The Biochemistry and Physiology of Mitochondrial Fatty Acid β-Oxidation and Its Genetic Disorders

Annual Review of Physiology - Tập 78 Số 1 - Trang 23-44 - 2016
Sander M. Houten1, Sara Violante2, Fátima V. Ventura3,4, Ronald J. A. Wanders5,5
1Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029;,
2Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; email: [email protected] , [email protected].
3Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, 1649-003 Lisboa, Portugal
4Metabolism and Genetics Group, Research Institute for Medicines and Pharmaceutical Sciences, iMed.ULisboa, 1649-003 Lisboa, Portugal;
5Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

Tóm tắt

Mitochondrial fatty acid β-oxidation (FAO) is the major pathway for the degradation of fatty acids and is essential for maintaining energy homeostasis in the human body. Fatty acids are a crucial energy source in the postabsorptive and fasted states when glucose supply is limiting. But even when glucose is abundantly available, FAO is a main energy source for the heart, skeletal muscle, and kidney. A series of enzymes, transporters, and other facilitating proteins are involved in FAO. Recessively inherited defects are known for most of the genes encoding these proteins. The clinical presentation of these disorders may include hypoketotic hypoglycemia, (cardio)myopathy, arrhythmia, and rhabdomyolysis and illustrates the importance of FAO during fasting and in hepatic and (cardio)muscular function. In this review, we present the current state of knowledge on the biochemistry and physiological functions of FAO and discuss the pathophysiological processes associated with FAO disorders.

Từ khóa


Tài liệu tham khảo

Knoop F, 1904, Beitr. Z. Chem. Phys. U. Pathol., 6, 150

10.1016/0163-7827(95)00011-9

10.1007/s10545-010-9061-2

10.1146/annurev.physiol.64.082201.154705

10.1172/JCI0215311

10.1203/01.PDR.0000083001.91588.BB

10.1152/physrev.00003.2009

10.1146/annurev-nutr-071813-105541

10.1042/bj3610417

10.1007/s00239-009-9263-0

10.1016/S1388-1981(00)00034-2

10.1016/S0005-2760(98)00053-8

10.1016/j.bbalip.2009.05.006

10.1093/hmg/10.19.2069

10.1073/pnas.95.26.15592

10.1074/jbc.273.10.5678

10.1172/JCI117947

10.1016/j.ymgme.2010.03.011

10.1074/jbc.M113.540260

10.1086/519219

10.1074/jbc.M504460200

10.1016/S0006-291X(02)02336-7

10.1093/hmg/ddt521

10.1093/hmg/ddv074

10.1093/brain/awq273

10.1038/ng.706

10.1016/j.cmet.2010.08.002

10.1016/j.braindev.2005.06.010

10.1371/journal.pcbi.1003186

10.1016/S1388-1981(00)00013-5

10.1016/0968-0004(87)90196-4

10.1074/jbc.M112228200

10.1111/febs.13179

10.1096/fj.12-206326

10.1056/NEJM197003052821026

10.1146/annurev.nutr.26.061505.111258

10.1152/physrev.00015.2009

10.1016/S1050-1738(00)00077-3

10.1152/physrev.00023.2004

10.1113/jphysiol.2007.128348

10.2337/db12-0466

10.1152/physrev.1986.66.2.469

10.1038/nm.3762

10.1056/NEJMoa1307581

10.1128/MCB.15.6.3012

10.1172/JCI6223

10.1073/pnas.96.13.7473

10.1194/jlr.M024463

Rodriguez JC, 1994, J. Biol. Chem., 269, 18767, 10.1016/S0021-9258(17)32234-2

10.1172/JCI3949

10.1152/physrev.00027.2013

10.1074/jbc.M203997200

10.2337/diabetes.51.4.901

10.1074/jbc.M206324200

10.1172/JCI108764

10.1042/bj3170791

10.1042/BJ20121110

10.1038/nature07813

10.1074/jbc.M113.510354

10.1038/nature08778

10.1093/hmg/ddu059

10.1126/scisignal.2003252

10.1074/jbc.M114.635102

10.1203/01.PDR.0000103931.80055.06

10.1007/978-3-642-40337-8_44

10.1203/00006450-199711000-00002

10.1172/JCI114624

10.1093/hmg/ddu218

10.1016/S0022-3476(94)70363-9

10.1016/j.ymgme.2004.12.010

10.1016/S0140-6736(07)60029-4

10.1016/S0009-8981(97)00185-X

10.1023/A:1005556207210

10.1007/s10545-012-9542-6

10.1007/s10545-013-9628-9

10.1542/peds.109.1.99

10.1067/mpd.2003.231

10.1111/cge.12112

10.1111/j.1651-2227.2003.tb00586.x

10.1016/j.jpeds.2005.12.028

10.1161/01.CIR.100.22.2248

10.1542/peds.2013-1105

10.1016/j.nmd.2009.02.007

10.1016/j.nmd.2010.06.018

10.1016/j.ymgme.2009.07.011

10.1002/mus.21157

Diekman EF, 2014, J. Inherit. Metab. Dis., 37, 405, 10.1007/s10545-013-9666-3

10.1136/jnnp.58.2.209

10.1007/s10545-010-9115-5

10.1016/j.ymgme.2012.02.015

10.1203/01.PDR.0000161413.42874.74

Tyni T, 2002, Pediatr. Res., 52, 595

10.2337/diabetes.53.1.221

10.1074/jbc.M110.123638

10.1093/brain/awu216

10.1002/humu.22730

10.1373/clinchem.2003.022178

10.1016/j.bbadis.2013.02.012

10.1096/fj.12-216689

10.1016/j.bbadis.2010.06.002

10.1016/0005-2736(94)90281-X

10.1007/s10545-010-9104-8

10.1016/S0009-8981(98)00188-0

10.1007/BF01799333

105. Diekman EF, Ferdinandusse S, van der Pol L, Waterham HR, Ruiter JP, et al. 2015. Fatty acid oxidation flux predicts the clinical severity of VLCAD deficiency.Genet. Med.In press

10.1161/01.RES.0000088786.19197.E4

10.1152/ajpheart.00811.2005

10.1194/jlr.M800221-JLR200

10.1093/cvr/cvm005

10.1093/cvr/cvt212

10.1161/CIRCIMAGING.111.963751

10.1038/labinvest.2009.86

10.1093/hmg/ddt382

10.1007/BF00563017

10.1203/00006450-198901000-00010

10.1258/002367788780746511

10.1016/0006-291X(91)91532-H

10.1038/5030

10.1016/j.ymgme.2007.10.006

10.1016/j.ymgme.2005.07.021

10.1172/JCI12590

10.1210/en.2011-1547

10.1074/jbc.M110993200

10.1371/journal.pgen.1000543

10.1371/journal.pgen.0010023

10.1152/ajpheart.00931.2012

10.1002/ana.20168

10.1002/ana.20320

10.1002/hep.22101

10.2337/diab.17.4.194

Scrutton MC, 1967, J. Biol. Chem., 242, 1723, 10.1016/S0021-9258(18)96061-8

10.1203/PDR.0b013e31816ff6f0

10.1007/s10863-012-9481-9

10.1016/j.ymgme.2005.07.030

10.1016/j.bbrc.2006.11.109

10.1007/s10545-013-9604-4

10.1016/j.bbadis.2014.02.001

10.1152/ajpheart.01275.2010

10.1096/fj.14-250241

10.1007/s10545-010-9188-1

10.1172/JCI113978

10.1007/s10545-010-9105-7

10.1016/j.ymgme.2006.06.004

10.1016/j.ymgme.2011.09.030

10.1212/01.wnl.0000318283.42961.e9

10.1093/hmg/ddi303

10.1056/NEJMc0806334

10.1038/clpt.2010.55

10.1212/WNL.0000000000000118

10.1038/nm.3545