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

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalBrain Research
Volume1335
DOIs
Publication statusPublished - 04-06-2010
Externally publishedYes

Fingerprint

Acetyl Coenzyme A
Methamphetamine
aspartate N-acetyltransferase
Enzymes
Proteins
Lipid Metabolism
Energy Metabolism
Brain
Magnetic Resonance Spectroscopy
N-acetylaspartate
Only Child
Gene Deletion
Brain Diseases
Acetylation
Myelin Sheath
Aspartic Acid
Brain Injuries
Nervous System
Genes
Organism Cloning

All Science Journal Classification (ASJC) codes

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

Cite this

Ariyannur, Prasanth S. ; Moffett, John R. ; Manickam, Pachiappan ; Pattabiraman, Nagarajan ; Arun, Peethambaran ; Nitta, Atsumi ; Nabeshima, Toshitaka ; Madhavarao, Chikkathur N. ; Namboodiri, Aryan M.A. / Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme : Implications for specialized acetyl coenzyme A metabolism in the CNS. In: Brain Research. 2010 ; Vol. 1335. pp. 1-13.
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Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme : Implications for specialized acetyl coenzyme A metabolism in the CNS. / Ariyannur, Prasanth S.; Moffett, John R.; Manickam, Pachiappan; Pattabiraman, Nagarajan; Arun, Peethambaran; Nitta, Atsumi; Nabeshima, Toshitaka; Madhavarao, Chikkathur N.; Namboodiri, Aryan M.A.

In: Brain Research, Vol. 1335, 04.06.2010, p. 1-13.

Research output: Contribution to journalArticle

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AU - Ariyannur, Prasanth S.

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AU - Manickam, Pachiappan

AU - Pattabiraman, Nagarajan

AU - Arun, Peethambaran

AU - Nitta, Atsumi

AU - Nabeshima, Toshitaka

AU - Madhavarao, Chikkathur N.

AU - Namboodiri, Aryan M.A.

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