Acetyl-CoA carboxylase in rat brain. I. Activities in homogenates and isolated fractions.

Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting and/or first committed step in fatty acid biosynthesis. Because fatty acids must be synthesized as components of the galactolipids and phospholipids in myelin, high specific activities of ACC would be expected in brain during myelination and in the myelinating cells, the oligondendroglia, in particular. Under reaction conditions where ACC was linear with time and protein concentration, we found specific activities of 1.7 and 3.1 nmol/min/mg protein in supernatants from forebrains and brainstems, respectively, of 20-day-old rats. In both regions, ACC declined during development, particularly after the age of 20 days. To separate forebrain into discrete fractions containing cells, membrane vesicles, and other components, without destroying the ACC, it was necessary to modify the published methods by adding citrate to the isolation medium and by omitting trypsin. A fraction which sedimented over 1.2 M sucrose showed the highest specific activities and recoveries of ACC. This fraction was rich in small cells, many of which immunostained with antibodies against galactocerebroside and carbonic anhydrase, both of which are localized in oligodendrocytes and immature glial cells. The cells in this fraction also immunostained with antibodies against ACC. The results are consistent with the hypothesis that ACC is an oligodendrocyte-associated enzyme, although it probably is not exclusive to cells of that type.