title: Acyl coenzyme a synthetase regulation: putative role in long-chain acyl coenzyme a partitioning.
abstract: OBJECTIVE
  Long-chain acyl coenzyme A synthetase (ACSL) converts free fatty acids (FFAs) into their metabolizable long-chain acyl coenzyme A (LC-CoA) derivatives that are essential for FFA conversion to CO(2), triglycerides, or complex lipids. ACSL-1 is highly expressed in adipose tissue with broad substrate specificity. We tested the hypothesis that ACSL localization, and resulting local generation of LC-CoA, regulates FFA partitioning.
  
  
  METHODS
  These studies used cell fractionation of rat adipocytes to measure ACSL activity and mass and compared cells from young, mature, fed, fasted, and diabetic rats. Functional studies included measurement of FFA oxidation, complex lipid synthesis, and LC-CoA levels.
  
  
  RESULTS
  High ACSL specific activity was expressed in the mitochondria/nuclei (M/N), high-density microsomes (HDM), low-density microsomes (LDM), and plasma membrane (PM) fractions. We show here that, during fasting, total FFA oxidation increased, and, although total ACSL activity decreased, a greater percentage of activity (43 +/- 1.5%) was associated with the M/N fraction than in the fed state (23 +/- 0.3%). In the fed state, more ACSL activity (34 +/- 0.5%) was associated with the HDM than in the fasted state (25 +/- 0.9%), concurrent with increased triglyceride formation from FFA. Insulin increased LC-CoA and ACSL activity associated with the PM. The changes in ACSL activity in response to insulin were associated with only minor changes in mass as determined by Western blotting.
  
  
  CONCLUSIONS
  It is hypothesized that ACSL plays an important role in targeting FFA to specific metabolic pathways or acylation sites in the cell, thus acting as an important control mechanism in fuel partitioning. Localization of ACSL at the PM may serve to decrease FFA efflux and trap FFA within the cell as LC-CoA.
authors.affiliation: Department of Medicine, Obesity Research Center, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Zang
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Yaney
authors.forename: Gino
authors.initials: G
authors.lastname: Vallega
authors.forename: Lisa
authors.initials: L
authors.lastname: Getty-Kaushik
authors.forename: Paul
authors.initials: P
authors.lastname: Pilch
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kandror
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Corkey
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D017667:Adipocytes / Q000201:enzymology / Q000648:ultrastructure; D000375:Aging; D000818:Animals; D002458:Cell Fractionation; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D003066:Coenzyme A Ligases / Q000032:analysis* / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000214:Acyl Coenzyme A; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids; D003066:Coenzyme A Ligases