
Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Fatty Acid Elongation in Mitochondria
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-08-16
Cells typically contain large amounts of C18 and C20 fatty acids. Longer chain fatty acids are found in certain specialized tissues (myelin contains high amounts of C22 and C24 components). Even longer chain fatty acids are derived from either dietary sources or from elongation of C16-CoA or C18-CoA formed by the cytoplasmic fatty acid synthetase system. All of the fatty acids needed by the body can be synthesized from palmitate (C16:0) except the essential, polyunsaturated fatty acids such as linoleate and linolenate. To create longer, shorter, oxidized, reduced fatty acids, palmitic acid is subjected to enzymatic reactions by reductases, hydroxylases, elongases and mixed function oxidases. There are 3 major processes that modify palmitic acid: elongation, desaturation and hydroxylation. Elongation of fatty acids may occur at endoplasmic reticulum where fatty acid molecules of length up to C24 may be produced. Mitochondrial elongation may result in fatty acids up to C16 in length. Fatty acid elongation in mitochondria is essentially the reverse of beta-oxidation for fatty acid oxidation. In particular, both pathways make use of acetyl-CoA acyltransferase, 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase. The final step of fatty acid elongation uses enoyl-CoA reductase (not part of the beta-oxidation pathway). The elongation takes place in the mitochondrial matrix. In liver and kidney fatty acid elongation operates best in the presence of both NADH and NADPH, whereas in heart and skeletal muscle, only NADH is required. The mitochondrial pathway is important for elongating fatty acids containing 14 or fewer carbon atoms. Short chain fatty acids (SCFA) are fatty acids with aliphatic tails of less than six carbons. Medium chain fatty acids (MCFA) are fatty acids with aliphatic tails of 612 carbons. Long chain fatty acids (LCFA) are fatty acids with aliphatic tails longer than 12 carbons. Very Long chain fatty acids (VLCFA) are fatty acids with aliphatic tails longer than 22 carbons.
References
Fatty Acid Elongation in Mitochondria References
Powell AJ, Read JA, Banfield MJ, Gunn-Moore F, Yan SD, Lustbader J, Stern AR, Stern DM, Brady RL: Recognition of structurally diverse substrates by type II 3-hydroxyacyl-CoA dehydrogenase (HADH II)/amyloid-beta binding alcohol dehydrogenase (ABAD). J Mol Biol. 2000 Oct 20;303(2):311-27. doi: 10.1006/jmbi.2000.4139.
Pubmed: 11023795
Kamijo T, Aoyama T, Miyazaki J, Hashimoto T: Molecular cloning of the cDNAs for the subunits of rat mitochondrial fatty acid beta-oxidation multienzyme complex. Structural and functional relationships to other mitochondrial and peroxisomal beta-oxidation enzymes. J Biol Chem. 1993 Dec 15;268(35):26452-60.
Pubmed: 8253773
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Uchida Y, Izai K, Orii T, Hashimoto T: 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. J Biol Chem. 1992 Jan 15;267(2):1034-41.
Pubmed: 1730633
Minami-Ishii N, Taketani S, Osumi T, Hashimoto T: Molecular cloning and sequence analysis of the cDNA for rat mitochondrial enoyl-CoA hydratase. Structural and evolutionary relationships linked to the bifunctional enzyme of the peroxisomal beta-oxidation system. Eur J Biochem. 1989 Oct 20;185(1):73-8. doi: 10.1111/j.1432-1033.1989.tb15083.x.
Pubmed: 2806264
Muller-Newen G, Janssen U, Stoffel W: Enoyl-CoA hydratase and isomerase form a superfamily with a common active-site glutamate residue. Eur J Biochem. 1995 Feb 15;228(1):68-73. doi: 10.1111/j.1432-1033.1995.tb20230.x.
Pubmed: 7883013
Masuda N, Yasumo H, Furusawa T, Tsukamoto T, Sadano H, Osumi T: Nuclear receptor binding factor-1 (NRBF-1), a protein interacting with a wide spectrum of nuclear hormone receptors. Gene. 1998 Oct 23;221(2):225-33. doi: 10.1016/s0378-1119(98)00461-2.
Pubmed: 9795230
Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F: Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493-521. doi: 10.1038/nature02426.
Pubmed: 15057822
Kim DG, Yoo JC, Kim E, Lee YS, Yarishkin OV, Lee DY, Lee KH, Hong SG, Hwang EM, Park JY: A Novel Cytosolic Isoform of Mitochondrial Trans-2-Enoyl-CoA Reductase Enhances Peroxisome Proliferator-Activated Receptor alpha Activity. Endocrinol Metab (Seoul). 2014 Jun;29(2):185-94. doi: 10.3803/EnM.2014.29.2.185. Epub 2014 Jun 26.
Pubmed: 25031892
Arakawa H, Takiguchi M, Amaya Y, Nagata S, Hayashi H, Mori M: cDNA-derived amino acid sequence of rat mitochondrial 3-oxoacyl-CoA thiolase with no transient presequence: structural relationship with peroxisomal isozyme. EMBO J. 1987 May;6(5):1361-6.
Pubmed: 3038520
Yamashita H, Itsuki A, Kimoto M, Hiemori M, Tsuji H: Acetate generation in rat liver mitochondria; acetyl-CoA hydrolase activity is demonstrated by 3-ketoacyl-CoA thiolase. Biochim Biophys Acta. 2006 Jan;1761(1):17-23. doi: 10.1016/j.bbalip.2006.01.001. Epub 2006 Jan 30.
Pubmed: 16476568
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000054
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings