Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
2-Aminoadipic 2-Oxoadipic Aciduria
Homo sapiens
Disease Pathway
Created: 2014-06-23
Last Updated: 2022-11-24
2-Aminoadipic 2-oxoadipic aciduria is a disorder of lysine metabolism caused by a defective DHTKD1 gene. DHTKD1 is predicted to code for a component of a supercomplex similar to the 2-oxoglutarate dehydrogenase complex (OGDHc) which catalyzes the conversion of 2-oxoadipate into glutaryl-CoA. This disease is characterized by a large accumulation of 2-oxoadipate and 2-hydroxyadipate in the urine. Symptoms of the disease include mild to severe intellectual disability, developmental delay, ataxia, muscular hypotonia, and epilepsy. However, most cases are asymptomatic.
References
2-Aminoadipic 2-Oxoadipic Aciduria References
Danhauser K, Sauer SW, Haack TB, Wieland T, Staufner C, Graf E, Zschocke J, Strom TM, Traub T, Okun JG, Meitinger T, Hoffmann GF, Prokisch H, Kolker S: DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria. Am J Hum Genet. 2012 Dec 7;91(6):1082-7. doi: 10.1016/j.ajhg.2012.10.006. Epub 2012 Nov 8.
Pubmed: 23141293
Biagosch C, Ediga RD, Hensler SV, Faerberboeck M, Kuehn R, Wurst W, Meitinger T, Kolker S, Sauer S, Prokisch H: Elevated glutaric acid levels in Dhtkd1-/Gcdh- double knockout mice challenge our current understanding of lysine metabolism. Biochim Biophys Acta Mol Basis Dis. 2017 Sep;1863(9):2220-2228. doi: 10.1016/j.bbadis.2017.05.018. Epub 2017 May 22.
Pubmed: 28545977
Lysine 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.
Sacksteder KA, Biery BJ, Morrell JC, Goodman BK, Geisbrecht BV, Cox RP, Gould SJ, Geraghty MT: Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia. Am J Hum Genet. 2000 Jun;66(6):1736-43. doi: 10.1086/302919. Epub 2000 Apr 20.
Pubmed: 10775527
Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. doi: 10.1038/nature01782.
Pubmed: 12853948
Dancis J, Hutzler J, Cox RP: Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology. Am J Hum Genet. 1979 May;31(3):290-9.
Pubmed: 463877
Brocker C, Lassen N, Estey T, Pappa A, Cantore M, Orlova VV, Chavakis T, Kavanagh KL, Oppermann U, Vasiliou V: Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. J Biol Chem. 2010 Jun 11;285(24):18452-63. doi: 10.1074/jbc.M109.077925. Epub 2010 Mar 5.
Pubmed: 20207735
Plecko B, Paul K, Paschke E, Stoeckler-Ipsiroglu S, Struys E, Jakobs C, Hartmann H, Luecke T, di Capua M, Korenke C, Hikel C, Reutershahn E, Freilinger M, Baumeister F, Bosch F, Erwa W: Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene. Hum Mutat. 2007 Jan;28(1):19-26. doi: 10.1002/humu.20433.
Pubmed: 17068770
Lee P, Kuhl W, Gelbart T, Kamimura T, West C, Beutler E: Homology between a human protein and a protein of the green garden pea. Genomics. 1994 May 15;21(2):371-8. doi: 10.1006/geno.1994.1279.
Pubmed: 8088832
Goh DL, Patel A, Thomas GH, Salomons GS, Schor DS, Jakobs C, Geraghty MT: Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). Mol Genet Metab. 2002 Jul;76(3):172-80.
Pubmed: 12126930
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
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
Janssen U, Davis EM, Le Beau MM, Stoffel W: Human mitochondrial enoyl-CoA hydratase gene (ECHS1): structural organization and assignment to chromosome 10q26.2-q26.3. Genomics. 1997 Mar 15;40(3):470-5. doi: 10.1006/geno.1996.4597.
Pubmed: 9073515
Peters H, Buck N, Wanders R, Ruiter J, Waterham H, Koster J, Yaplito-Lee J, Ferdinandusse S, Pitt J: ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism. Brain. 2014 Nov;137(Pt 11):2903-8. doi: 10.1093/brain/awu216. Epub 2014 Aug 14.
Pubmed: 25125611
Haack TB, Jackson CB, Murayama K, Kremer LS, Schaller A, Kotzaeridou U, de Vries MC, Schottmann G, Santra S, Buchner B, Wieland T, Graf E, Freisinger P, Eggimann S, Ohtake A, Okazaki Y, Kohda M, Kishita Y, Tokuzawa Y, Sauer S, Memari Y, Kolb-Kokocinski A, Durbin R, Hasselmann O, Cremer K, Albrecht B, Wieczorek D, Engels H, Hahn D, Zink AM, Alston CL, Taylor RW, Rodenburg RJ, Trollmann R, Sperl W, Strom TM, Hoffmann GF, Mayr JA, Meitinger T, Bolognini R, Schuelke M, Nuoffer JM, Kolker S, Prokisch H, Klopstock T: Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement. Ann Clin Transl Neurol. 2015 May;2(5):492-509. doi: 10.1002/acn3.189. Epub 2015 Mar 13.
Pubmed: 26000322
Vredendaal PJ, van den Berg IE, Malingre HE, Stroobants AK, Olde Weghuis DE, Berger R: Human short-chain L-3-hydroxyacyl-CoA dehydrogenase: cloning and characterization of the coding sequence. Biochem Biophys Res Commun. 1996 Jun 25;223(3):718-23. doi: 10.1006/bbrc.1996.0961.
Pubmed: 8687463
Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. doi: 10.1038/nature03466.
Pubmed: 15815621
Fukao T, Yamaguchi S, Kano M, Orii T, Fujiki Y, Osumi T, Hashimoto T: Molecular cloning and sequence of the complementary DNA encoding human mitochondrial acetoacetyl-coenzyme A thiolase and study of the variant enzymes in cultured fibroblasts from patients with 3-ketothiolase deficiency. J Clin Invest. 1990 Dec;86(6):2086-92. doi: 10.1172/JCI114946.
Pubmed: 1979337
Kano M, Fukao T, Yamaguchi S, Orii T, Osumi T, Hashimoto T: Structure and expression of the human mitochondrial acetoacetyl-CoA thiolase-encoding gene. Gene. 1991 Dec 30;109(2):285-90. doi: 10.1016/0378-1119(91)90623-j.
Pubmed: 1684944
Hoshide R, Ikeda Y, Karashima S, Matsuura T, Komaki S, Kishino T, Niikawa N, Endo F, Matsuda I: Molecular cloning, tissue distribution, and chromosomal localization of human cationic amino acid transporter 2 (HCAT2). Genomics. 1996 Dec 1;38(2):174-8. doi: 10.1006/geno.1996.0613.
Pubmed: 8954799
Closs EI, Graf P, Habermeier A, Cunningham JM, Forstermann U: Human cationic amino acid transporters hCAT-1, hCAT-2A, and hCAT-2B: three related carriers with distinct transport properties. Biochemistry. 1997 May 27;36(21):6462-8. doi: 10.1021/bi962829p.
Pubmed: 9174363
Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. doi: 10.1038/nature04406.
Pubmed: 16421571
Wu Q, Zhang T, Cheng JF, Kim Y, Grimwood J, Schmutz J, Dickson M, Noonan JP, Zhang MQ, Myers RM, Maniatis T: Comparative DNA sequence analysis of mouse and human protocadherin gene clusters. Genome Res. 2001 Mar;11(3):389-404. doi: 10.1101/gr.167301.
Pubmed: 11230163
Camacho JA, Rioseco-Camacho N, Andrade D, Porter J, Kong J: Cloning and characterization of human ORNT2: a second mitochondrial ornithine transporter that can rescue a defective ORNT1 in patients with the hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a urea cycle disorder. Mol Genet Metab. 2003 Aug;79(4):257-71.
Pubmed: 12948741
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