http://n-acetylaspartate.com/PDF%20files/NAA%20Review.pdf

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

N-Acetyl-L-Aspartic acid: A literature review of a compound prominent in 1H-NMR spectroscopic studies of brain

N-acetylaspartate in neuropsychiatric disorders.

Initially described by Tallan et al. [1], N-acetyl aspartate (NAA) is found at very high concentrations in the mammalian brain (6–7 Ìmol/g in human brain) and is second only to glutamate in terms of free amino acid concentrations. Very limited concentrations are found in other tissues, e.g. liver, kidney, muscle. Regional studies on mouse have indicated its presence in all areas of the brain, with particularly high concentrations in cerebral grey matter (7.1 Ìmol/g) and low concentrations in the medulla (3.1 Ìmol/g) [2]. With a molecular mass of 175 Da, NAA has a double negative charge at physiological pH, necessitating active transport across biological membranes (fig. 1). Early studies by Buniatian et al. [3] demonstrated that NAA may act as an acetyl group donor to glucosamine and choline. Furthermore, D’Adamo and Yatsu [4] using double radioactively labelled NAA showed that the acetyl group is incorporated into brain lipids 3 times more effectively than acetate alone. Additionally, in the immature rat brain NAA rapidly increases as the brain develops [2], and the maximum incorporation of the acetyl moiety of NAA into brain lipids occurs during the period of myelination [5]. The results of all these studies are consistent with a role for NAA in myelination. Fig. 1. Structure of N-acetyl aspartate (NAA).

N-Acetyl Aspartate: A Marker for Neuronal Loss or Mitochondrial Dysfunction

1. The synthesis and efflux of N-acetyl-l-aspartate from brain mitochondria of rats of different ages has been studied. 2. Brain mitochondrial State 3 (+ADP) respiration rate, using 10mm-glutamate and 2.5mm-malate as substrates, increases during the suckling period and reaches approx. 50% of the adult value at 17 days after birth [adult State 3 respiration rate=160+/-7ng-atoms of O/min per mg of mitochondrial protein(mean+/-s.d.; n=3)]. 3. The influence of 5mm-pyruvate or 10mm-dl-3-hydroxybutyrate on aspartate efflux from brain mitochondira from rats of different ages oxidizing glutamate and malate was studied. In all cases the aspartate efflux in State 3 was greater than in State 4, but, whereas the aspartate efflux in State 3 increased as the animals developed, that of State 4 showed only a small increase. However, the rate of aspartate efflux in the presence of pyruvate or 3-hydroxybutyrate as well as glutamate and malate was approx. 60-65% of that in the presence of glutamate and malate alone. 4. An inverse relationship between aspartate efflux and N-acetylaspartate efflux was observed with adult rat brain mitochondria oxidizing 10mm-glutamate and 2.5mm-malate in the presence of various pyruvate concentrations (0-5mm). 5. N-Acetylaspartate efflux by brain mitochondria of rats of different ages was studied in States 3 and 4, utilizing 5mm-pyruvate or 10mm-dl-3-hydroxybutyrate as acetyl-CoA sources. A similar pattern of increase during development was seen in State 3 for N-acetylaspartate efflux as for aspartate efflux (see point 3 above). Also only very small increases in N-acetylaspartate efflux occurred during development in State 4.6. Rat brain mitochondria in the presence of iso-osmotic N-acetylaspartate showed some swelling which was markedly increased in the presence of malate. 7. It is concluded that N-acetylaspartate may be synthesized and exported from both neonatal and adult rat brain mitochondria. It is proposed that the N-acetylaspartate is transported by the dicarboxylic acid translocase and may be an additional mechanism for mitochondrial/cytosolic carbon transport to that of citrate.

Homer Knizley

Papers

The Enzymatic Synthesis of N-Acetyl-l-aspartic Acid by a Water-insoluble Preparation of a Cat Brain Acetone Powder