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Pathway Description
Succinyl CoA: 3-Ketoacid CoA Transferase Deficiency
Homo sapiens
Disease Pathway
Created: 2022-12-14
Last Updated: 2023-10-25
Disease Pathway
Succinyl CoA: 3-Ketoacid CoA Transferase (SCOT) deficiency is a rare inherited metabolic disorder causing reduction of ketone body utilization. In normal functioning patients, ketone bodies such as Acetoacetate (AcAc) and 3‐hydroxybutyrate (3HB) are metabolized inside the liver from free fatty acids. Next, ketone bodies are transported to extrahepatic tissues via the blood stream. Once in extrahepatic tissues, SCOT converts AcAc to acetoacetyl‐CoA and T2 cleaves acetoacetyl‐CoA into acetyl‐CoA. This process is crucial for producing alternative energy sources to glucose in order to maintain blood glucose levels. Patients with SCOT deficiency have this process disturbed and ketoacidosis which is the acidification of the bloodstream due to excess ketone body accumulation, can occur. Current treatments include avoiding actions that could onset ketoacidosis such as fasting and early infusion of glucose. The severity of SCOT deficiency differs from patient to patient. Some exhibit severe genotypes where ketones are always in abundance in the body, while others could have mild genotypes with no preeminent ketosis however both could exhibit ketoacidotic episodes.
References
Succinyl CoA: 3-Ketoacid CoA Transferase Deficiency References
Snyderman SE, Sansaricq C, Middleton B: Succinyl-CoA:3-ketoacid CoA-transferase deficiency. Pediatrics. 1998 Apr;101(4 Pt 1):709-11. doi: 10.1542/peds.101.4.709.
Pubmed: 9521962
Hori T, Yamaguchi S, Shinkaku H, Horikawa R, Shigematsu Y, Takayanagi M, Fukao T: Inborn errors of ketone body utilization. Pediatr Int. 2015;57(1):41-8. doi: 10.1111/ped.12585.
Pubmed: 25559898
Sasai H, Aoyama Y, Otsuka H, Abdelkreem E, Naiki Y, Kubota M, Sekine Y, Itoh M, Nakama M, Ohnishi H, Fujiki R, Ohara O, Fukao T: Heterozygous carriers of succinyl-CoA:3-oxoacid CoA transferase deficiency can develop severe ketoacidosis. J Inherit Metab Dis. 2017 Nov;40(6):845-852. doi: 10.1007/s10545-017-0065-z. Epub 2017 Jul 10.
Pubmed: 28695376
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.
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
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
Camarero N, Mascaro C, Mayordomo C, Vilardell F, Haro D, Marrero PF: Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer. Mol Cancer Res. 2006 Sep;4(9):645-53. doi: 10.1158/1541-7786.MCR-05-0267. Epub 2006 Aug 28.
Pubmed: 16940161
Mascaro C, Buesa C, Ortiz JA, Haro D, Hegardt FG: Molecular cloning and tissue expression of human mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. Arch Biochem Biophys. 1995 Mar 10;317(2):385-90. doi: 10.1006/abbi.1995.1178.
Pubmed: 7893153
Boukaftane Y, Mitchell GA: Cloning and characterization of the human mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase gene. Gene. 1997 Aug 22;195(2):121-6. doi: 10.1016/s0378-1119(97)00067-x.
Pubmed: 9305755
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
Mitchell GA, Robert MF, Hruz PW, Wang S, Fontaine G, Behnke CE, Mende-Mueller LM, Schappert K, Lee C, Gibson KM, Miziorko HM, et al.: 3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human and chicken liver HL cDNAs and characterization of a mutation causing human HL deficiency. J Biol Chem. 1993 Feb 25;268(6):4376-81.
Pubmed: 8440722
Kassovska-Bratinova S, Fukao T, Song XQ, Duncan AM, Chen HS, Robert MF, Perez-Cerda C, Ugarte M, Chartrand C, Vobecky S, Kondo N, Mitchell GA: Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA cloning, human chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient. Am J Hum Genet. 1996 Sep;59(3):519-28.
Pubmed: 8751852
Fukao T, Mitchell GA, Song XQ, Nakamura H, Kassovska-Bratinova S, Orii KE, Wraith JE, Besley G, Wanders RJ, Niezen-Koning KE, Berry GT, Palmieri M, Kondo N: Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene, tertiary structural modeling of the human SCOT monomer, and characterization of three pathogenic mutations. Genomics. 2000 Sep 1;68(2):144-51. doi: 10.1006/geno.2000.6282.
Pubmed: 10964512
Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. doi: 10.1038/nature02919.
Pubmed: 15372022
Marks AR, McIntyre JO, Duncan TM, Erdjument-Bromage H, Tempst P, Fleischer S: Molecular cloning and characterization of (R)-3-hydroxybutyrate dehydrogenase from human heart. J Biol Chem. 1992 Aug 5;267(22):15459-63.
Pubmed: 1639787
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
Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22.
Pubmed: 24275569
Garcia CK, Li X, Luna J, Francke U: cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12. Genomics. 1994 Sep 15;23(2):500-3. doi: 10.1006/geno.1994.1532.
Pubmed: 7835905
van Hasselt PM, Ferdinandusse S, Monroe GR, Ruiter JP, Turkenburg M, Geerlings MJ, Duran K, Harakalova M, van der Zwaag B, Monavari AA, Okur I, Sharrard MJ, Cleary M, O'Connell N, Walker V, Rubio-Gozalbo ME, de Vries MC, Visser G, Houwen RH, van der Smagt JJ, Verhoeven-Duif NM, Wanders RJ, van Haaften G: Monocarboxylate transporter 1 deficiency and ketone utilization. N Engl J Med. 2014 Nov 13;371(20):1900-7. doi: 10.1056/NEJMoa1407778.
Pubmed: 25390740
Williams AL, Jacobs SB, Moreno-Macias H, Huerta-Chagoya A, Churchhouse C, Marquez-Luna C, Garcia-Ortiz H, Gomez-Vazquez MJ, Burtt NP, Aguilar-Salinas CA, Gonzalez-Villalpando C, Florez JC, Orozco L, Haiman CA, Tusie-Luna T, Altshuler D: Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature. 2014 Feb 6;506(7486):97-101. doi: 10.1038/nature12828. Epub 2013 Dec 25.
Pubmed: 24390345
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