Evidence that aspartate aminotransferase activity and ketodicarboxylate carrier function are essential for biosynthesis of transmitter glutamate.
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.
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
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