To understand the role of N-acetylaspartate (NAA) as an acetyl donor,
we investigated the metabolism of NAA in brain and liver slice prepara
tions. The tissue slices were incubated with [C-14-acetyl]NAA (SA = 3
mu Ci/mu mol) or [C-14]acetate (SA = 3 mu Ci/mu mol) for 2 h. The tiss
ue was homogenized and was extracted using chloroform/methanol (2:1).
The aqueous phase was initially analyzed using anion exchange HPLC whi
le the lipid phase was analyzed using a two-dimensional TLC system. Fu
rther resolution of the NAA peak from the anion exchange HPLC was perf
ormed using a reverse phase HPLC system. The aqueous phase of both the
river and brain samples incubated with [C-14-acetyl]NAA revealed simi
lar patterns of three distinct radioactivity peaks corresponding to NA
A, acetate and an early eluting unknown molecule. Further resolution o
f the NAA peak using reverse phase HPLC indicated that it corresponded
to NAA and acetyl CoA. There was significant incorporation of radioac
tivity into various lipid components in both the brain and liver sampl
es. Patterns similar to that observed with NAA were detected in the ca
se of [C-14]acetate in both the brain and liver slice preparations. Th
ese results demonstrate that NAA metabolism is not restricted to the n
ervous system, although its biosynthesis is. It is clear that acetyl m
oiety of NAA is incorporated into lipids and partially hydrolyzed to f
ree acetate in both brain and liver preparations. Further, production
of acetyl CoA from NAA indicates that the acetyl group of NAA is incor
porated into lipids and perhaps other acetylated molecules via the ace
tyl CoA route. A working hypothesis on the metabolic role of NAA is pr
esented.