Acyl-CoAs are functionally channeled in liver: potential role of acyl-CoA synthetase

Acyl-CoA synthetase (ACS) catalyzes the activation of long-chain fatty acid s to acyl-CoAs, which can be metabolized to form CO2, triacylglycerol (TAG) , phospholipids (PL), and cholesteryl esters (CE). To determine whether inh ibiting ACS affects these pathways differently, we incubated rat hepatocyte s with [C-14] oleate and the ACS inhibitor triacsin C. Triacsin inhibited T AG synthesis 70% in hepatocytes from fed rats and 40% in starved rats, but it had little effect on oleate incorporation into CE, PL, or beta -oxidatio n end products. Triacsin blocked [H-3] glycerol incorporation into TAG and PL 33 and 25% more than it blocked [C-14] oleate incorporation, suggesting greater inhibition of de novo TAG synthesis than reacylation. Triacsin did not affect oxidation of prelabeled intracellular lipid. ACS1 protein was ab undant in liver microsomes but virtually undetectable in mitochondria. Refe eding increased microsomal ACS1 protein 89% but did not affect specific act ivity. Triacsin inhibited ACS specific activity in microsomes more from fed than from starved rats. These data suggest that ACS isozymes may be functi onally linked to specific metabolic pathways and that ACS1 is not associate d with beta -oxidation in liver.