Long-chain acyl-CoA synthetase isoforms differ in preferences for eicosanoid species and long-chain fatty acids[S]

Journal of Lipid Research

卷:58

Shufen Chen¹  Alekhya Yechoor²  Rosalind A. Coleman²  Fred B. Lih³  Eric L. Klett⁴ 

[1] Department of Medicine, Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, NC 27599;

[2] Department of Nutrition, University of North Carolina School of Public Health, Chapel Hill, NC 27599;

[3] To whom correspondence should be addressed.;

关键词: arachidonic acid;    cytochrome P450;    fatty acid/metabolism;    phospholipids;    acyl-coenzyme A;   

DOI  :  

来源: DOAJ

【 摘 要 】

Because the signaling eicosanoids, epoxyeicosatrienoic acids (EETs) and HETEs, are esterified to membrane phospholipids, we asked which long-chain acyl-CoA synthetase (ACSL) isoforms would activate these molecules and whether the apparent FA substrate preferences of each ACSL isoform might differ depending on whether it was assayed in mammalian cell membranes or as a purified bacterial recombinant protein. We found that all five ACSL isoforms were able to use EETs and HETEs as substrates and showed by LC-MS/MS that ACSLs produce EET-CoAs. We found differences in substrate preference between ACS assays performed in COS7 cell membranes and recombinant purified proteins. Similarly, preferences and Michaelis-Menten kinetics for long-chain FAs were distinctive. Substrate preferences identified for the purified ACSLs did not correspond to those observed in ACSL-deficient mouse models. Taken together, these data support the concept that each ACSL isoform exhibits a distinct substrate preference, but apparent substrate specificities depend upon multiple factors including membrane character, coactivators, inhibitors, protein interactions, and posttranslational modification.

【 授权许可】

Unknown