Document Detail


The metabolic fate of 13N-labeled ammonia in rat brain.
MedLine Citation:
PMID:  36379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
13N-labeled ammonia was used to study the cerebral uptake and metabolism of ammonia in conscious rats. After infusion of physiological concentrations of [13N]ammonia for 10 min via one internal carotid artery, the relative specific activities of glutamate, glutamine (alpha-amino), and glutamine (amide) in brain were approximately 1:5:400, respectively. The data are consistent with the concept that ammonia, entering the brain from the blood, is metabolized in a small pool of glutamate that is both rapidly turning over and distinct from a larger tissue glutamate pool (Berl, S., Takagaki, G., Clarke, D.D., and Waelsch, H. (1962) J. Biol. Chem. 237, 2562-2569). Analysis of 13N-metabolites, after infusion of [13N]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 of rats with methionine sulfoximine led to a decrease in the label present in brain glutamine (amide) following carotid artery infusion of [13N]ammonia. On the other hand, 13N activity in brain glutamate was greater than that in the alpha-amino group of glutamine, i.e. following methionine sulfoximine treatment the expected precursor-product relationship was observed, indicating that the two pools of glutamate in the brain were no longer metabolically distinct. The amount of label recovered in the right cerebral hemisphere, 5 s after a rapid bolus injection of [13N]ammonia via the right common carotid artery, was found to be independent of ammonia concentration within the bolus over a 1000-fold range. This finding indicates that ammonia enters the brain from the blood largely by diffusion. In normal rats that were killed by a freeze-blowing technique 5 s after injection of an [13N]ammonia bolus, approximately 60% of the label recovered in brain had already been incorporated into glutamine, indicating that the t1/2 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.
Authors:
A J Cooper; J M McDonald; A S Gelbard; R F Gledhill; T E Duffy
Related Documents :
2357649 - Regional cerebral glucose metabolism in turner syndrome.
1323469 - Central benzodiazepine receptors in human brain: estimation of regional bmax and kd val...
2339969 - Brain glucose utilization under high sensory activation: hypoactivation of prefrontal c...
18647619 - A new method for determining blood-brain barrier integrity based on intracardiac perfus...
1313939 - Chronic lithium treatment prevents the dexamethasone-induced increase of brain polyamin...
6609929 - Regional kinetic constants and cerebral metabolic rate for glucose in normal human volu...
8973809 - Subpallidal outputs to the nucleus accumbens and the ventral tegmental area: anatomical...
2230919 - Characteristics of electrically induced locomotion in rat in vitro brain stem-spinal co...
21672789 - Evolution and function in serotonergic systems.
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  254     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1979 Jun 
Date Detail:
Created Date:  1979-08-16     Completed Date:  1979-08-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4982-92     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Ammonia / metabolism*
Animals
Biological Transport
Blood-Brain Barrier
Brain / drug effects,  metabolism*
Glutamate Dehydrogenase / metabolism
Glutamate-Ammonia Ligase / metabolism
Male
Methionine Sulfoximine / pharmacology
Nitrogen Isotopes
Rats
Chemical
Reg. No./Substance:
0/Nitrogen Isotopes; 1982-67-8/Methionine Sulfoximine; 7664-41-7/Ammonia; EC 1.4.1.2/Glutamate Dehydrogenase; EC 6.3.1.2/Glutamate-Ammonia Ligase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Latent proteinase activity of gamma-glutamyl transpeptidase light subunit.
Next Document:  Stereospecificity of sodium borohydride reduction of tyrosine decarboxylase from Streptococcus faeca...