MetaCyc Pathway: ubiquinol-10 biosynthesis (eukaryotic)
Inferred from experimentTraceable author statement to experimental support

Enzyme View:

Pathway diagram: ubiquinol-10 biosynthesis (eukaryotic)

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: Q10 biosynthesis, ubiquinone-10 biosynthesis (eukaryotic)

Superclasses: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisQuinol and Quinone BiosynthesisUbiquinol Biosynthesis

Some taxa known to possess this pathway include : Agrius cingulata, Amauroascus aureus, Aphanoascus hispanicus, Aphanoascus saturnoideus, Aphanoascus terreus, Aphanoascus verrucosus, Bos taurus, Chrysosporium keratinophilum, Coccinella, Dichotomomyces cejpii, Gallus gallus, Graphiola phoenicis, Homo sapiens, Ipomoea batatas, Medicago sativa, Monascus pilosus, Monascus purpureus, Monascus ruber, Myxotrichum chartarum, Myxotrichum stipitatum, Neogymnomyces demonbreunii, Neurospora crassa, Ovis aries, Rana catesbeiana, Schizosaccharomyces pombe, Solanum tuberosum, Sphinx ligustri, Spinacia oleracea, Sus scrofa, Tilletia caries, Ustilago cynodontis, Ustilago hordei, Ustilago maydis, Ustilago nuda, Ustilago sphaerogena, Ustilago syntherismae, Zea mays

Expected Taxonomic Range: Eukaryota

General Background

Ubiquinone (also known as coenzyme Q) is an isoprenoid quinone that functions as an electron carrier in membranes. In eukaryotes ubiquinone is found mostly within the inner mitochondrial membrane, where it functions in respiratory electron transport, transferring two electrons from either complex I (NADH dehydrogenase) or complex II (succinate-ubiquinone reductase) to complex III (bc1 complex). The quinone nucleus of ubiquinone is derived directly from 4-hydroxybenzoate, while the isoprenoid subunits of the polyisoprenoid tail are synthesized via the methylerythritol phosphate pathway I, which feeds isoprene units into the Polyprenyl Biosynthesis pathways.

The number of isoprenoid subunits in the ubiquinone side chain vary in different species. For example, Saccharomyces cerevisiae has 6 such subunits, Escherichia coli K-12 has 8, rat and mouse have 9, and Homo sapiens has 10. The ubiquinones are often named according to the number of carbons in the side chain (e.g. ubi-30) or the number of isoprenoid subunits (e.g. Q-10).

Following addition of the polyprenyl tail, the product (4-hydroxy-3-polyprenylbenzoate), is processed in three steps, namely decarboxylation, oxidation, and methylation. The prokaryotic and eukaryotic pathways differ in the order of these steps: in eukaryotes the compound is oxidized and methylated prior to decarboxylation; in prokaryotes the compound is first decarboxylated, followed by oxidation and methylation [Shepherd96].

The ubiquinone biosynthesis pathway has been elucidated primarily by the use of mutant strains that accumulate pathway intermediates; some of the enzymes in this pathway have not been biochemically characterized.

About This Pathway

ubiquinone-10 (Q-10) is the main quinone in many eukaryotic organisms, including humans.

Lower eukaryotes that were reported to contain Q-10 include the mold Neurospora crassa [Lester59], the fission yeast Schizosaccharomyces pombe [Suzuki97, Saiki03], many species of smut fungi from the genus Ustilago and related species, such as Graphiola phoenicis and Tilletia caries [Sugiyama88], and fungi belonging to the orders Onygenales and Eurotiales [Kuraishi00].

Higher eukaryotes that are known to synthesize Q-10 include green plants, such as Spinacia oleracea (spinach), Medicago sativa (alfalfa), Solanum tuberosum (potato) and Zea mays (corn) [Lester59], insects, such as the Lepitopteran Sphinx ligustri, the hawk-moth Agrius cingulata and the Cleopteran Coccinella [Heller60], amphibians (such as the bull frog Rana catesbeiana) [Lester59], birds (such as the chicken Gallus gallus) [Lester59], and mammals, including Bos taurus (cow), Ovis aries (sheep), Sus scrofa (pig) and humans [Lester59].

For the biosynthesis of Q-10 in prokaryotes, see ubiquinol-10 biosynthesis (prokaryotic).

Created 27-Mar-2008 by Caspi R, SRI International


Heller60: Heller, J., Szarkowska, L., Michalek, H. (1960). "Ubiquinone (coenzyme Q) in insects." Nature 188;491. PMID: 13713121

Kuraishi00: Kuraishi H, Itoh M, Katayama Y, Ito T, Hasegawa A, Sugiyama J (2000). "Ubiquinone systems in fungi. V. Distribution and taxonomic implications of ubiquinones in Eurotiales, Onygenales and the related plectomycete genera, except for Aspergillus, Paecilomyces, Penicillium, and their related teleomorphs." Antonie Van Leeuwenhoek 77(2);179-86. PMID: 10768477

Lester59: Lester, R.L., Crane, F.L. (1959). "The natural occurrence of coenzyme Q and related compounds." J Biol Chem 234(8);2169-75. PMID: 13673033

Quinzii06: Quinzii C, Naini A, Salviati L, Trevisson E, Navas P, Dimauro S, Hirano M (2006). "A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency." Am J Hum Genet 78(2);345-9. PMID: 16400613

Saiki03: Saiki R, Nagata A, Uchida N, Kainou T, Matsuda H, Kawamukai M (2003). "Fission yeast decaprenyl diphosphate synthase consists of Dps1 and the newly characterized Dlp1 protein in a novel heterotetrameric structure." Eur J Biochem 270(20);4113-21. PMID: 14519123

Shepherd96: Shepherd, J. A., Poon, W. W., Myles, D. C., Clarke, C. F. (1996). "The biosynthesis of ubiquinone: synthesis and enzymatic modification of biosynthetic precursors." Tetrahedron Lett. 37(14):2395-2398.

Sugiyama88: Sugiyama, J., Itoh, M., Katayama, Y., Yamaoka, Y., Ando, K., Kakishima, M., Kuraishi, H. (1988). "Ubiquinone systems in fungi II. Distribution of ubiquinones in smut and rust fungi." Mycologia 80(1):115-120.

Suzuki97: Suzuki K, Okada K, Kamiya Y, Zhu XF, Nakagawa T, Kawamukai M, Matsuda H (1997). "Analysis of the decaprenyl diphosphate synthase (dps) gene in fission yeast suggests a role of ubiquinone as an antioxidant." J Biochem 121(3);496-505. PMID: 9133618

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Appelkvist94: Appelkvist EL, Aberg F, Guan Z, Parmryd I, Dallner G (1994). "Regulation of coenzyme Q biosynthesis." Mol Aspects Med 15 Suppl;s37-46. PMID: 7752843

Asaumi99: Asaumi S, Kuroyanagi H, Seki N, Shirasawa T (1999). "Orthologues of the Caenorhabditis elegans longevity gene clk-1 in mouse and human." Genomics 58(3);293-301. PMID: 10373327

Ashraf13: Ashraf S, Gee HY, Woerner S, Xie LX, Vega-Warner V, Lovric S, Fang H, Song X, Cattran DC, Avila-Casado C, Paterson AD, Nitschke P, Bole-Feysot C, Cochat P, Esteve-Rudd J, Haberberger B, Allen SJ, Zhou W, Airik R, Otto EA, Barua M, Al-Hamed MH, Kari JA, Evans J, Bierzynska A, Saleem MA, Bockenhauer D, Kleta R, El Desoky S, Hacihamdioglu DO, Gok F, Washburn J, Wiggins RC, Choi M, Lifton RP, Levy S, Han Z, Salviati L, Prokisch H, Williams DS, Pollak M, Clarke CF, Pei Y, Antignac C, Hildebrandt F (2013). "ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption." J Clin Invest 123(12);5179-89. PMID: 24270420

Forsgren04: Forsgren M, Attersand A, Lake S, Grunler J, Swiezewska E, Dallner G, Climent I (2004). "Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ." Biochem J 382(Pt 2);519-26. PMID: 15153069

Heeringa11: 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 (2011). "COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness." J Clin Invest 121(5);2013-24. PMID: 21540551

Jonassen00: Jonassen T, Clarke CF (2000). "Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis." J Biol Chem 275(17);12381-7. PMID: 10777520

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Mollet07: Mollet J, Giurgea I, Schlemmer D, Dallner G, Chretien D, Delahodde A, Bacq D, de Lonlay P, Munnich A, Rotig A (2007). "Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders." J Clin Invest 117(3);765-72. PMID: 17332895

MultipleSystem13: Multiple-System Atrophy Research Collaboration (2013). "Mutations in COQ2 in familial and sporadic multiple-system atrophy." N Engl J Med 369(3);233-44. PMID: 23758206

Poon99: Poon WW, Barkovich RJ, Hsu AY, Frankel A, Lee PT, Shepherd JN, Myles DC, Clarke CF (1999). "Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis." J Biol Chem 274(31);21665-72. PMID: 10419476

Rotig00: Rotig A, Appelkvist EL, Geromel V, Chretien D, Kadhom N, Edery P, Lebideau M, Dallner G, Munnich A, Ernster L, Rustin P (2000). "Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency." Lancet 356(9227);391-5. PMID: 10972372

Saiki05: Saiki R, Nagata A, Kainou T, Matsuda H, Kawamukai M (2005). "Characterization of solanesyl and decaprenyl diphosphate synthases in mice and humans." FEBS J 272(21);5606-22. PMID: 16262699

Stenmark01: Stenmark P, Grunler J, Mattsson J, Sindelar PJ, Nordlund P, Berthold DA (2001). "A new member of the family of di-iron carboxylate proteins. Coq7 (clk-1), a membrane-bound hydroxylase involved in ubiquinone biosynthesis." J Biol Chem 276(36);33297-300. PMID: 11435415

Vajo99: Vajo Z, King LM, Jonassen T, Wilkin DJ, Ho N, Munnich A, Clarke CF, Francomano CA (1999). "Conservation of the Caenorhabditis elegans timing gene clk-1 from yeast to human: a gene required for ubiquinone biosynthesis with potential implications for aging." Mamm Genome 10(10);1000-4. PMID: 10501970

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 20.0 (software by SRI International) on Fri May 6, 2016, BIOCYC14.