Brain acetyl-CoA carboxylase: isozymic identification and studies of its regulation during development and altered...

Acetyl-CoA carboxylase, the rate-limiting enzyme of fatty acid synthesis, exists as an oligodendrocyte-associated enzyme in brain and plays an important role in supplying fatty acid for myelination. Rat brain acetyl-CoA carboxylase (ACC) has been identified as a single isozyme of M(r) = 265,000 daltons, indistinguishable immunologically from the isozyme in rat adipose tissue and liver. Total activity of brain ACC declines from birth to 4 weeks of age in the newborn rat. This change in activity can entirely be accounted for by changes in enzyme content, not enzyme specific activity, and is paralleled by decreases in ACC mRNA. In contrast, cardiac, skeletal muscle and liver ACC does not change in content over this developmental period. Unlike ACC in liver and adipose tissue, the enzyme content and specific activity of brain ACC is invariant during various states of nutrition. These data indicate that the brain ACC is subject to unique regulation, as compared to non-neural enzyme. The mechanisms underlying the control of neural ACC activity may be important to understanding the process of myelination during development and to a more general understanding of the factors regulating ACC expression/activity in other tissues.