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.

doi:10.1016/j.brainres.2010.04.008

Cited by 103 publications

(95 citation statements)

References 52 publications

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“…NAA is synthesized from aspartate and acetyl-coenzyme A in a reaction catalyzed by aspartate N-acetyltransferase (Asp-NAT) (Moffett et al 2007; Ariyannur et al 2010). There is not yet a consensus about the subcellular localization of NAA synthesis or about the physiological functions of NAA.…”

Section: Naamentioning

confidence: 99%

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

Maddock

Buonocore

2011

Current Topics in Behavioral Neurosciences

226

196

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The measurement of brain metabolites with magnetic resonance spectroscopy (MRS) provides a unique perspective on the brain bases of neuropsychiatric disorders. As a context for interpreting MRS studies of neuropsychiatric disorders, we review the characteristic MRS signals, the metabolic dynamics,and the neurobiological significance of the major brain metabolites that can be measured using clinical MRS systems. These metabolites include N-acetylaspartate(NAA), creatine, choline-containing compounds, myo-inositol, glutamate and glutamine, lactate, and gamma-amino butyric acid (GABA). For the major adult neuropsychiatric disorders (schizophrenia, bipolar disorder, major depression, and the anxiety disorders), we highlight the most consistent MRS findings, with an emphasis on those with potential clinical or translational significance. Reduced NAA in specific brain regions in schizophrenia, bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder corroborate findings of reduced brain volumes in the same regions. Future MRS studies may help determine the extent to which the neuronal dysfunction suggested by these findings is reversible in these disorders. Elevated glutamate and glutamine (Glx) in patients with bipolar disorder and reduced Glx in patients with unipolar major depression support models of increased and decreased glutamatergic function, respectively, in those conditions. Reduced phosphomonoesters and intracellular pH in bipolar disorder and elevated dynamic lactate responses in panic disorder are consistent with metabolic models of pathogenesis in those disorders. Preliminary findings of an increased glutamine/glutamate ratio and decreased GABA in patients with schizophrenia are consistent with a model of NMDA hypofunction in that disorder. As MRS methods continue to improve, future studies may further advance our understanding of the natural history of psychiatric illnesses, improve our ability to test translational models of pathogenesis, clarify therapeutic mechanisms of action,and allow clinical monitoring of the effects of interventions on brain metabolicmarkers

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Section: Naamentioning

confidence: 99%

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

Maddock

Buonocore

2011

Current Topics in Behavioral Neurosciences

226

196

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“…In the brain, NAT8L was shown to catalyze the formation of N-acetylaspartate (NAA) from acetyl-CoA and L-aspartate (14,15). NAA then acts as a carrier of acetyl groups between neurons and oligodendrocytes where NAA is catabolized by aspartoacylase into acetate and L-aspartate (16).…”

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confidence: 99%

NAT8L (N-Acetyltransferase 8-Like) Accelerates Lipid Turnover and Increases Energy Expenditure in Brown Adipocytes

Pessentheiner

Pelzmann

Walenta

et al. 2013

Journal of Biological Chemistry

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Background: NAT8L (N-acetyltransferase 8-like) synthesizes N-acetylaspartate and is required for myelination in the brain. Its function in other tissues was undefined. Results: Nat8l is highly expressed in adipose tissues and impacts adipogenic marker gene expression, lipid turnover, and energy metabolism in brown adipocytes. Conclusion: Nat8l expression influences cellular bioenergetics in adipocytes. Significance: These findings establish a novel pathway in brown adipocyte metabolism.

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“…Camello group of proteins in the pfam database are described as probable N-acetyltransferases (NAT) based on their sequence similarity to human Nat8 and Nat8l, which are reported to be aspartate acetyltransferases (AAT) specific to kidney and liver in human1415. Furthermore, Nat8 and Nat8l are shown to be localized to the secretary pathways primarily in the endoplasmic reticulum and display lysine acetyltransferase activity16.…”

Section: Resultsmentioning

confidence: 99%

Camello, a novel family of Histone Acetyltransferases that acetylate histone H4 and is essential for zebrafish development

Karmodiya

Anamika

Muley

et al. 2014

Sci Rep

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In this study, we have investigated genome-wide occurrence of Histone Acetyltransferases (HATs) in genomes of Mus musculus and Danio rerio on the basis of presence of HAT domain. Our study identified a group of proteins that lacks characteristic features of known HAT families, relatively smaller in size and has no other associated domains. Most of the proteins in this unclassified group are Camello proteins, which are not yet known and classified as functional HATs. Our in vitro and in vivo analysis revealed that Camello family proteins are active HATs and exhibit specificity towards histone H4. Interestingly, Camello proteins are among the first identified HATs showing perinuclear localization. Moreover, Camello proteins are evolutionarily conserved in all chordates and are observed for the first time in cnidarians in phylogeny. Furthermore, knockdown of Camello protein (CMLO3) in zebrafish embryos exhibited defects in axis elongation and head formation. Thus, our study identified a novel family of active HATs that is specific for histone H4 acetylation, exhibits perinuclear localization and is essential for zebrafish development.

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

Cited by 103 publications

References 52 publications

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

NAT8L (N-Acetyltransferase 8-Like) Accelerates Lipid Turnover and Increases Energy Expenditure in Brown Adipocytes

Camello, a novel family of Histone Acetyltransferases that acetylate histone H4 and is essential for zebrafish development

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