Document Detail


Role of specific aminotransferases in de novo glutamate synthesis and redox shuttling in the retina.
MedLine Citation:
PMID:  11746419     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study aminotransferase inhibitors were used to determine the relative importance of different aminotransferases in providing nitrogen for de novo glutamate synthesis in the retina. Aminooxyacetate, which inhibits all aminotransferases, blocked de novo glutamate synthesis from H(14)CO(3)(-) by more than 60%. Inhibition of neuronal cytosolic branched chain amino acid transamination by gabapentin or branched chain amino acid transport by the L-system substrate analog, 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylic acid, lowered total de novo synthesis of glutamate by 30%, suggesting that branched chain amino acids may account for half of the glutamate nitrogen contributed by transamination reactions. L-cycloserine, an inhibitor of alanine aminotransferase, inhibited glutamate synthesis less than 15% when added in the presence of 5 mM pyruvate but 47% in the presence of 0.2 mM pyruvate. Although high levels of pyruvate blunted the inhibitory effectiveness of L-cycloserine, the results indicate that, under physiological conditions, alanine as well as branched chain amino acids are probably the predominant sources of glutamate nitrogen in ex vivo retinas. The L-cycloserine results were also used to evaluate activity of the malate/aspartate shuttle. In this shuttle, cytosolic aspartate (synthesized in mitochondria) generates cytosolic oxaloacetate that oxidizes cytosolic NADH via malate dehydrogenase. Because L-cycloserine inhibits cytosolic but not mitochondrial aspartate aminotransferase, L-cycloserine should prevent the utilization of aspartate but not its generation, thereby increasing levels of (14)C-aspartate. Instead, L-cycloserine caused a significant decline in (14)C-aspartate. The results suggest the possibility that shuttle activity is low in retinal Müller cells. Low malate/aspartate shuttle activity may be the molecular basis for the high rate of aerobic glycolysis in retinal Müller cells.
Authors:
K F LaNoue; D A Berkich; M Conway; A J Barber; L Y Hu; C Taylor; S Hutson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  66     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2001-12-17     Completed Date:  2002-02-01     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  914-22     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc.
Affiliation:
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetates / pharmacology
Alanine Transaminase / metabolism
Amines*
Amino Acids, Branched-Chain / antagonists & inhibitors,  metabolism
Animals
Antimetabolites / pharmacology
Aspartate Aminotransferases / metabolism
Cyclohexanecarboxylic Acids*
Cycloserine / pharmacology
Cytosol / enzymology*
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
Glutamic Acid / biosynthesis*
Mitochondria / enzymology*
Neuroglia / enzymology*
Oxidation-Reduction
Rats
Rats, Sprague-Dawley
Retina / enzymology*
Subcellular Fractions
Transaminases / metabolism*
gamma-Aminobutyric Acid*
Grant Support
ID/Acronym/Agency:
NS 38641/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Acetates; 0/Amines; 0/Amino Acids, Branched-Chain; 0/Antimetabolites; 0/Cyclohexanecarboxylic Acids; 0/Enzyme Inhibitors; 0/Excitatory Amino Acid Antagonists; 56-12-2/gamma-Aminobutyric Acid; 56-86-0/Glutamic Acid; 68-41-7/Cycloserine; 6CW7F3G59X/gabapentin; EC 2.6.1.-/Transaminases; EC 2.6.1.1/Aspartate Aminotransferases; EC 2.6.1.2/Alanine Transaminase

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


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