{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:11:53Z","timestamp":1778616713083,"version":"3.51.4"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2013,8,15]],"date-time":"2013-08-15T00:00:00Z","timestamp":1376524800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003186","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T04:27:26Z","timestamp":1376627246000},"page":"e1003186","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":64,"title":["Biochemical Competition Makes Fatty-Acid \u03b2-Oxidation Vulnerable to Substrate Overload"],"prefix":"10.1371","volume":"9","author":[{"given":"Karen","family":"van Eunen","sequence":"first","affiliation":[]},{"given":"Sereh M. J.","family":"Simons","sequence":"additional","affiliation":[]},{"given":"Albert","family":"Gerding","sequence":"additional","affiliation":[]},{"given":"Aycha","family":"Bleeker","sequence":"additional","affiliation":[]},{"given":"Gijs","family":"den Besten","sequence":"additional","affiliation":[]},{"given":"Catharina M. L.","family":"Touw","sequence":"additional","affiliation":[]},{"given":"Sander M.","family":"Houten","sequence":"additional","affiliation":[]},{"given":"Bert K.","family":"Groen","sequence":"additional","affiliation":[]},{"given":"Klaas","family":"Krab","sequence":"additional","affiliation":[]},{"given":"Dirk-Jan","family":"Reijngoud","sequence":"additional","affiliation":[]},{"given":"Barbara M.","family":"Bakker","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2013,8,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.bbalip.2009.11.003","article-title":"Systems biology strategy to study lipotoxicity and the metabolic syndrome","volume":"1801","author":"M Oresic","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s10545-008-1005-8","article-title":"Metabolism as a complex genetic trait, a systems biology approach: Implications for inborn errors of metabolism and clinical diseases","volume":"31","author":"J Vockley","year":"2008","journal-title":"J Inherit Metab Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.ecl.2008.06.007","article-title":"Obesity and free fatty acids","volume":"37","author":"G Boden","year":"2008","journal-title":"Endocrinol Metab Clin North Am"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1007\/s00125-012-2554-9","article-title":"Inhibition of acetyl-CoA carboxylase 2 enhances skeletal muscle fatty acid oxidation and improves whole-body glucose homeostasis in db\/db mice","volume":"55","author":"S Glund","year":"2012","journal-title":"Diabetologia"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbalip.2009.09.014","article-title":"Role of fatty acid uptake and fatty acid beta-oxidation in mediating insulin resistance in heart and skeletal muscle","volume":"1801","author":"L Zhang","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cmet.2007.10.013","article-title":"Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance","volume":"7","author":"TR Koves","year":"2008","journal-title":"Cell Metab"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"22840","DOI":"10.1074\/jbc.M109.032888","article-title":"Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control","volume":"284","author":"RC Noland","year":"2009","journal-title":"J Biol Chem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1038\/oby.2009.510","article-title":"Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity","volume":"18","author":"SJ Mihalik","year":"2010","journal-title":"Obesity (Silver Spring)"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s10545-010-9188-1","article-title":"Current issues regarding treatment of mitochondrial fatty acid oxidation disorders","volume":"33","author":"U Spiekerkoetter","year":"2010","journal-title":"J Inherit Metab Dis"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s10545-010-9208-1","article-title":"Update on mitochondrial fatty acid oxidation disorders","volume":"33","author":"U Spiekerkoetter","year":"2010","journal-title":"J Inherit Metab Dis"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/BF02584214","article-title":"Computer simulation of metabolism in palmitate-perfused rat heart. I. palmitate oxidation","volume":"11","author":"MC Kohn","year":"1983","journal-title":"Ann Biomed Eng"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1752-0509-3-2","article-title":"Dynamic simulations on the mitochondrial fatty acid beta-oxidation network","volume":"3","author":"R Modre-Osprian","year":"2009","journal-title":"BMC Syst Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s11229-004-4421-9","article-title":"Emergence and its place in nature: A case study of biochemical networks","volume":"145","author":"FC Boogerd","year":"2005","journal-title":"Synthese"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1039\/c2mb25075f","article-title":"A compendium of inborn errors of metabolism mapped onto the human metabolic network","volume":"8","author":"S Sahoo","year":"2012","journal-title":"Mol Biosyst"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0021-9258(18)48390-1","article-title":"Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. I. purification and properties of very-long-chain acyl-coenzyme A dehydrogenase","volume":"267","author":"K Izai","year":"1992","journal-title":"The Journal of Biological Chemistry"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/S0021-9258(18)33160-0","article-title":"Separation and properties of five distinct acyl-CoA dehydrogenases from rat liver mitochondria. identification of a new 2-methyl branched chain acyl-CoA dehydrogenase","volume":"258","author":"Y Ikeda","year":"1983","journal-title":"J Biol Chem"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/S0021-9258(20)71245-7","article-title":"Purification and characterization of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases from rat liver mitochondria. isolation of the holo- and apoenzymes and conversion of the apoenzyme to the holoenzyme","volume":"260","author":"Y Ikeda","year":"1985","journal-title":"J Biol Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.bbalip.2009.05.006","article-title":"Mitochondrial long chain fatty acid beta-oxidation in man and mouse","volume":"1791","author":"M Chegary","year":"2009","journal-title":"Biochimica Et Biophysica Acta"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1042\/bst0280177","article-title":"The mitochondrial trifunctional protein: Centre of a beta-oxidation metabolon?","volume":"28","author":"S Eaton","year":"2000","journal-title":"Biochemical Society Transactions"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1042\/bj1320717","article-title":"The oxoacyl-coenzyme A thiolases of animal tissues","volume":"132","author":"B Middleton","year":"1973","journal-title":"Biochemical Journal"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1093\/oxfordjournals.jbchem.a133057","article-title":"Properties of mitochondria and peroxisomal enoyl-CoA hydratases from rat liver","volume":"88","author":"S Furuta","year":"1980","journal-title":"Journal of Biochemistry"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/oxfordjournals.jbchem.a133499","article-title":"Properties of peroxisomal 3-ketoacyl-coA thiolase from rat liver","volume":"90","author":"S Miyazawa","year":"1981","journal-title":"Journal of Biochemistry"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/S0021-9258(18)48391-3","article-title":"Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. II. purification and properties of enoyl-coenzyme A (CoA) hydratase\/3-hydroxyacyl-CoA dehydrogenase\/3-ketoacyl-CoA thiolase trifunctional protein","volume":"267","author":"Y Uchida","year":"1992","journal-title":"The Journal of Biological Chemistry"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/0003-9861(80)90189-7","article-title":"Purification and properties of mitochondrial and peroxisomal 3-hydroxyacyl-CoA dehydrogenase from rat liver","volume":"203","author":"T Osumi","year":"1980","journal-title":"Archives of Biochemistry and Biophysics"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/oxfordjournals.jbchem.a021307","article-title":"Two mitochondrial 3-hydroxyacyl-CoA dehydrogenases in bovine liver","volume":"119","author":"A Kobayashi","year":"1996","journal-title":"Journal of Biochemistry"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1063\/1.555939","article-title":"Thermodynamics of enzyme-catalyzed reactions: Part 1. oxidoreductases","volume":"22","author":"RN Goldberg","year":"1993","journal-title":"J Phys Chem Ref Data"},{"key":"ref27","first-page":"E95","article-title":"Lipid abnormalities in tissues of the KKAy mouse: Effects of pioglitazone on malonyl-CoA and diacylglycerol","volume":"267","author":"AK Saha","year":"1994","journal-title":"Am J Physiol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.2337\/db06-0062","article-title":"Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects","volume":"55","author":"GK Bandyopadhyay","year":"2006","journal-title":"Diabetes"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1096\/fasebj.13.14.2051","article-title":"Markers of capacity to utilize fatty acids in human skeletal muscle: Relation to insulin resistance and obesity and effects of weight loss","volume":"13","author":"JA Simoneau","year":"1999","journal-title":"FASEB J"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/jcp.21520","article-title":"Prolonged exposure to palmitate impairs fatty acid oxidation despite activation of AMP-activated protein kinase in skeletal muscle cells","volume":"217","author":"AS Pimenta","year":"2008","journal-title":"J Cell Physiol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1016\/j.bmc.2011.04.014","article-title":"Design of small molecule inhibitors of acetyl-CoA carboxylase 1 and 2 showing reduction of hepatic malonyl-CoA levels in vivo in obese zucker rats","volume":"19","author":"C Bengtsson","year":"2011","journal-title":"Bioorg Med Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/jcb.20944","article-title":"Expression of genes regulating malonyl-CoA in human skeletal muscle","volume":"99","author":"C Pender","year":"2006","journal-title":"J Cell Biochem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1038\/sj.emboj.7600298","article-title":"Structural basis for channelling mechanism of a fatty acid beta-oxidation multienzyme complex","volume":"23","author":"M Ishikawa","year":"2004","journal-title":"EMBO J"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"8748","DOI":"10.1016\/S0021-9258(17)47216-4","article-title":"Binding of the enzymes of fatty acid beta-oxidation and some related enzymes to pig heart inner mitochondrial membrane","volume":"259","author":"B Sumegi","year":"1984","journal-title":"J Biol Chem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1074\/jbc.270.2.530","article-title":"Evidence for intermediate channeling in mitochondrial beta-oxidation","volume":"270","author":"MA Nada","year":"1995","journal-title":"The Journal of Biological Chemistry"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1042\/bst0290279","article-title":"Impact of the intramitochondrial enzyme organization on fatty acid oxidation","volume":"29","author":"X Liang","year":"2001","journal-title":"Biochemical Society Transactions"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/S1388-1981(99)00027-X","article-title":"Intermediates of myocardial mitochondrial beta-oxidation: Possible channelling of NADH and of CoA esters","volume":"1437","author":"S Eaton","year":"1999","journal-title":"Biochimica Et Biophysica Acta"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"16483","DOI":"10.1016\/S0021-9258(19)84731-2","article-title":"Substrate channeling of NADH and binding of dehydrogenases to complex I","volume":"264","author":"T Fukushima","year":"1989","journal-title":"J Biol Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"15040","DOI":"10.1016\/S0021-9258(17)42511-7","article-title":"Complex I binds several mitochondrial NAD-coupled dehydrogenases","volume":"259","author":"B Sumegi","year":"1984","journal-title":"J Biol Chem"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0005-2760(91)90016-B","article-title":"Kinetic advantage of the interaction between the fatty acid beta-oxidation enzymes and the complexes of the respiratory chain","volume":"1081","author":"B Sumegi","year":"1991","journal-title":"Biochim Biophys Acta"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.2337\/db09-0580","article-title":"Metabolomics applied to diabetes research: Moving from information to knowledge","volume":"58","author":"JR Bain","year":"2009","journal-title":"Diabetes"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00394-011-0284-2","article-title":"Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: Evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency","volume":"51","author":"R Ringseis","year":"2012","journal-title":"Eur J Nutr"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1111\/j.1432-1033.2004.04213.x","article-title":"The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks","volume":"271","author":"HG Holzhutter","year":"2004","journal-title":"Eur J Biochem"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1113\/expphysiol.2009.049841","article-title":"Silencing of glycolysis in muscle: Experimental observation and numerical analysis","volume":"95","author":"JP Schmitz","year":"2010","journal-title":"Exp Physiol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1114\/1.1492813","article-title":"A computational model for glycogenolysis in skeletal muscle","volume":"30","author":"MJ Lambeth","year":"2002","journal-title":"Ann Biomed Eng"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"24525","DOI":"10.1074\/jbc.M701024200","article-title":"Computer modeling of mitochondrial tricarboxylic acid cycle, oxidative phosphorylation, metabolite transport, and electrophysiology","volume":"282","author":"F Wu","year":"2007","journal-title":"J Biol Chem"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/toxsci\/65.2.220","article-title":"Multiple effects of 2,2\u2032,5,5\u2032-tetrachlorobiphenyl on oxidative phosphorylation in rat liver mitochondria","volume":"65","author":"V Mildaziene","year":"2002","journal-title":"Toxicol Sci"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"Gnaiger E, Kuznetsov A, Schneeberger S, Seiler R, Brandacher G, <etal>et al<\/etal>.. (2000) Mitochondria in the cold. In: Heldmeier G, Klingenspor M, editors. Life in the Cold. Berlin Heidelberg New York: Springer. pp. 431.","DOI":"10.1007\/978-3-662-04162-8_45"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s10545-007-0492-3","article-title":"Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in the netherlands: The importance of enzyme analysis to ascertain true MCAD deficiency","volume":"31","author":"TG Derks","year":"2008","journal-title":"J Inherit Metab Dis"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1093\/clinchem\/24.10.1663","article-title":"Quantitative metabolic profiling based on gas chromatography","volume":"24","author":"SC Gates","year":"1978","journal-title":"Clin Chem"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003186","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T21:24:01Z","timestamp":1646342641000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003186"}},"subtitle":[],"editor":[{"given":"Jeffrey J.","family":"Saucerman","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2013,8,15]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2013,8,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003186","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,15]]}}}