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Pathway Description
Acylcarnitine (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoylcarnitine
Homo sapiens
Metabolic Pathway
Created: 2021-04-17
Last Updated: 2021-04-21
(5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoylcarnitine is an acylcarnitine. The general role of acylcarnitines is to transport acyl-groups, organic acids and fatty acids, from the cytoplasm into the mitochondria so that they can be broken down to produce energy. As part of this process, (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoic acid is first transported into the cell via the long-chain fatty acid transport protein 1 (FATP1). Once inside the cell it undergoes a reaction to form an acyl-CoA derivative called (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoyl-CoA. This reaction is facilitated by the long-chain fatty-acid CoA ligase 1 protein, which adds a CoA moiety to appropriate acyl groups. Many acyl-CoA groups will then further react with other zwitterionic compounds such as carnitine (to form acylcarnitines) and amino acids (to form acyl amides). The carnitine needed to form acylcarnitines inside the cell is transported into the cell by the organic cation/carnitine transporter 2. In forming an acylcarnitine derivative, (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoyl-CoA reacts with L-carnitine to form (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoylcarnitine. This reaction is catalyzed by carnitine O-palmitoyltransferase. This enzyme resides in the mitochondrial outer membrane. While this reaction takes place, the (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoylcarnitine is moved into the mitochondrial intermembrane space. Following the reaction, the newly synthesized acylcarnitine is transported into the mitochondrial matrix by a mitochondrial carnitine/acylcarnitine carrier protein found in the mitochondrial inner membrane. Once in the matrix, (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoylcarnitine can react with the carnitine O-palmitoyltransferase 2 enzyme found in the mitochondrial inner membrane to once again form (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoyl-CoA and L-carnitine. (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoyl-CoA then enters into the mitochondrial beta-oxidation pathway to form aceytl-CoA. Acetyl-CoA can go on to enter the TCA cycle, or it can react with L-carnitine to form L-acetylcarnitine in a reaction catalyzed by Carnitine O-acetyltransferase. This reaction can occur in both directions, and L-acetylcarnitine and CoA can react to form acetyl-CoA and L-carnitine in certain circumstances. Finally, acetyl-CoA in the cytosol can be catalyzed by acetyl-CoA carboxylase 1 to form malonyl-CoA, which inhibits the action of carnitine O-palmitoyltransferase 1, thereby preventing (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoylcarnitine from forming and thereby preventing it from being transported into the mitochondria.
References
Acylcarnitine (5Z,7S,8E,10Z,13Z,15E,17S,19Z)-7,17-dihydroxydocosa-5,8,10,13,15,19-hexaenoylcarnitine References
Abe T, Fujino T, Fukuyama R, Minoshima S, Shimizu N, Toh H, Suzuki H, Yamamoto T: Human long-chain acyl-CoA synthetase: structure and chromosomal location. J Biochem. 1992 Jan;111(1):123-8. doi: 10.1093/oxfordjournals.jbchem.a123707.
Pubmed: 1607358
Ghosh B, Barbosa E, Singh I: Molecular cloning and sequencing of human palmitoyl-CoA ligase and its tissue specific expression. Mol Cell Biochem. 1995 Oct 4;151(1):77-81. doi: 10.1007/bf01076899.
Pubmed: 8584017
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Gobin S, Bonnefont JP, Prip-Buus C, Mugnier C, Ferrec M, Demaugre F, Saudubray JM, Rostane H, Djouadi F, Wilcox W, Cederbaum S, Haas R, Nyhan WL, Green A, Gray G, Girard J, Thuillier L: Organization of the human liver carnitine palmitoyltransferase 1 gene ( CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia. Hum Genet. 2002 Aug;111(2):179-89. doi: 10.1007/s00439-002-0752-0. Epub 2002 Jul 16.
Pubmed: 12189492
Britton CH, Schultz RA, Zhang B, Esser V, Foster DW, McGarry JD: Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1984-8. doi: 10.1073/pnas.92.6.1984.
Pubmed: 7892212
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
Abu-Elheiga L, Jayakumar A, Baldini A, Chirala SS, Wakil SJ: Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4011-5. doi: 10.1073/pnas.92.9.4011.
Pubmed: 7732023
Mao J, Chirala SS, Wakil SJ: Human acetyl-CoA carboxylase 1 gene: presence of three promoters and heterogeneity at the 5'-untranslated mRNA region. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7515-20. doi: 10.1073/pnas.1332670100. Epub 2003 Jun 16.
Pubmed: 12810950
Sinilnikova OM, Ginolhac SM, Magnard C, Leone M, Anczukow O, Hughes D, Moreau K, Thompson D, Coutanson C, Hall J, Romestaing P, Gerard JP, Bonadona V, Lasset C, Goldgar DE, Joulin V, Venezia ND, Lenoir GM: Acetyl-CoA carboxylase alpha gene and breast cancer susceptibility. Carcinogenesis. 2004 Dec;25(12):2417-24. doi: 10.1093/carcin/bgh273. Epub 2004 Aug 27.
Pubmed: 15333468
FitzPatrick DR, Hill A, Tolmie JL, Thorburn DR, Christodoulou J: The molecular basis of malonyl-CoA decarboxylase deficiency. Am J Hum Genet. 1999 Aug;65(2):318-26. doi: 10.1086/302492.
Pubmed: 10417274
Sacksteder KA, Morrell JC, Wanders RJ, Matalon R, Gould SJ: MCD encodes peroxisomal and cytoplasmic forms of malonyl-CoA decarboxylase and is mutated in malonyl-CoA decarboxylase deficiency. J Biol Chem. 1999 Aug 27;274(35):24461-8. doi: 10.1074/jbc.274.35.24461.
Pubmed: 10455107
Gao J, Waber L, Bennett MJ, Gibson KM, Cohen JC: Cloning and mutational analysis of human malonyl-coenzyme A decarboxylase. J Lipid Res. 1999 Jan;40(1):178-82.
Pubmed: 9869665
Wataya K, Akanuma J, Cavadini P, Aoki Y, Kure S, Invernizzi F, Yoshida I, Kira J, Taroni F, Matsubara Y, Narisawa K: Two CPT2 mutations in three Japanese patients with carnitine palmitoyltransferase II deficiency: functional analysis and association with polymorphic haplotypes and two clinical phenotypes. Hum Mutat. 1998;11(5):377-86. doi: 10.1002/(SICI)1098-1004(1998)11:5<377::AID-HUMU5>3.0.CO;2-E.
Pubmed: 9600456
Finocchiaro G, Taroni F, Rocchi M, Martin AL, Colombo I, Tarelli GT, DiDonato S: cDNA cloning, sequence analysis, and chromosomal localization of the gene for human carnitine palmitoyltransferase. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):661-5. doi: 10.1073/pnas.88.2.661.
Pubmed: 1988962
Finocchiaro G, Taroni F, Rocchi M, Liras Martin A, Colombo I, Tarelli GT, DiDonato S: cDNA cloning, sequence analysis, and chromosomal localization of human carnitine palmitoyltransferase. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10981. doi: 10.1073/pnas.88.23.10981.
Pubmed: 1961767
Huizing M, Iacobazzi V, Ijlst L, Savelkoul P, Ruitenbeek W, van den Heuvel L, Indiveri C, Smeitink J, Trijbels F, Wanders R, Palmieri F: Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient. Am J Hum Genet. 1997 Dec;61(6):1239-45. doi: 10.1086/301628.
Pubmed: 9399886
Iacobazzi V, Naglieri MA, Stanley CA, Wanders RJ, Palmieri F: The structure and organization of the human carnitine/acylcarnitine translocase (CACT1) gene2. Biochem Biophys Res Commun. 1998 Nov 27;252(3):770-4. doi: 10.1006/bbrc.1998.9738.
Pubmed: 9837782
Wu X, Prasad PD, Leibach FH, Ganapathy V: cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95. doi: 10.1006/bbrc.1998.8669.
Pubmed: 9618255
Tamai I, Ohashi R, Nezu J, Yabuuchi H, Oku A, Shimane M, Sai Y, Tsuji A: Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem. 1998 Aug 7;273(32):20378-82. doi: 10.1074/jbc.273.32.20378.
Pubmed: 9685390
Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N, Nikaido H, Sai Y, Koizumi A, Shoji Y, Takada G, Matsuishi T, Yoshino M, Kato H, Ohura T, Tsujimoto G, Hayakawa J, Shimane M, Tsuji A: Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet. 1999 Jan;21(1):91-4. doi: 10.1038/5030.
Pubmed: 9916797
Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. doi: 10.1038/nature02465.
Pubmed: 15164053
Corti O, DiDonato S, Finocchiaro G: Divergent sequences in the 5' region of cDNA suggest alternative splicing as a mechanism for the generation of carnitine acetyltransferases with different subcellular localizations. Biochem J. 1994 Oct 1;303 ( Pt 1):37-41. doi: 10.1042/bj3030037.
Pubmed: 7945262
This pathway was generated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
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