Fatty acid transport by vectorial acylation in mammals: roles played by different isoforms of rat long-chain acyl-CoA synthetases.
Mammals express multiple isoforms of acyl-CoA synthetase (ACSL1 and ACSL3-6) in various tissues. These enzymes are essential for fatty acid metabolism providing activated intermediates for complex lipid synthesis, protein modification, and beta-oxidation. Yeast in contrast express four major ACSLs, which have well-defined functions. Two, Faa1p and Faa4p, are specifically required for fatty acid transport by vectorial acylation. Four ACSLs from the rat were expressed in a yeast faa1delta faa4delta strain and their roles in fatty acid transport and trafficking characterized. All four restored ACS activity yet varied in substrate preference. ACSL1, 4, and 6 were able to rescue fatty acid transport activity and triglyceride synthesis. ACSL5, however, was unable to facilitate fatty acid transport despite conferring robust oleoyl-CoA synthetase activity. This is the first study evaluating the role of the mammalian ACSLs in fatty acid transport and supports a role for ACSL1, 4, and 6 in transport by vectorial acylation.
Tong
Fumin
F
Center for Metabolic Disease, Ordway Research Institute and Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208-3425, USA.
Black
Paul N
PN
Coleman
Rosalind A
RA
DiRusso
Concetta C
CC
D000215:Acylation; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D003066:Coenzyme A Ligases / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
D005227:Fatty Acids; D007527:Isoenzymes; D011994:Recombinant Proteins; D003066:Coenzyme A Ligases