Labeling of N-acetylaspartate and N-acetylaspartylglutamate in rat neocortex, hippocampus and cerebellum from [1-13C]glucose

Tyson, Randy L.; Sutherland, Garnette R.

doi:10.1016/s0304-3940(98)00527-8

Cited by 47 publications

(38 citation statements)

References 20 publications

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“…In extract studies, the water soluble metabolites are extracted from tissues, and subsequent MRS measurements of the extracts allow not only identification of various compounds within the tissue samples, but also identification of the intramolecular positions of the labeled atomic nuclei on the basis of their chemical shift. Tyson and Sutherland have used this approach to study the labeling of NAA and NAAG after infusion of [1-13 C] glucose in rats, followed by dissection and homogenization of samples from cerebellum, cerebral cortex and hippocampus (Tyson and Sutherland, 1998). Their studies showed that label was incorporated into NAA from labeled acetate (acetyl CoA) and from labeled aspartate, while NAAG was labeled from labeled glutamate.…”

Section: Naa Synthesismentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,229

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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Section: Naa Synthesismentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,229

1,126

View full text Add to dashboard Cite

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“…A controlled post mortem study in schizophrenia reported an abnormal increase of NAAG and a reduction of N-acetyl-alpha-linked acidic dipeptidase (NAALADase, the enzyme responsible for the cleavage of NAAG into NAA and glutamate), mainly in the hippocampus and prefrontal cortex . On the other hand, NAAG itself is synthesized from NAA and glutamate, mediated by N-acetylaspartate-L-glutamate ligase (Tyson and Sutherland, 1998). In this step, NAA availability may have a stimulating effect on the synthesis rate of NAAG (Gehl et al, 2004;Tsai, 2005).…”

Section: Interaction Of Hippocampal Naa and Volumementioning

confidence: 99%

“…NAA is suggested to be a marker of neuronal integrity and an indicator for the number of viable neurons (Bertolino and Weinberger, 1999;Lang et al, 2007a). However, in schizophrenia research it was less considered that NAA-the second most abundant amino acid in the human brain-is involved in the metabolism of neurotransmitters, such as N-acetyl-aspartyl-glutamate (NAAG), aspartate and glutamate (Tsai, 2005;Tyson and Sutherland, 1998). For instance, NAA is synthesized by cleavage from NAAG by N-acetylated alpha-linked L-amino dipeptidase (also termed glutamate carboxypeptidase II) with one molecule glutamate as co-product.…”

Section: Introductionmentioning

confidence: 99%

Interaction of hippocampal volume and N-acetylaspartate concentration deficits in schizophrenia: A combined MRI and 1H-MRS study

et al. 2010

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“…Using 13 C-labeled glucose infusions and 13 C-MRS of tissue extracts from several brain regions Tyson and Sutherland (1998) found the incorporation rate into labeled NAA was relatively low as compared with the labeling of glutamate, or the neuronal dipeptide N -acetylaspartylglutamate (NAAG). In this study the fractional enrichment of NAA after a 200 min 13 C-glucose infusion was 3%, whereas the fractional enrichment of NAAG was 20% and that of glutamate 25.2%, indicating that in the uninjured adult rat brain the turnover of NAA was relatively slow.…”

Section: Introductionmentioning

confidence: 99%

N-Acetylaspartate reductions in brain injury: impact on post-injury neuroenergetics, lipid synthesis, and protein acetylation

Moffett

Arun

Ariyannur

et al. 2013

Front. Neuroenergetics

152

135

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N-Acetylaspartate (NAA) is employed as a non-invasive marker for neuronal health using proton magnetic resonance spectroscopy (MRS). This utility is afforded by the fact that NAA is one of the most concentrated brain metabolites and that it produces the largest peak in MRS scans of the healthy human brain. NAA levels in the brain are reduced proportionately to the degree of tissue damage after traumatic brain injury (TBI) and the reductions parallel the reductions in ATP levels. Because NAA is the most concentrated acetylated metabolite in the brain, we have hypothesized that NAA acts in part as an extensive reservoir of acetate for acetyl coenzyme A synthesis. Therefore, the loss of NAA after TBI impairs acetyl coenzyme A dependent functions including energy derivation, lipid synthesis, and protein acetylation reactions in distinct ways in different cell populations. The enzymes involved in synthesizing and metabolizing NAA are predominantly expressed in neurons and oligodendrocytes, respectively, and therefore some proportion of NAA must be transferred between cell types before the acetate can be liberated, converted to acetyl coenzyme A and utilized. Studies have indicated that glucose metabolism in neurons is reduced, but that acetate metabolism in astrocytes is increased following TBI, possibly reflecting an increased role for non-glucose energy sources in response to injury. NAA can provide additional acetate for intercellular metabolite trafficking to maintain acetyl CoA levels after injury. Here we explore changes in NAA, acetate, and acetyl coenzyme A metabolism in response to brain injury.

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Labeling of N-acetylaspartate and N-acetylaspartylglutamate in rat neocortex, hippocampus and cerebellum from [1-13C]glucose

Cited by 47 publications

References 20 publications

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Interaction of hippocampal volume and N-acetylaspartate concentration deficits in schizophrenia: A combined MRI and 1H-MRS study

N-Acetylaspartate reductions in brain injury: impact on post-injury neuroenergetics, lipid synthesis, and protein acetylation

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