Acyl-coenzyme A synthetases in metabolic control.
OBJECTIVE
The 11 long-chain (ACSL) and very long chain acyl-coenzyme A (acyl-CoA) synthetases [(ACSVL)/fatty acid transport protein] are receiving considerable attention because it has become apparent that their individual functions are not redundant.


RESULTS
Recent studies have focused on the structure of the acyl-CoA synthetases, their post-translational modification, their ability to activate fatty acids of varying chain lengths, and their role in directing fatty acids into different metabolic pathways. An unsettled controversy focuses on the ACSVL isoforms and whether these have both enzymatic and transport functions. Another issue is whether conversion of a fatty acid to an acyl-CoA produces an increase in the AMP/ATP ratio that is sufficient to activate AMP-activated kinase.


CONCLUSIONS
Future studies are required to determine the subcellular location of each ACSL and ACSVL isoform and the functional importance of phosphorylation and acetylation. Purification and crystallization of mammalian ACSL and ACSVL isoforms is needed to confirm the mechanism of action and discover how these enzymes differ in their affinity for fatty acids of different chain lengths. Functionally, it will be important to learn how the ACSL isoforms can direct their acyl-CoA products toward independent downstream pathways.
Ellis
Jessica M
JM
Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
Frahm
Jennifer L
JL
Li
Lei O
LO
Coleman
Rosalind A
RA
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D003066:Coenzyme A Ligases / Q000737:chemistry / Q000378:metabolism*; D004194:Disease; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans
D005227:Fatty Acids; D055372:AMP-Activated Protein Kinases; D003066:Coenzyme A Ligases