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Metabolism of N-acetyl-l-aspartate in rat brain
Authors:Sheldon L. Miller  Yevgeny Daikhin  Marc Yudkoff
Affiliation:(1) Division of Neurology Research, Children’s Hospital of Philadelphia, Philadelphia, PA;(2) Division of Child Development, Children’s Hospital of Philadelphia, Philadelphia, PA;(3) Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA;(4) Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA;(5) Division of Neurology Research, Abramson Center, Children’s Hospital of Philadelphia, 3517 Civic Center Blvd., 19104 Philadelphia, PA
Abstract:
The abundance and developmental regulation of N-acetylaspartate (NAA) in brain suggest that it plays an important role in brain metabolism. Previous studies demonstrated that NAA transports acetate from the mitochondrion to the cytoplasm where it is utilized for lipid synthesis, however, the metabolic fate of NAA-derived aspartate is not established. To investigate NAA metabolism, rats were injected intracranially with N-([2H3]acetyl)-l-[15N]aspartate ([2H3,15N]NAA) and whole brain metabolites were analyzed using gas chromatography and mass spectrometry techniques (GC/MS). The rapid decline of [2H3,15H]NAA was associated with a rapid appearance of [15N]glutamate, indicating rapid transamination of the [15N]aspartate that was derived from the enzymatic hydrolysis of [2H3,15N]NAA. Inability to detect [15N]NAA in brain extracts in several experiments indicates that the15N moiety is not reutilized for NAA synthesis and suggests one metabolic role of NAA may be the transport of amino nitrogen from the mitochondrion to the cytoplasm.
Keywords:N-acetylaspartate  brain metabolism  aspartate  oxalacetate  amino nitrogen metabolism
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