain from the cerebrospinal fluid is also metabolized in a small glutamate pool. Pretreatment with methionine sulfoximine led to a decrease in the label present in brain glutamine following carotid artery infusion of (/sup 13/N)ammonia. /sup 13/N activity in brain glutamate was greater than in the ..cap alpha..-amino group of glutamine. The amount of label recovered in the right cerebral hemisphere, 5 s after a rapid bolus injection of (/sup 13/N)ammonia via the right common carotid artery, was independent of concentration within the bolus over a 1000-fold range indicating that ammonia enters the brain largely by diffusion. In normal rats approximately 60% of the label recovered in brain was incorporated into glutamine, indicating that the t/sub 1//sub///sub 2/ for conversion of ammonia to glutamine in the small pool is in the range of 1 to 3 s or less. The data emphasize the importance of the small pool glutamine synthetase as a metabolic trap for the detoxification of blood-borne and endogenously produced brain ammonia. The possibility that the astrocytes represent the anatomical site of the small pool is considered.

DOE Contract Number:
EE-77-5-02-4268
OSTI ID:
5006936
Journal Information:
J. Biol. Chem.; (United States), Vol. 254:12
Country of Publication:
United States
Language:
English

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