N-Acetylaspartic acid explained

N-Acetylaspartic acid, or N-acetylaspartate (NAA), is a derivative of aspartic acid with a formula of C₆H₉NO₅ and a molecular weight of 175.139.

NAA is the second-most-concentrated molecule in the brain after the amino acid glutamate. It is detected in the adult brain in neurons,^[1] oligodendrocytes and myelin^[2] and is synthesized in the mitochondria from the amino acid aspartic acid and acetyl-coenzyme A.^[3]

Function

The various functions served by NAA are under investigation, but the primary proposed functions include:

• Neuronal osmolyte that is involved in fluid balance in the brain
• Source of acetate for lipid and myelin synthesis in oligodendrocytes, the glial cells that myelinate neuronal axons
• Precursor for the synthesis of the neuronal dipeptide N-Acetylaspartylglutamate
• Contributor to energy production from the amino acid glutamate in neuronal mitochondria

In the brain, NAA was thought to be present predominantly in neuronal cell bodies, where it acts as a neuronal marker,^[4] but it is also free to diffuse throughout neuronal fibers.^[5]

Applications

However, the recent discovery of a higher concentration of NAA in myelin and oligodendrocytes than in neurons raises questions about the validity of the use of NAA as a neuronal marker. NAA gives off the largest signal in magnetic resonance spectroscopy of the human brain. The levels measured there are decreased in numerous neuropathological conditions ranging from brain injury to stroke to Alzheimer's disease. This fact makes NAA a potential diagnostic molecule for doctors treating patients with brain damage or disease.

NAA may be a marker of creativity.^[6] High NAA levels in the hippocampus are related to better working memory performance in humans.^[7] Whole-brain levels of NAA have also been found to be positively correlated with educational attainment in adults.^[8]

NAA may function as a neurotransmitter in the brain by acting on metabotropic glutamate receptors.^[9]

See also

• Aspartoacylase
• Canavan disease

Further reading

• Book: John . Moffett. Suzannah B.. Tieman. Daniel R. . Weinberger. Joseph T. . Coyle . Aryan M. A. . Namboodiri . vanc . [{{google books |plainurl=y |id=tR44q6WWRBgC}} N-Acetylaspartate: A Unique Neuronal Molecule in the Central Nervous System]. 21 October 2006. Springer Science & Business Media. 978-0-387-30172-3.
• Jung RE, Gasparovic C, Chavez RS, Flores RA, Smith SM, Caprihan A, Yeo RA . Biochemical support for the "threshold" theory of creativity: a magnetic resonance spectroscopy study . The Journal of Neuroscience . 29 . 16 . 5319–25 . April 2009 . 19386928 . 2755552 . 10.1523/JNEUROSCI.0588-09.2009 .

External links

• GeneReviews/NCBI/UW/NIH entry on Canavan disease

Notes and References

1. Simmons ML, Frondoza CG, Coyle JT . Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies . Neuroscience . 45 . 1 . 37–45 . 1991 . 1754068 . 10.1016/0306-4522(91)90101-s . 24071454 .
2. Nordengen K, Heuser C, Rinholm JE, Matalon R, Gundersen V . Localisation of N-acetylaspartate in oligodendrocytes/myelin . Brain Structure & Function . 220 . 2 . 899–917 . March 2015 . 24379086 . 10.1007/s00429-013-0691-7 . 475973 .
3. Patel TB, Clark JB . Synthesis of N-acetyl-L-aspartate by rat brain mitochondria and its involvement in mitochondrial/cytosolic carbon transport . The Biochemical Journal . 184 . 3 . 539–46 . December 1979 . 10.1042/bj1840539 . 540047 . 1161835 .
4. Chatham JC, Blackband SJ . Nuclear magnetic resonance spectroscopy and imaging in animal research . ILAR Journal . 42 . 3 . 189–208 . 2001 . 11406719 . 10.1093/ilar.42.3.189 . free .
5. Najac C, Branzoli F, Ronen I, Valette J . Brain intracellular metabolites are freely diffusing along cell fibers in grey and white matter, as measured by diffusion-weighted MR spectroscopy in the human brain at 7 T . Brain Structure & Function . 221 . 3 . 1245–54 . April 2016 . 25520054 . 4878649 . 10.1007/s00429-014-0968-5 .
6. Web site: Creativity chemical favours the smart. Linda. Geddes.
7. Kozlovskiy S, Vartanov A, Pyasik M, Polikanova I . 2012 . Working memory and N-acetylaspartate level in hippocampus, parietal cortex and subventricular zone . International Journal of Psychology . 47 . 584 . 10.1080/00207594.2012.709117 . free .
8. 30 October 2012 . The whole-brain N-acetylaspartate correlates with education in normal adults . Glodzik L, Wu WE, Babb JS, Achtnichts L, Amann M, Sollberger M, Monsch AU, Gass A, Gonenb O . Psychiatry Research: Neuroimaging . 204 . 1 . 49–54 . 10.1016/j.pscychresns.2012.04.013 . 23177924 . 3508436 .
9. Yan HD, Ishihara K, Serikawa T, Sasa M . Activation by N-acetyl-L-aspartate of acutely dissociated hippocampal neurons in rats via metabotropic glutamate receptors . Epilepsia . 44 . 9 . 1153–9 . September 2003 . 12919386 . 10.1046/j.1528-1157.2003.49402.x . 39902618 . free .