Acyl-CoAs are functionally channeled in liver: potential role of acyl-CoA synthetase.
Acyl-CoA synthetase (ACS) catalyzes the activation of long-chain fatty acids to acyl-CoAs, which can be metabolized to form CO(2), triacylglycerol (TAG), phospholipids (PL), and cholesteryl esters (CE). To determine whether inhibiting ACS affects these pathways differently, we incubated rat hepatocytes with [(14)C]oleate and the ACS inhibitor triacsin C. Triacsin inhibited TAG 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-oxidation end products. Triacsin blocked [(3)H]glycerol incorporation into TAG and PL 33 and 25% more than it blocked [(14)C]oleate incorporation, suggesting greater inhibition of de novo TAG synthesis than reacylation. Triacsin did not affect oxidation of prelabeled intracellular lipid. ACS1 protein was abundant in liver microsomes but virtually undetectable in mitochondria. Refeeding increased microsomal ACS1 protein 89% but did not affect specific activity. Triacsin inhibited ACS specific activity in microsomes more from fed than from starved rats. These data suggest that ACS isozymes may be functionally linked to specific metabolic pathways and that ACS1 is not associated with beta-oxidation in liver.
Muoio
D M
DM
Departments of Nutrition and Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7400, USA.
Lewin
T M
TM
Wiedmer
P
P
Coleman
R A
RA
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002250:Carbon Radioisotopes; D003066:Coenzyme A Ligases / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005215:Fasting / Q000502:physiology; D005990:Glycerol / Q000493:pharmacokinetics; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D019301:Oleic Acid / Q000493:pharmacokinetics; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014226:Triazenes / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D014316:Tritium
D000214:Acyl Coenzyme A; D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D014226:Triazenes; D014280:Triglycerides; D014316:Tritium; D019301:Oleic Acid; C034613:triacsin C; D003066:Coenzyme A Ligases; D005990:Glycerol