N-Acetyl-L-aspartate is synthesized primarily in neurons, continuously released into interstitial space in the brain, and taken up by glial cells for subsequent hydrolysis and use in myelin synthesis.1-3 The intraneuronal concentration of N-acetyl-L-aspartate is ~15 mM while the extracellular concentration is ~100 ^M.4, 5 The synthesis of N-acetyl-L-aspartate in neurons and the hydrolysis of N-acetyl-L-aspartate in glial cells are consistent with the findings that neurons contain high levels of this compound whereas glial cells contain only low levels. N-Acetyl-L-aspartate is also present in retina where a similar situation may exist with respect to the differential functions of neurons and glia in terms of synthesis and degradation of this compound.6 The presence of high concentrations of N-acetyl-L-aspartate in neurons is the basis for the clinical utility of measurements of the levels of this compound in the brain as an indicator of surviving neurons under pathological conditions.3 The physiological function of N-acetyl-L-aspartate in neurons is not known, but the hydrolysis of this compound in glial cells with subsequent metabolic utilization of the released acetate is believed to be essential for optimal myelin synthesis.1-3 The enzyme responsible for the degradation of N-acetyl-L-aspartate in glial cells is aspartoacylase II.7 Genetic deficiency of aspartoacylase II leads to Canavan disease, a disorder associated with mental retardation, spongy degeneration of white matter in the brain, and optic neuropathy.8 Aspartoacylase II is a cytoplasmic enzyme and therefore the extracellular N-acetyl-L-aspartate has to be first transported into glial cells

* Vadivel Ganapathy, Medical College of Georgia, Augusta, Georgia 30912, USA. Takuya Fujita, Department of Biochemical Pharmacology, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.

before the enzyme can have access to this compound. This raises the issue of the cellular processes that mediate the entry of this compound into glial cells. N-Acetyl-L-aspartate exists as a dicarboxylate anion at physiological pH and therefore non-specific diffusion is not likely to be a significant contributor to this process. Therefore, glial cells must possess a transport mechanism for the uptake of this compound. Here we review the evidence for the presence of an active transport system for N-acetyl-L-aspartate in glial cells and for molecular identity of this transport system with the high-affinity sodium/carboxylate cotransporter NaC3 (formerly known as NaDC3).

Natural Treatments For Dandruff

Natural Treatments For Dandruff

Stop Your Scalp From Snowing! Finally... A Real Cure for Dandruff! No medication! No weird cures! No messy creams, smelly solutions or strange diets! Are you sick to death of being sold products that could make the problem worse? Are you sick of the shampoos and conditioners that make your head smell like sulphur? If so then try a permanent revolutionary treatment for dandruff!

Get My Free Ebook

Post a comment