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Pathway Description
Isobutyryl-CoA Dehydrogenase Deficiency
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-09-15
Isobutyryl-CoA dehydrogenase deficiency, also called IBDD, is an extremely rare inherited inborn error of metabolism (IEM) of valine metabolism. It is an autosomal recessive disorder that is caused by a defective isobutyryl-coenzyme A dehydrogenase. Approximately 30 people have been identified with this condition, although the frequency may be much higher since it is relatively asymptomatic. Isobutyryl-coenzyme A dehydrogenase is a mitochondrial protein that belongs to the acyl-CoA dehydrogenase family of enzymes. Its main function is to catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of branched-chain amino acids, specifically valine. This enzyme is responsible for the third step in the breakdown of valine and converts isobutyryl-CoA into methylacrylyl-CoA. Defects in the IBD enzyme function lead to elevated levels of valine in blood and other biofluids (valinemia). IBDD can be identified by elevated levels of C4-acylcarnitine via newborn screening. Most people with IBDD are asymptomatic. Some individuals with IBDD have developed features such as a weakened and enlarged heart (dilated cardiomyopathy), weak muscle tone (hypotonia), and developmental delay. This condition may also result in low numbers of red blood cells (anemia) and very low levels of carnitine in the blood, which is a compound that plays a role in converting certain foods into energy. Symptoms may be worsened by long periods of fasting or infections that increase the body's demand for energy. Treatment may include the use of L-carnitine supplements, frequent meals, and a low-valine diet.
References
Isobutyryl-CoA Dehydrogenase Deficiency References
Nguyen TV, Andresen BS, Corydon TJ, Ghisla S, Abd-El Razik N, Mohsen AW, Cederbaum SD, Roe DS, Roe CR, Lench NJ, Vockley J: Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans. Mol Genet Metab. 2002 Sep-Oct;77(1-2):68-79.
Pubmed: 12359132
Valine, Leucine, and Isoleucine Degradation References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y: The transcriptional landscape of the mammalian genome. Science. 2005 Sep 2;309(5740):1559-63. doi: 10.1126/science.1112014.
Pubmed: 16141072
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
Ballif BA, Carey GR, Sunyaev SR, Gygi SP: Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain. J Proteome Res. 2008 Jan;7(1):311-8. doi: 10.1021/pr0701254. Epub 2007 Nov 23.
Pubmed: 18034455
Fitzgerald J, Hutchison WM, Dahl HH: Isolation and characterisation of the mouse pyruvate dehydrogenase E1 alpha genes. Biochim Biophys Acta. 1992 May 7;1131(1):83-90. doi: 10.1016/0167-4781(92)90102-6.
Pubmed: 1581363
Tamura T, McMicken HW, Smith CV, Hansen TN: Gene structure for mouse glutathione reductase, including a putative mitochondrial targeting signal. Biochem Biophys Res Commun. 1997 Aug 18;237(2):419-22. doi: 10.1006/bbrc.1997.7153.
Pubmed: 9268726
Tutic M, Lu XA, Schirmer RH, Werner D: Cloning and sequencing of mammalian glutathione reductase cDNA. Eur J Biochem. 1990 Mar 30;188(3):523-8. doi: 10.1111/j.1432-1033.1990.tb15431.x.
Pubmed: 2185014
Wang S, Nadeau JH, Duncan A, Robert MF, Fontaine G, Schappert K, Johnson KR, Zietkiewicz E, Hruz P, Miziorko H, et al.: 3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL): cloning and characterization of a mouse liver HL cDNA and subchromosomal mapping of the human and mouse HL genes. Mamm Genome. 1993;4(7):382-7.
Pubmed: 8102917
Wang SP, Robert MF, Gibson KM, Wanders RJ, Mitchell GA: 3-Hydroxy-3-methylglutaryl CoA lyase (HL): mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients. Genomics. 1996 Apr 1;33(1):99-104. doi: 10.1006/geno.1996.0164.
Pubmed: 8617516
Schuldiner O, Eden A, Ben-Yosef T, Yanuka O, Simchen G, Benvenisty N: ECA39, a conserved gene regulated by c-Myc in mice, is involved in G1/S cell cycle regulation in yeast. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7143-8. doi: 10.1073/pnas.93.14.7143.
Pubmed: 8692959
Niwa O, Kumazaki T, Tsukiyama T, Soma G, Miyajima N, Yokoro K: A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line. Nucleic Acids Res. 1990 Nov 25;18(22):6709. doi: 10.1093/nar/18.22.6709.
Pubmed: 2251142
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 SMP0000523
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