Hartman EJ, Omura S, Laposata M.Triacsin C: a differential
inhibitor of arachidonoyl-CoA synthetase and nonspecific long
chain acyl-CoA synthetase.
Prostaglandins. 1989 Jun;37(6):655-71.
Dept. of Pathology and Laboratory Medicine, Hospital of the
University of Pennsylvania, Philadelphia 19104.
Triacsins A, B, C, and D are newly discovered compounds isolated
from the culture filtrate of streptomyces which are known to
inhibit nonspecific long chain acyl-CoA synthetase (EC
6.2.1.3.). These inhibitors have not been previously studied
with regard to their effects on arachidonoyl-CoA synthetase, an
enzyme which specifically utilizes arachidonate and other
icosanoid precursor fatty acids. To explore this question, we
used triacsin C, a potent inhibitor of the nonspecific acyl-CoA
synthetase. Triacsin C was found to inhibit the action of
arachidonoyl-CoA synthetase and the nonspecific enzyme in
sonicates of HSDM1C1 mouse fibrosarcoma cells. Importantly,
however, the triacsin concentration and length of pre-incubation
with the enzymes could be adjusted to almost completely inhibit
(greater than 80%) the nonspecific long chain acyl
CoA-synthetase, with less than 20% inhibition of
arachidonoyl-CoA synthetase. Using intact cultured cells exposed
to 1 ug/ml triacsin for up to 15 minutes, we unexpectedly
observed preferential inhibition of arachidonoyl-CoA synthetase
activity. In intact cell studies, arachidonoyl-CoA synthetase
was inhibited greater than 90%, with 55-60% inhibition of the
nonspecific acyl-CoA synthetase. As additional evidence of its
inhibition of acyl-CoA synthetase enzymes in intact cells,
triacsin C inhibited both fatty acid uptake into cells and
icosanoid production, metabolic processes which in certain cell
types appear to be dependent on acyl-CoA synthetase activity.
Thus, triacsin C is a novel inhibitor which can alter the fatty
metabolism of intact cells. This compound can be of significant
value in determining the specific cellular functions of the two
acyl-CoA synthetase enzymes.
PMID: 2505330
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