Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: Implications for specialized acetyl coenzyme A metabolism in the CNS

Prasanth S. Ariyannur, John R. Moffett, Pachiappan Manickam, Nagarajan Pattabiraman, Peethambaran Arun, Atsumi Nitta, Toshitaka Nabeshima, Chikkathur N. Madhavarao, Aryan M.A. Namboodiri

研究成果: Article

60 引用 (Scopus)

抜粋

N-acetylaspartate (NAA) is a concentrated, neuron-specific brain metabolite routinely used as a magnetic resonance spectroscopy marker for brain injury and disease. Despite decades of research, the functional roles of NAA remain unclear. Biochemical investigations over several decades have associated NAA with myelin lipid synthesis and energy metabolism. However, studies have been hampered by an inability to identify the gene for the NAA biosynthetic enzyme aspartate N-acetyltransferase (Asp-NAT). A very recent report has identified Nat8l as the gene encoding Asp-NAT and confirmed that the only child diagnosed with a lack of NAA on brain magnetic resonance spectrograms has a 19-bp deletion in this gene. Based on in vitro Nat8l expression studies the researchers concluded that many previous biochemical investigations have been technically flawed and that NAA may not be associated with brain energy or lipid metabolism. In studies done concurrently in our laboratory we have demonstrated via cloning, expression, specificity for acetylation of aspartate, responsiveness to methamphetamine treatment, molecular modeling and comparative immunolocalization that NAT8L is the NAA biosynthetic enzyme Asp-NAT. We conclude that NAA is a major storage and transport form of acetyl coenzyme A specific to the nervous system, thus linking it to both lipid synthesis and energy metabolism.

元の言語English
ページ(範囲)1-13
ページ数13
ジャーナルBrain Research
1335
DOI
出版物ステータスPublished - 04-06-2010
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

これを引用

Ariyannur, P. S., Moffett, J. R., Manickam, P., Pattabiraman, N., Arun, P., Nitta, A., Nabeshima, T., Madhavarao, C. N., & Namboodiri, A. M. A. (2010). Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: Implications for specialized acetyl coenzyme A metabolism in the CNS. Brain Research, 1335, 1-13. https://doi.org/10.1016/j.brainres.2010.04.008