Introduction

Tallan1 reported the occurrence of high concentrations (10-14 mM) of N-acetylaspartate (NAA) in cat brain almost 50 years ago. After a long gap, the past 20 years have seen tremendous progress with discoveries such as the NAA metabolic defect in Canavan disease2'3 and the recognition of the value of NAA as an index of neuronal health using magnetic resonance spectroscopy.4-7 However, the biochemical mechanisms of NAA synthesis remain unclear. The early reports on the NAA synthetic enzyme date back nearly 5 decades8-10 and its subcellular localization to mitochondria was indicated in 1979.11 The synthetic enzyme, L-Aspartate N-acetyltransferase (Asp-NAT; EC 2.3.1.17) was characterized only recently as a possible multi-subunit enzyme complex from rat brain.12 However, further molecular characterization of this enzyme remains to be accomplished.

While a number of reports indicate that NAA is localized primarily in neurons in the central nervous system (CNS),5,13-15 the NAA hydrolyzing enzyme aspartoacylase (amidohydrolase 2, ASPA; EC 3.5.1.15) has been localized primarily in oligodendrocytes, the myelinating cells in the CNS.16-19 Unlike Asp-NAT, there has been a body of literature available on the NAA hydrolyzing enzyme, ASPA, after it was first reported in hog kidney.20 ASPA was later detected in brain tissue21 and it was subsequently purified from bovine brain.22 This work led to the identification of the genetic sequence coding ASPA23 and cloning and expression of human and mouse recombinant genes.24,25 Mutations in the gene coding ASPA have been linked to the fatal genetic disorder, Canavan disease.3,26,27

Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD-20814; email, [email protected].

L-Glu

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