Acyl-CoA synthetase isoforms 1, 4, and 5 are present in different subcellular membranes in rat liver and can be inhibited independently

The Journal of Biological Chemistry
T M LewinR A Coleman

Abstract

Inhibition studies have suggested that acyl-CoA synthetase (ACS, EC ) isoforms might regulate the use of acyl-CoAs by different metabolic pathways. In order to determine whether the subcellular locations differed for each of the three ACSs present in liver and whether these isoforms were regulated independently, non-cross-reacting peptide antibodies were raised against ACS1, ACS4, and ACS5. ACS1 was identified in endoplasmic reticulum, mitochondria-associated membrane (MAM), and cytosol, but not in mitochondria. ACS4 was present primarily in MAM, and the 76-kDa ACS5 protein was located in mitochondrial membrane. Consistent with these locations, N-ethylmaleimide, an inhibitor of ACS4, inhibited ACS activity 47% in MAM and 28% in endoplasmic reticulum. Troglitazone, a second ACS4 inhibitor, inhibited ACS activity <10% in microsomes and mitochondria and 45% in MAM. Triacsin C, a competitive inhibitor of both ACS1 and ACS4, inhibited ACS activity similarly in endoplasmic reticulum, MAM, and mitochondria, suggesting that a hitherto unidentified triacsin-sensitive ACS is present in mitochondria. ACS1, ACS4, and ACS5 were regulated independently by fasting and re-feeding. Fasting rats for 48 h resulted in a decrease in ACS4 protein, a...Continue Reading

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Citations

Apr 6, 2005·International Journal of Colorectal Disease·N ObermüllerN Gassler
Jun 6, 2003·Lipids·Hilde HeimliChristian A Drevon
Dec 4, 2003·Biochimica Et Biophysica Acta·Tal M Lewin, Rosalind A Coleman
Jun 28, 2005·Progress in Lipid Research·Jean E Vance, Rineke Steenbergen
Jan 30, 2002·Progress in Lipid Research·Simon Eaton
Jul 7, 2012·Chemical Research in Toxicology·Herve AloysiusRichard A Tschirret-Guth
Aug 2, 2012·Nature Reviews. Molecular Cell Biology·Rosario RizzutoCristina Mammucari
May 9, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Amber K Goetz, David J Dix
Mar 14, 2002·Current Opinion in Lipidology·Donald B Jump
Jul 11, 2002·Current Opinion in Clinical Nutrition and Metabolic Care·Hubert C Chen, Robert V Farese
May 9, 2006·Current Opinion in Lipidology·Douglas G Mashek, Rosalind A Coleman
May 12, 2011·American Journal of Physiology. Endocrinology and Metabolism·Katsuhiko Funai, Clay F Semenkovich
Aug 30, 2005·American Journal of Respiratory and Critical Care Medicine·Keith C DeRuisseauScott K Powers
Oct 6, 2009·Journal of Lipid Research·Gabriela Montero-MoranDawn L Brasaemle
Sep 10, 2011·Journal of Lipid Research·Mariana CookeFabiana Cornejo Maciel
Apr 19, 2008·Journal of Lipid Research·Judith StorchWilliam S Lagakos
Apr 1, 2008·Experimental Biology and Medicine·Eric Soupene, Frans A Kuypers
Dec 16, 2011·World Journal of Gastroenterology : WJG·Elke KaemmererNikolaus Gassler
Oct 25, 2011·International Journal of Medical Sciences·Julia KrammerRobert Ehehalt
Aug 1, 2007·Future Lipidology·Douglas G MashekRosalind A Coleman
May 14, 2014·Annual Review of Nutrition·Trisha J GrevengoedRosalind A Coleman
Feb 13, 2010·Annual Review of Physiology·Charles M Mansbach, Shadab A Siddiqi

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