Igal RA, Wang P, Coleman RA.Triacsin C blocks de novo
synthesis of glycerolipids and cholesterol esters but not
recycling of fatty acid into phospholipid: evidence for
functionally separate pools of acyl-CoA.
Biochem J. 1997 Jun 1;324 ( Pt 2):529-34.
Departments of Nutrition and Pediatrics, University of North
Carolina at Chapel Hill, Chapel Hill, NC 27599-7400, USA.
The trafficking of acyl-CoAs within cells is poorly understood.
In order to determine whether newly synthesized acyl-CoAs are
equally available for the synthesis of all glycerolipids and
cholesterol esters, we incubated human fibroblasts with
[14C]oleate, [3H]arachidonate or [3H]glycerol in the presence or
absence of triacsin C, a fungal metabolite that is a competitive
inhibitor of acyl-CoA synthetase. Triacsin C inhibited de novo
synthesis from glycerol of triacylglycerol, diacylglycerol and
cholesterol esters by more than 93%, and the synthesis of
phospholipid by 83%. However, the incorporation of oleate or
arachidonate into phospholipids appeared to be relatively
unimpaired when triacsin was present. Diacylglycerol
acyltransferase and lysophosphatidylcholine acyltransferase had
similar dependences on palmitoyl-CoA in both liver and
fibroblasts; thus it did not appear that acyl-CoAs, when present
at low concentrations, would be preferentially used to acylate
lysophospholipids. We interpret these data to mean that, when
fatty acid is not limiting, triacsin blocks the acylation of
glycerol 3-phosphate and diacylglycerol, but not the reacylation
of lysophospholipids. Two explanations are possible: (1)
different acyl-CoA synthetases exist that vary in their
sensitivity to triacsin; (2) an independent mechanism channels
acyl-CoA towards phospholipid synthesis when little acyl-CoA is
available. In either case, the acyl-CoAs available to acylate
cholesterol, glycerol 3-phosphate, lysophosphatidic acid and
diacylglycerol and those acyl-CoAs that are used by
lysophospholipid acyltransferases and by ceramide
N-acyltransferase must reside in two non-mixing acyl-CoA pools
or, when acyl-CoAs are limiting, they must be selectively
channelled towards specific acyltransferase reactions.
PMID: 9182714
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