Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Ubiquinone Biosynthesis
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2013-08-01
Last Updated: 2022-10-13
Ubiquinone is also known as coenzyme Q10. It is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the isoprenyl chemical subunits. Ubiquinone is a carrier of hydrogen atoms (protons plus electrons) and functions as an ubiquitous coenzyme in redox reactions, where it is first reduced to the enzyme-bound intermediate radical semiquinone and in a second reduction to ubiquinol (Dihydroquinone; CoQH2). Ubiquinone is not tightly bound or covalently linked to any known protein complex but is very mobile. In eukaryotes ubiquinones were found in the inner mito-chondrial membrane and in other membranes such as the endoplasmic reticulum, Golgi vesicles, lysosomes and peroxisomes. The benzoquinone portion of Coenzyme Q10 is synthesized from tyrosine, whereas the isoprene sidechain is synthesized from acetyl-CoA through the mevalonate pathway. The mevalonate pathway is also used for the first steps of cholesterol biosynthesis. The enzyme para-hydroxybenzoate polyprenyltransferase catalyzes the condensation of p-hydroxybenzoate with polyprenyl diphosphate to generate ubiquinone.
References
Ubiquinone Biosynthesis 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.
Wang Y, Oxer D, Hekimi S: Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis. Nat Commun. 2015 Mar 6;6:6393. doi: 10.1038/ncomms7393.
Pubmed: 25744659
Forsgren M, Attersand A, Lake S, Grunler J, Swiezewska E, Dallner G, Climent I: Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ. Biochem J. 2004 Sep 1;382(Pt 2):519-26. doi: 10.1042/BJ20040261.
Pubmed: 15153069
Lopez-Martin JM, Salviati L, Trevisson E, Montini G, DiMauro S, Quinzii C, Hirano M, Rodriguez-Hernandez A, Cordero MD, Sanchez-Alcazar JA, Santos-Ocana C, Navas P: Missense mutation of the COQ2 gene causes defects of bioenergetics and de novo pyrimidine synthesis. Hum Mol Genet. 2007 May 1;16(9):1091-7. doi: 10.1093/hmg/ddm058. Epub 2007 Mar 20.
Pubmed: 17374725
Desbats MA, Morbidoni V, Silic-Benussi M, Doimo M, Ciminale V, Cassina M, Sacconi S, Hirano M, Basso G, Pierrel F, Navas P, Salviati L, Trevisson E: The COQ2 genotype predicts the severity of coenzyme Q10 deficiency. Hum Mol Genet. 2016 Oct 1;25(19):4256-4265. doi: 10.1093/hmg/ddw257. Epub 2016 Aug 4.
Pubmed: 27493029
Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A: Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. 2001 Mar;11(3):422-35. doi: 10.1101/gr.gr1547r.
Pubmed: 11230166
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
Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. doi: 10.1038/nature02055.
Pubmed: 14574404
Heeringa SF, Chernin G, Chaki M, Zhou W, Sloan AJ, Ji Z, Xie LX, Salviati L, Hurd TW, Vega-Warner V, Killen PD, Raphael Y, Ashraf S, Ovunc B, Schoeb DS, McLaughlin HM, Airik R, Vlangos CN, Gbadegesin R, Hinkes B, Saisawat P, Trevisson E, Doimo M, Casarin A, Pertegato V, Giorgi G, Prokisch H, Rotig A, Nurnberg G, Becker C, Wang S, Ozaltin F, Topaloglu R, Bakkaloglu A, Bakkaloglu SA, Muller D, Beissert A, Mir S, Berdeli A, Varpizen S, Zenker M, Matejas V, Santos-Ocana C, Navas P, Kusakabe T, Kispert A, Akman S, Soliman NA, Krick S, Mundel P, Reiser J, Nurnberg P, Clarke CF, Wiggins RC, Faul C, Hildebrandt F: COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness. J Clin Invest. 2011 May;121(5):2013-24. doi: 10.1172/JCI45693. Epub 2011 Apr 11.
Pubmed: 21540551
Zhang K, Lin JW, Wang J, Wu X, Gao H, Hsieh YC, Hwu P, Liu YR, Su L, Chiou HY, Wang D, Yuan YC, Whang-Peng J, Chiu WT, Yen Y: A germline missense mutation in COQ6 is associated with susceptibility to familial schwannomatosis. Genet Med. 2014 Oct;16(10):787-92. doi: 10.1038/gim.2014.39. Epub 2014 Apr 24.
Pubmed: 24763291
Gigante M, Diella S, Santangelo L, Trevisson E, Acosta MJ, Amatruda M, Finzi G, Caridi G, Murer L, Accetturo M, Ranieri E, Ghiggeri GM, Giordano M, Grandaliano G, Salviati L, Gesualdo L: Further phenotypic heterogeneity of CoQ10 deficiency associated with steroid resistant nephrotic syndrome and novel COQ2 and COQ6 variants. Clin Genet. 2017 Aug;92(2):224-226. doi: 10.1111/cge.12960. Epub 2017 Mar 22.
Pubmed: 28044327
Nguyen TP, Casarin A, Desbats MA, Doimo M, Trevisson E, Santos-Ocana C, Navas P, Clarke CF, Salviati L: Molecular characterization of the human COQ5 C-methyltransferase in coenzyme Q10 biosynthesis. Biochim Biophys Acta. 2014 Nov;1841(11):1628-38. doi: 10.1016/j.bbalip.2014.08.007. Epub 2014 Aug 23.
Pubmed: 25152161
Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. doi: 10.1186/1471-2164-8-399.
Pubmed: 17974005
Lohman DC, Forouhar F, Beebe ET, Stefely MS, Minogue CE, Ulbrich A, Stefely JA, Sukumar S, Luna-Sanchez M, Jochem A, Lew S, Seetharaman J, Xiao R, Wang H, Westphall MS, Wrobel RL, Everett JK, Mitchell JC, Lopez LC, Coon JJ, Tong L, Pagliarini DJ: Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis. Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):E4697-705. doi: 10.1073/pnas.1413128111. Epub 2014 Oct 22.
Pubmed: 25339443
Freyer C, Stranneheim H, Naess K, Mourier A, Felser A, Maffezzini C, Lesko N, Bruhn H, Engvall M, Wibom R, Barbaro M, Hinze Y, Magnusson M, Andeer R, Zetterstrom RH, von Dobeln U, Wredenberg A, Wedell A: Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid. J Med Genet. 2015 Nov;52(11):779-83. doi: 10.1136/jmedgenet-2015-102986. Epub 2015 Jun 17.
Pubmed: 26084283
Asaumi S, Kuroyanagi H, Seki N, Shirasawa T: Orthologues of the Caenorhabditis elegans longevity gene clk-1 in mouse and human. Genomics. 1999 Jun 15;58(3):293-301. doi: 10.1006/geno.1999.5838.
Pubmed: 10373327
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
Settings