ACETATE METABOLISM IN THE NERVOUS SYSTEM. <i>N</i>‐ACETYL‐<scp>l</scp>‐ASPARTIC ACID AND THE BIOSYNTHESIS OF BRAIN LIPIDS*

D’Adamo, Amedeo F.; Yatsu, Frank M.

doi:10.1111/j.1471-4159.1966.tb10292.x

Cited by 157 publications

(91 citation statements)

References 17 publications

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“…White matter pathology in rodent models, such as the ASPA-null knockout mouse, was shown to involve myelin vacuolization as a feature of dysmyelination and/or demyelination [5]. Those findings were consistent with previous reports suggesting a vital role for ASPA and its NAA substrate in myelination, including the finding of incorporation of the acetyl component of NAA into brain-and myelin lipids [6][7][8]. This concept was extended in a subsequent study showing that NAA localized in the neuron/axon contributed acetyl groups that were incorporated into ensheathing myelin lipids [9].…”

Section: Introductionsupporting

confidence: 91%

“…This is based on studies showing incorporation of the acetyl group of NAA into brain lipids [6][7][8] and in particular into lipids of myelin itself from intraneuronal NAA [9]. The latter report also demonstrated the presence of ASPA in highly purified myelin, and a subsequent study showed bimodal occurrence of this enzyme in myelin and cytosol [14].…”

Section: Discussionmentioning

confidence: 96%

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Myelin Lipid Abnormalities in the Aspartoacylase-Deficient Tremor Rat

Wang

Leone

et al. 2008

Neurochem Res

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The high concentration of N-acetylaspartate (NAA) in neurons of the central nervous system and its growing clinical use as an indicator of neuronal viability has intensified interest in the biological function of this amino acid derivative. The biomedical relevance of such inquiries is highlighted by the myelin-associated pathology of Canavan disease, an inherited childhood disorder resulting from mutation of aspartoacylase (ASPA), the NAA-hydrolyzing enzyme. This enzyme is known to be localized in oligodendrocytes with bimodal distribution in cytosol and the myelin sheath, and to produce acetyl groups utilized in myelin lipid synthesis. Loss of this acetyl source in Canavan disease and rodent models such as the tremor rat are thought to account for the observed myelin deficit. This study was undertaken to further define and quantify the specific lipid abnormalities that occur as a result of ASPA deficit in the tremor rat. Employing mass spectrometry together with high performance thin-layer chromatography, we found that myelin from 28-day-old animals showed major reduction in cerebrosides (CB) and sulfatides (Sulf) with unsubstituted fatty acids, and equal if not greater changes in myelin from 7-month-old tremors. Cerebrosides with 2-hydroxyfatty acids showed little if any change at either age; Sulf with 2-hydroxyfatty acids showed no significant change at 28 days, but surprisingly a major increase at 7 months. Two species of phosphatidylcholine, 32:0 and 34:1, also showed significant increase, but only at 28 days. One form of phosphatidylethanolamine, PE36:1, was reduced a modest amount at both ages, whereas the plasmalogen form did not change. The dysmyelination that results from inactivation of ASPA is thus characterized by selective decreases as well as some increases in specific lipids.

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Section: Introductionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Myelin Lipid Abnormalities in the Aspartoacylase-Deficient Tremor Rat

Wang

Leone

et al. 2008

Neurochem Res

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“…Astroglia have transporters that import NAA specifically (13), and neurons take up very little NAA (14). Aspartoacylase, which catalyzes the degradation of NAA, is expressed primarily in white matter tracts and oligodendrocytes (15), which is consistent with earlier reports that NAA is associated with myelination and mitochondrial membranes (16,17). These reports are consistent with a scenario in which NAA is synthesized in neurons in a process related to cellular energetics, released slowly to the extracellular environment, and degraded to aspartate and acetyl moieties in glia.…”

Section: N-acetyl Aspartate (Naa)supporting

confidence: 90%

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

Mason

Krystal

2006

NMR Biomed.

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Magnetic resonance spectroscopy (MRS) is likely in the near future to play a key role in the process of drug discovery and evaluation. As the pharmaceutical industry seeks biochemical markers of drug delivery, efficacy and toxicity, this non-invasive technique offers numerous ways to study adults and children repeatedly and without ionizing radiation. In this article, we survey an array of the information that MRS offers about neurochemistry in general and psychiatric disorders and their treatment in particular. We also present growing evidence of glial abnormalities in neuropsychiatric disorders and discuss what MRS is contributing to that line of investigation. The third major direction of this article is the discussion of where MRS techniques are headed and how those new techniques can contribute to studies of mechanisms of psychiatric disease and drug discovery.

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“…21 This compound serves as an active acetyl donor in the synthesis of brain lipids, thus participating in the myelination process. 22 - 23 NAA was not found in the CSF of normal subjects, nor was it detected in CSF from patients with MS in this study.…”

Section: Discussionmentioning

confidence: 64%

Nuclear Magnetic Resonance Study of Cerebrospinal Fluid From Patients With Multiple Sclerosis

Lynch

Peeling

Auty

et al. 1993

Can. j. neurol. sci.

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Proton nuclear magnetic resonance (NMR) spectroscopy was used to examine cerebrospinal fluid (CSF) from patients (n = 30) with actively progressive multiple sclerosis (MS). Metabolite concentrations obtained from the spectra were compared to those determined from the spectra of CSF from control patients (n = 27) with benign spinal disorders. No significant difference was found between the 2 groups for most constituents, including lactate, glutamine, citrate, creatine and creatinine, and glucose. Acetate levels were significantly higher in MS patients, while formate levels were significantly lower, than the controls. There were no significant differences in metabolite concentrations in CSF from early and longstanding MS patients. A peak due to an unidentified compound was found at 2.82 ppm in the spectra of CSF from patients with actively progressive MS, but not in the spectra of CSF from the controls. The peak was not found in spectra of CSF from patients with AIDS dementia complex (n = 9) or Parkinson's disease (n = 5), but it did appear in spectra of CSF from 1 patient with Jakob-Creutzfeldt disease (out of 3 examined) and from 1 patient (out of 7) with Guillan-Barre disease. The unidentified compound is volatile and, from the chemical shift of the observed NMR peak, is probably an N-methyl compound. As such, it may be an intermediate in the cholinoglycine cycle, in which an abnormality has been proposed to exist in MS patients. RESUME: Etude par resonance magnetique nucleaire du liquide cephalo-rachidien de patients atteints de sclerose en plaques. Nous avons utilise la spectroscopie par resonance magnetique nucleaire pour examiner le liquide cephalo-rachidien (LCR) de patients (n = 30) atteints de sclerose en plaques (SEP) en phase active. Les concentrations de certains metabolites, obtenues a partir du spectre, etaient comparees a celles obtenues du spectre du LCR de patients controles (n = 27) ayant des affections spinales benignes. II n'y avait pas de difference significative entre les deux groupes pour la plupart des metabolites, incluant le lactate, la glutamine, le citrate, la creatine et la creatinine, ainsi que le glucose. Les niveaux d'acetate etaient significativement plus eleves dans la SEP, alors que les niveaux de formate etaient significativement plus bas que ceux des controles. II n'y avait pas de difference significative dans les concentrations de metabolites dans le LCR des patients avec SEP au debut de la maladie par rapport a ceux qui etaient atteints depuis longtemps. Un pic du a un compose non identifie a ete observe a 2.82 ppm dans le spectre du LCR des patients en phase active de la SEP. Ce pic n'etait pas present dans le spectre du LCR des controles ou dans celui du LCR de patients atteints du complexe SIDA-demence (n = 9) ou de la maladie de Parkinson (n = 5). Cependant il etait present dans le spectre du LCR d'un patient atteint de la maladie de Jakob-Creutzfeldt (sur 3 patients examines) et d'un patient atteint du syndrome de Guillain-Barre (sur 7 patients examines). Le c...

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ACETATE METABOLISM IN THE NERVOUS SYSTEM. N‐ACETYL‐l‐ASPARTIC ACID AND THE BIOSYNTHESIS OF BRAIN LIPIDS*

Cited by 157 publications

References 17 publications

Myelin Lipid Abnormalities in the Aspartoacylase-Deficient Tremor Rat

Myelin Lipid Abnormalities in the Aspartoacylase-Deficient Tremor Rat

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

Nuclear Magnetic Resonance Study of Cerebrospinal Fluid From Patients With Multiple Sclerosis

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