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Pathway Description
Long Chain Acyl-CoA Dehydrogenase Deficiency (LCAD)
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-08-16
Very Long Chain Acyl CoA Dehydrogenase Deficiency (VLCADD) is a rare disorder that is inherited through an autosomal recessive trait, and prevents the body from properly metabolizing very long chain fatty acids. This disorder occurs in the mitochondria, where the metabolization of fatty acids takes place. Early-onset VLCADD patients usually begin to exhibit symptoms just days or weeks after birth. Hypoglycemia, lethargy and irritability are symptoms associated with this disorder. Patients will also be at risk for hypertrophic cardiomyopathy and other heart conditions from age two months to two years. It can be diagnosed through a research of family history and generally a urine analysis will reveal that the patient has reduced of absent ketone bodies. To help control acute episodes, treatment includes maintaining a high carbohydrate and low fat diet, and avoiding fasting for more than 12 hours.
References
Long Chain Acyl-CoA Dehydrogenase Deficiency (LCAD) References
Goetzman ES, Alcorn JF, Bharathi SS, Uppala R, McHugh KJ, Kosmider B, Chen R, Zuo YY, Beck ME, McKinney RW, Skilling H, Suhrie KR, Karunanidhi A, Yeasted R, Otsubo C, Ellis B, Tyurina YY, Kagan VE, Mallampalli RK, Vockley J: Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactant dysfunction. J Biol Chem. 2014 Apr 11;289(15):10668-79. doi: 10.1074/jbc.M113.540260. Epub 2014 Mar 3.
Pubmed: 24591516
Zhang D, Liu ZX, Choi CS, Tian L, Kibbey R, Dong J, Cline GW, Wood PA, Shulman GI: Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17075-80. doi: 10.1073/pnas.0707060104. Epub 2007 Oct 16.
Pubmed: 17940018
Fatty Acid Metabolism References
Woeltje KF, Esser V, Weis BC, Sen A, Cox WF, McPhaul MJ, Slaughter CA, Foster DW, McGarry JD: Cloning, sequencing, and expression of a cDNA encoding rat liver mitochondrial carnitine palmitoyltransferase II. J Biol Chem. 1990 Jun 25;265(18):10720-5.
Pubmed: 2355018
de Vries Y, Arvidson DN, Waterham HR, Cregg JM, Woldegiorgis G: Functional characterization of mitochondrial carnitine palmitoyltransferases I and II expressed in the yeast Pichia pastoris. Biochemistry. 1997 Apr 29;36(17):5285-92. doi: 10.1021/bi962875p.
Pubmed: 9136891
Brown NF, Esser V, Gonzalez AD, Evans CT, Slaughter CA, Foster DW, McGarry JD: Mitochondrial import and processing of rat liver carnitine palmitoyltransferase II defines the amino terminus of the mature protein. Possibility of differential modification of the rat and human isoforms. J Biol Chem. 1991 Aug 15;266(23):15446-9.
Pubmed: 1869564
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
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
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
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
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
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
Esser V, Britton CH, Weis BC, Foster DW, McGarry JD: Cloning, sequencing, and expression of a cDNA encoding rat liver carnitine palmitoyltransferase I. Direct evidence that a single polypeptide is involved in inhibitor interaction and catalytic function. J Biol Chem. 1993 Mar 15;268(8):5817-22.
Pubmed: 8449948
Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, Hashimoto T, Yamamoto T: Structure and regulation of rat long-chain acyl-CoA synthetase. J Biol Chem. 1990 May 25;265(15):8681-5.
Pubmed: 2341402
Distler AM, Kerner J, Hoppel CL: Post-translational modifications of rat liver mitochondrial outer membrane proteins identified by mass spectrometry. Biochim Biophys Acta. 2007 May;1774(5):628-36. doi: 10.1016/j.bbapap.2007.03.012. Epub 2007 Mar 28.
Pubmed: 17478130
Iijima H, Fujino T, Minekura H, Suzuki H, Kang MJ, Yamamoto T: Biochemical studies of two rat acyl-CoA synthetases, ACS1 and ACS2. Eur J Biochem. 1996 Dec 1;242(2):186-90. doi: 10.1111/j.1432-1033.1996.0186r.x.
Pubmed: 8973631
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 SMP0000539
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