Do long-chain acyl-CoA synthetases regulate fatty acid entry into synthetic versus degradative pathways?
Recent studies suggest that the long-chain acyl-CoA synthetases (ACS) may play a role in channeling fatty acids either toward complex lipid synthesis and storage or toward oxidation. Each of the five members of the ACS family that has been cloned has a distinct tissue distribution and subcellular location, and is regulated independently during cellular differentiation and by diverse hormones and nuclear transcription factors including adrenocorticotropic hormone (ACTH), peroxisomal proliferator-activated receptor-alpha (PPARalpha) and sterol regulatory element binding protein. Taken as a whole, these features suggest that in liver, ACS1 and ACS5 may provide acyl-CoA destined primarily for triacylglycerol synthesis or for mitochondrial oxidation, respectively. ACS4 may provide acyl-CoA for both synthesis and peroxisomal oxidation, depending on whether the enzyme is associated with the mitochondrial-associated membrane or with peroxisomes. It should be emphasized that although the data for acyl-CoA channeling are strong, they are indirect. Rigorous testing of these predictions will be required.
Coleman
Rosalind A
RA
University of North Carolina, Chapel Hill, 27599-7461, USA. rcoleman@unc.edu
Lewin
Tal M
TM
Van Horn
Cynthia G
CG
Gonzalez-Baró
Maria R
MR
D000818:Animals; D003066:Coenzyme A Ligases / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000096:biosynthesis / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009747:Nutritional Physiological Phenomena; D013379:Substrate Specificity
D005230:Fatty Acids, Nonesterified; D007527:Isoenzymes; D003066:Coenzyme A Ligases