title: Evidence that aspartate aminotransferase activity and ketodicarboxylate carrier function are essential for biosynthesis of transmitter glutamate.
abstract: Based on the selective inhibition of glutamate release in cerebellar granule cells in primary cultures by the aspartate aminotransferase inhibitor, aminooxyacetic acid, and by the ketodicarboxylate carrier inhibitor, phenylsuccinate, a novel model for synthesis of transmitter glutamate is suggested: Glutamate is formed from glutamine in the mitochondrial intramembrane space by phosphate-activated glutaminase, transported across the inner membrane in exchange with aspartate, transaminated in the matrix to alpha-ketoglutarate, which via the ketodicarboxylate carrier is transferred to the cytoplasm, and transaminated to form transmitter glutamate. Such a mechanism would explain the functional role of aspartate aminotransferase in glutamatergic neurons.
mesh_terms: D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology*; D003035:Cobalt / Q000494:pharmacology; D005971:Glutamates / Q000096:biosynthesis*; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D051379:Mice; D013386:Succinates / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D005971:Glutamates; D013386:Succinates; D005973:Glutamine; D000625:Aminooxyacetic Acid; D001224:Aspartic Acid; D003035:Cobalt; D018698:Glutamic Acid; C017625:2-phenylsuccinate; D001219:Aspartate Aminotransferases; C018021:cobaltous chloride; D002122:Calcium Chloride