ACETYL TRANSPORT MECHANISMS IN THE NERVOUS SYSTEM. THE OXOGLUTARATE SHUNT AND FATTY ACID SYNTHESIS IN THE DEVELOPING RAT BRAIN^*

Abstract

Radioactive acetyl groups and lipids are produced from dl‐[5‐14C]glutamate. Degradation studies indicate that approximately 90 per cent of the radioactivity is localized in the original carboxyl groups of the two carbon unit. Since these results are shown not to be due to a 14CO2 fixation, it is concluded that the oxoglutarate shunt as an acetyl group transport system is functional in brain. The highest ratio of fatty’acid activity/CO2 activity in this pathway is found in the newborn rat brain and steadily decreases with development. This pattern is observed with incubations of brain slices with labelled glutamate or citrate and is similar to the changes observed in the activity of the citrate cleavage enzyme with brain maturation. In contrast to the previous studies with liver preparations, the conversion of [2‐14C]‐ and [5‐14C]glutamate to fatty acids is relatively small. This is particularly true during the period of maximal lipid synthesis.

Regional and Subcellular Distribution of ATP‐Citrate Lyase and Other Enzymes of Acetyl‐CoA Metabolism in Rat Brain

“…The activities of CCE, reported here, are of the same magnitude as those reported for cytosol of rat brain and chick embryo brain (Srere, 1959;Szutowicz et al, 1974;1976a;1977) (Tables 1 and 7). They are, however, 5 to 30 times higher than CCE activities reported by other authors (TuCek, 1967a,b;D'Adamo and D'Adamo, 1968;Smith et al, 1970) (Table 7). These contradictions may result from the differences in the assay procedure.…”

N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase

“…The rescue of AcCoA, MalCoA, and ATP by AAV-Olig001-ASPA in nur7 mice provides evidence for NAA catabolism contributing to both myelination and oxidative metabolism, and suggests NAA acts as an energy shuttle from the axon to the oligodendrocyte, thereby building on a theme of neuro-glia metabolic coupling. Glycolytic AcCoA contributes to myelin lipid synthesis, with a portion of this requisite substrate provided to oligodendroglia in the form of NAA(D’Adamo and D’Adamo, 1968) (Burri et al, 1991). In the absence of NAA, the resultant diversion of glucose-derived AcCoA to fatty acid synthesis is hypothesized to result in a net loss of ATP (Harris and Attwell, 2012).…”

“…NAA has multiple hypothesized functions as an osmolyte (Baslow, 2003; Taylor et al, 1995), a building block for myelin synthesis(Chakraborty et al, 2001; Madhavarao et al, 2005; Mehta and Namboodiri, 1995), a metabolic intermediate(D’Adamo and D’Adamo, 1968) (Mehta and Namboodiri, 1995), and developmental signal molecule(Francis et al, 2006). Based on these diverse roles, it follows that the effects of dysregulated NAA in Canavan disease are likely multi-factorial.…”

Effect of Free Malonate on the Utilization of Glutamate by Rat Brain Mitochondria

“…However, the lack of stoichiometric recovery of 2-oxoglutarate in the presence of arsenite is more difficult to explain. Reductive carboxylation to isocitrate is at least a theoretical possibility (D'Adamo and DAdamo, 1968;Patel and Tilghman, 1973;Patel, 1974) but was not specifically studied here.…”