Document Detail


Proline, glutamate and glutamine metabolism in mouse brain synaptosomes.
MedLine Citation:
PMID:  6151865     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In nerve terminals, glutamate (Glu) may serve as precursor of the inhibitory neurotransmitter, GABA, and the putative excitatory transmitter, aspartate (Asp), in addition to exerting its own excitatory neurotransmitter role in brain. Glu carbon can originate from glucose through glycolysis and the Krebs cycle, from glutamine (Gln) subsequent to uptake, and from proline (Pro) and ornithine (Orn). Orn, but not Glu, is an effective precursor in nerve terminals of Pro, a putative inhibitory neurotransmitter. [3H]Arg can be converted in mouse brain nerve terminals to Orn, which in turn gives rise to Glu, Pro and GABA. In the present study, the conversion subsequent to uptake of labeled Glu, Gln and Pro to other amino acids was studied in unfractionated and subfractionated synaptosomal particles which layered, respectively, on 1.0 M, 1.2 M, 1.3 M and 1.5 M sucrose after centrifugation in a discontinuous gradient (fractions 1-4, respectively). Fraction 1 contained small synaptosomal fragments with vesicles and almost no mitochondria. Fractions 2 and 3 showed numerous normal-appearing mitochondria-containing synaptosomes, and fraction 4 contained large synaptosomes and more free mitochondria than the other fractions. Glu was readily taken up in all fractions and converted to Asp, Gln and GABA, the greatest formation of Asp from Glu occurring in fractions 2 and 3 and of Gln in fraction 4. In contrast, Gln was taken up poorly in fraction 1 and not metabolized, converted extensively to Glu and GABA in fractions 2-4, giving rise only to very small amounts of Asp in fractions 2 and 3. Although Pro was taken up to the greatest extent in fraction 2, it was by far most readily converted to Glu, Gln and GABA in fraction 1, showing only small amounts of Asp formation in fractions 1-3 and none in 4. There was no significant production of Pro from Glu or Gln or of Arg and Orn from any of the 3 precursors studied. The above results suggest that Glu, Gln and Pro may be taken up largely in different classes of synaptosomes which are distributed among the centrifugally separated fractions and which possess differing transport and metabolic characteristics. Determination of glutamate decarboxylase activity (GAD) indicated that GABA-forming nerve terminals were present in all synaptosomal fractions studied. Amino acid determinations by HPLC in the subfractionated synaptosomes showed a similar distribution for Glu, Asp and GABA contents, peaking in fraction 2, and an inverse relationship of the latter 3 with Arg contents.(ABSTRACT TRUNCATED AT 400 WORDS)
Authors:
J L Johnson; E Roberts
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  323     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  1984 Dec 
Date Detail:
Created Date:  1985-04-15     Completed Date:  1985-04-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  247-56     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / analysis
Animals
Brain / metabolism*
Brain Chemistry
Cell Fractionation / methods
Glutamate Decarboxylase / metabolism
Glutamates / metabolism*
Glutamic Acid
Glutamine / metabolism*
Mice
Proline / metabolism*
Synaptosomes / analysis,  metabolism
Grant Support
ID/Acronym/Agency:
NS18858/NS/NINDS NIH HHS; NS18859/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Glutamates; 147-85-3/Proline; 56-85-9/Glutamine; 56-86-0/Glutamic Acid; EC 4.1.1.15/Glutamate Decarboxylase

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


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