Metabolic fate of /sup 13/N-labeled ammonia in rat brain
- Cornell Univ., New York, NY
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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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMMONIA
METABOLISM
NITROGEN 13
TRACER TECHNIQUES
BIOCHEMICAL REACTION KINETICS
BRAIN
DIFFUSION
ENZYME ACTIVITY
GLUTAMINE
LABELLED COMPOUNDS
LIGASES
METABOLITES
RATS
UPTAKE
AMIDES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
HYDRIDES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NITROGEN COMPOUNDS
NITROGEN HYDRIDES
NITROGEN ISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RADIOISOTOPES
REACTION KINETICS
RODENTS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques
560305 - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550201 - Biochemistry- Tracer Techniques