Edward M. Lieberman, Mohit Achreja and Albert K. Urazaev*
The biosynthesis of n-acetylaspartylglutamate (NAAG) along with its precursor, N-acetylaspartate (NAA), has been of interest since they were first shown to be present in nerve tissue in relatively high concentration approximately 4 decades ago1,2. In 1973 Reichelt and Kvamme3 demonstrated that biosynthesis of NAAG occurred in homogenates of mouse brain with an absolute dependence on ATP and NAA as a primary substrate. In addition, inhibitors of cytoplasmic and mitochondrial protein synthesis were without effect suggesting that an enzyme-mediated rather than post-translational protein processing was responsible for NAAG biosynthesis. This work has since been confirmed in spinal sensory ganglion4 and more recently in rat spinal cord 5.
NAAG, considered to have appeared late in evolution6, has now been shown to be present in axons and glia of crayfish medial giant nerve fibers along with its glial membrane-associated degradative enzyme, Glutamate Carboxypeptidase II (GCPII) and the glial group II metabotropic glutamate receptor, for which it is a specific agonist7-
II. The metabotropic glutamate receptor is responsible for regulating glial membrane potential, nitric oxide production12 and regulation of GCPII. There is also developing evidence that the mGLURII may participate in nervous system volume regulation and perineural K+ homeostasis 13 -1 5 .
In this report we review recently published and ongoing investigations from our laboratory that show that there is a significant presence of NAAG and NAA in both axoplasm and glia of the medial giant nerve fiber of the crayfish and that their synthesis occurs in the presence of a single substrate - glutamate. Intermediates of NAAG synthesis, e.g. aspartate and NAA, are also effective substrates and glutamine can be rapidly deaminated by glutaminase present in axons and glia of the crayfish nerve fiber16
E.M. Lieberman and M. Achreja, Dept. of Physiology, The Brody School of Medicine of East Carolina University, Greenville, NC 27834; A.K. Urazaev, Present address: Dept. of Biological Sciences, Purdue University, West Lafayette, IN 47907
forming glutamate, allowing it to enter into the NAAG biosynthetic pathway.
Was this article helpful?