ACETOACETATE AND <scp>d</scp>‐(‐)‐BETA‐HYDROXYBUTYRATE AS PRECURSORS FOR STEROL SYNTHESIS BY CALF OLIGODENDROCYTES IN SUSPENSION CULTURE: EXTRAMITOCHONDRIAL PATHWAY FOR ACETOACETATE METABOLISM

Pleasure, David E; Lichtman, Craig; Eastman, Sarah T.; Lieb, Marge; Abramsky, Oded; Silberberg, Donald H.

doi:10.1111/j.1471-4159.1979.tb11083.x

Cited by 46 publications

(21 citation statements)

References 22 publications

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“…We expected to find that acetoacetate was more cholesterogenic than glucose, especially in oligodendrocytes, because of a cytosolic acetoacetylCoA synthetase [12-141 and its enrichment in oligodendrocytes [17]. However, to our surprise, we did not find preferential incorporation of [3-"C]acetoacetate into cholesterol, when compared to [U-'4C]glucose as substrate.…”

Section: Wimentioning

confidence: 63%

Acetoacetate and glucose as substrates for lipid synthesis by rat brain oligodendrocytes and astrocytes in serum-free culture

Koper

Zeinstra

Lopes‐Cardozo

et al. 1984

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metaboli

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Section: Wimentioning

confidence: 63%

Acetoacetate and glucose as substrates for lipid synthesis by rat brain oligodendrocytes and astrocytes in serum-free culture

Koper

Zeinstra

Lopes‐Cardozo

et al. 1984

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metaboli

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“…Oligodendrocytes in the brain may also make use of a similar alternate pathway of acetyl CoA production involving free acetate. Indeed, a citrate lyase independent pathway of acetate incorporation into sterols has been reported in calf brain oligodendrocytes in culture (Pleasure et al, 1979).…”

Section: Unique Aspects Of Cns Lipid Metabolismmentioning

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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“…1 and 2). Although the metabolism of these ketone bodies by in vivo and in vitro brain preparations has been investigated, very little is known about their metabolism by neuronal and glial cells (3)(4)(5). Because pure preparations ofglial and neuronal cells are difficult to obtain and to maintain in culture, established lines of glial and neuronal origin have been widely used as representatives of these cell types (6).…”

mentioning

confidence: 99%

Ketone-body metabolism in glioma and neuroblastoma cells.

Patel¹,

Russell²,

Gershman³

1981

Proc. Natl. Acad. Sci. U.S.A.

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We have examined the metabolism of ketone bodies in neuroblastoma C1300 and glioma C6 cells, two established lines of neural origin. The three ketone body-metabolizing enzymes are present in cells of both lines in the relative proportions normally found in brain (D-3-hydroxybutyrate dehydrogenase < acetoacetyl-CoA thiolase < 3-ketoacid CoA-transferase), the activities of the first two are higher in glioma cells than in neuroblastoma, and that ofthe third is 2-fold higher in neuroblastoma cells than in glioma cells. The specific activity of 3-ketoacid CoAtransferase (EC 2.8.3.5) in both cell lines increased as the cultures achieved confluence, then decreased. Ketone bodies and especially acetoacetate are preferred substrates for synthesis of neural lipids in cells ofboth lines. The incorporation ofglucose carbon into lipids is significantly reduced in cells ofboth lines in the presence of ketone bodies. Addition of acetoacetate but not DL-3-hydroxybutyrate to the culture medium resulted in a significant increase in the activity of 3-ketoacid CoA-transferase and also in the rate of acetoacetate oxidation in neuroblastoma cells but not glioma cells. These findings indicate that specific differences exist in the capacity of these two cell lines to metabolize ketone bodies and also that substrate-level regulation of the ketone body-metabolizing pathway exists. These two lines therefore provide a potentially useful system in which the mechanisms of regulation ofthese enzymes may be examined.The importance of acetoacetate (AcAcO) and D-3-hydroxybutyrate (D-3-HB) as fuels for cerebral metabolism and as precursors for lipid synthesis in developing rat brain has been well documented (for review see refs. 1 and 2). Although the metabolism of these ketone bodies by in vivo and in vitro brain preparations has been investigated, very little is known about their metabolism by neuronal and glial cells (3)(4)(5). Because pure preparations ofglial and neuronal cells are difficult to obtain and to maintain in culture, established lines of glial and neuronal origin have been widely used as representatives of these cell types (6). Even after transformation, these clonal cell lines retain many of their characteristic metabolic pathways (7,8).The present study was, therefore, initiated to investigate possible differences in the metabolism of ketone bodies between two established clonal cell lines, namely glioma C6 and neuroblastoma C1300 (N2a). The results show that there are specific differences between these two cell lines of glial and neuronal origin with respect to their capacities to metabolize ketone bodies and in their regulation by exposure to ketone bodies. MATERIALS AND METHODSCell Culture. Rat glioma C6 and mouse neuroblastoma C1300 (N2a) clones were maintained in Eagle's minimal essential medium containing 4-fold increased concentrations ofamino acids and vitamins, and supplemented with 10% fetal calf serum, penicillin at 100 units/ml, and streptomycin at 100 pZg/ ml. The medium also contained 5 mM glucose and 2 m...

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ACETOACETATE AND d‐(‐)‐BETA‐HYDROXYBUTYRATE AS PRECURSORS FOR STEROL SYNTHESIS BY CALF OLIGODENDROCYTES IN SUSPENSION CULTURE: EXTRAMITOCHONDRIAL PATHWAY FOR ACETOACETATE METABOLISM

Cited by 46 publications

References 22 publications

Acetoacetate and glucose as substrates for lipid synthesis by rat brain oligodendrocytes and astrocytes in serum-free culture

Acetoacetate and glucose as substrates for lipid synthesis by rat brain oligodendrocytes and astrocytes in serum-free culture

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Ketone-body metabolism in glioma and neuroblastoma cells.

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