Ubiquinone. Biosynthesis of quinone ring and its isoprenoid side chain. Intracellular localization.

• Authors: Anna Szkopińska
• Languages of publication: EN

Abstracts

EN

Ubiquinone, known as coenzyme Q, was shown to be the part of the metabolic pathways by Crane et al. in 1957. Its function as a component of the mitochondrial respiratory chain is well established. However, ubiquinone has recently attracted increasing attention with regard to its function, in the reduced form, as an antioxidant. In ubiquinone synthesis the para-hydroxybenzoate ring (which is the derivative of tyrosine or phenylalanine) is condensed with a hydrophobic polyisoprenoid side chain, whose length varies from 6 to 10 isoprene units depending on the organism. para-Hydroxybenzoate (PHB) polyprenyltransferase that catalyzes the condensation of PHB with polyprenyl diphosphate has a broad substrate specificity. Most of the genes encoding (all-E)-prenyltransferases which synthesize polyisoprenoid chains, have been cloned. Their structure is either homo- or heterodimeric. Genes that encode prenyltransferases catalysing the transfer of the isoprenoid chain to para-hydroxybenzoate were also cloned in bacteria and yeast. To form ubiquinone, prenylated PHB undergoes several modifications such as hydroxylations, O-methylations, methylations and decarboxylation. In eukaryotes ubiquinones were found in the inner mitochondrial membrane and in other membranes such as the endoplasmic reticulum, Golgi vesicles, lysosomes and peroxisomes. Still, the subcellular site of their biosynthesis remains unclear. Considering the diversity of functions of ubiquinones, and their multistep biosynthesis, identification of factors regulating their cellular level remains an elusive task.

Keywords

EN

polyisoprenoid diphosphates; ubiquinone; polyprenyltransferases

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2000
• Volume: 47
• Issue: 2
• Pages: 469-480

Dates

published

2000

received

2000-01-19

accepted

2000-05-17

Contributors

author

Anna Szkopińska

• Department of Lipid Biochemistry, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, A. Pawińskiego 5a, 02-106 Warszawa, Poland

References

• 1. Crane, F.L., Hatefi,Y., Lester, R.L. & Widmer, C. (1957) Isolation of a quinone from beef heart mitochondria. Biochim. Biophys. Acta 25, 220-221.
• 2. Wolf, D.E., Hoffman, C.H., Trenner, N.R., Arison, B.H., Shunk, C.H., Linn, B.O., McPherson, J.F. & Folkers, K. (1958) Coenzyme Q. Structure studies on the coenzyme Q group. J. Am. Chem. Soc. 80, 4752-4758.
• 3. Festenstein, G.N., Heaton, F.W., Lowe, J.S. & Morton, R.A. (1955) A constituent of the unsaponificable portion of the animal tissue lipids (λmax 272 mμ;). Biochem. J. 59, 558-566.
• 4. Genova, M.L., Bonacorsi, E., D'Aurelio, M., Formiggini, G., Narudo, B., Cuccomarino, S., Turi, P., Pich, M., Lenaz, G. & Bovina, C. (1999) Protective effect of exogenous coenzyme Q in rats subjected to partial hepatic ischemia and reperfusion. Biofactors 9, 345-349
• 5. Miksovska, J., Schiffer, M., Hanson, D. & Sebban, K. (1999) Proton uptake by bacterial reaction centers: The protein complex responds in a similar manner to the reduction of either quinone acceptor. Proc. Natl. Acad. Sci. U.S.A. 96, 14348-14353.
• 6. Gillman, I., Clark, T., N. & Manderville, R.A. (1999) Oxidation of ochratoxin A by an Fe- porphyrin system: Model for enzymatic activation of DNA cleavage. Chem. Res. Toxicol. 12, 1066-1076.
• 7. Hundal, T., Forsmark, P., Ernster, L. & Andersson, B. (1992) Antioxidant activity of reduced plastoquinone in thylacoid membranes during strong illumination. EBEC Short Reports 7, 6-8.
• 8. Aiyar, A. & Olson, R. (1964) Biosynthesis of the benzoquinone ring of coenzyme Q9 in the rat. Federation Proc. 23, 425.
• 9. Olson, R. (1965) Anabolism of the coenzyme Q family and their biological activities. Federation Proc. 24, 85-92.
• 10. Parson, W. & Rudney, H. (1965) The biosynthesis of ubiquinone and rhodoquinone from p-hydroxybenzoate and p-hydroxybenzaldehyde in Rhodospirillum rubrum. J. Biol. Chem. 240, 1855-1863.
• 11. Olson, R., Dialameh, G. & Bentley, R. (1961) Ciba Fundation Symposium on Quinones in Electron Transport (Welstenholme, G. & O'Connor, C., eds.) London.
• 12. Ramasarma, T. (1985) in Coenzyme Q Biochemistry, Bioenergetics and Clinical Applications of Ubiquinone (Lenaz, G., ed.) pp. 67-81, Wiley, New York.
• 13. Kang, D., Takeshigate, K., Isobe, R. & Minakami, S. (1991) Evidence that the decarboxylation reaction occurs before the first methylation in ubiquinone biosynthesis in rat liver mitochondria. Eur. J. Biochem. 198, 599-605.
• 14. Wu, G., Wiliams, H., Zamanian, M., Gibson, F. & Poole, R. (1992) Isolation and characterization of Escherichia coli mutants affected in aerobic respiration: the cloning and nucleotide sequence of ubiG; identification of an S-adenosylmethionine binding motif in protein, RNA and small-molecule methyltransferases. J. Gen. Microbiol. 138, 2101- 2111.
• 15. Clarke, C., Wiliams, W. & Teruya, J. (1991) Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of coq3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene. J. Biol. Chem. 266, 16636-16644.
• 16. Nakahigashi, K., Miyamoto, K., Nishimura, K. & Inokuchi, H. (1992) Isolation and characterization of a light sensitive mutant of Escherichia coli K-12 with a mutation in a gene that is required for the biosynthesis of ubiquinone. J. Bacteriol. 174, 7352-7359.
• 17. Huang, J., He, Z. & Wiegel, J. (1999) Cloning, characterization, and expression of a novel gene encoding a reversible 4-hydroxybenzoate decarboxylase from Clostridium hydroxybenzoicum. J. Bacteriol. 181, 5119-5122.
• 18. Marbois, B., Hsu, A., Pillai, R., Colicelli, J. & Clarke, C. (1994) Cloning of a rat cDNA encoding dihydroxypolyprenylbenzoate methyltransferase by functional complementation of a Saccharomyces cerevisiae mutant deficient in ubiquinone biosynthesis. Gene 138, 213-217.
• 19. Avelange-Macherel, M.-H. & Joyard, J. (1998) Cloning and functional expression of AtCOQ3, the Arabidopsis homologue of the yeast COQ3 gene, encoding a methyltransferase from plant mitochondria involved in ubiquinone biosynthesis. Plant J. 14, 203-213.
• 20. Lynen, F., Eggerer, H., Henning, U. & Kessel, I. (1958) Angew. Chem. 70, 738-742.
• 21. Chaykin, S., Law, J., Philips, A., Tchen, T. & Bloch, T. (1958) Phosphorylated intermediates in the synthesis of squalene. Proc. Natl. Acad. Sci. U.S.A. 44, 998-1004.
• 22. Rohmer, M., Knani, M., Simonin, P., Sutter, B. & Sahm, H. (1993) Isoprenoid biosynthesis in bacteria: A novel pathway for the early steps leading to isopentenyl diphosphate. Biochem. J. 295, 517-524.
• 23. Rohmer, M., Seeman, M., Horbach, S., Bringer-Mayer, S. & Sahm, H. (1996) Isopentenol pyrophosphate isomerase. J. Am. Chem. Soc. 118, 2564-2566.
• 24. Agranoff, B., Eggerer, H., Henning, U. & Lynen, F. (1959) Isopentenol pyrophosphate isomerase. J. Am. Chem. Soc. 81, 1254-1255.
• 25. Tarshis, L., Proteau, P., Kellogg, B., Sacchettini, J. & Poulter, C. (1996) Regulation of product chain length by isoprenyl diphosphate synthases. Proc. Natl. Acad. Sci. U.S.A. 93, 15018-15023.
• 26. Jeffries, L., Cawthorn, M., Harris, M., Diplock, A., Green, J. & Price, S. (1967) Distribution of menaquinones in aerobic Micrococcaceae. Nature 215, 257-259.
• 27. Fujii, H., Koyama, T. & Ogura, K. (1982) Hexaprenyl pyrophosphate synthetase from Micrococcus luteus B-P 26. J. Biol. Chem. 257, 14610-14612.
• 28. Shimizu, N., Koyama, T. & Ogura, K. (1998) Molecular cloning, expression, and characterization of the two genes encoding the two essential protein components of Micrococcus luteus B-P 26 hexaprenyl diphosphate synthase. J. Bacteriol. 180, 1578-1581.
• 29. Reference in the text as footnote 1.
• 30. Koike-Takeshita, A., Koyama, T. & Ogura, K. (1997) Identification of a novel gene cluster participating in menaquinone (Vitamin K2) biosynthesis. J. Biol. Chem. 272, 12380- 12383.
• 31. Ashby, M. & Edwards, P. (1990) Elucidation of deficiency in two yeast coenzyme Q mutants. J. Biol. Chem. 265, 13157-13164.
• 32. Takahashi, I., Ogura, K. & Seto, S. (1980) Heptaprenyl pyrophosphate synthetase from Bacillus subtilis J. Biol. Chem. 255, 4539- 4543.
• 33. Koike-Takeshita, A., Koyama, T., Obata, S. & Ogura, K. (1995) Molecular cloning and nucleotide sequence of the genes for two essential proteins constituting a novel enzyme for heptaprenyl diphosphate synthesis. J. Biol. Chem. 270, 18396-18400.
• 34. Koyama, T., Obata, S., Osabe, M., Takeshita, A., Yokoyama, K., Uchida, M., Nishino, T. & Ogura, K. (1993) Thermostable farnesyl diphosphate synthase of Bacillus stearothermophilus: Molecular cloning, sequence determination, overproduction, and purification. J. Biochem. 113, 355-363.
• 35. Zang, Y.-W., Koyama, T. & Ogura, K. (1997) Two cistrons of the gerC operon of Bacillus subtilis encode the two subunits of heptaprenyl diphosphate synthase. J. Bacteriol. 179, 1417-1419.
• 36. Fujisaki, S., Nishino, T. & Katsuki, H. (1986) Isoprenoid synthesis in Escherichia coli. Separation and partial purification of four enzymes involved in the synthesis. J. Biochem. 99, 1327-1337.
• 37. Choi, Y., Nishida, T., Kawamukai, M., Utsumi, R., Sakai, H. & Kamono, T. (1989) Cloning and sequencing of an Escherichia coli gene nlp, highly homologous to the ner genes of bacteriophages Mu and D108. J. Bacteriol. 171, 5222-5225.
• 38. Fujisaki, S., Hara, H., Nishimura, Y., Horiuchi, K. & Nishino, T. (1990) Cloning and nucleotide sequence of the ispA gene responsible for farnesyl diphosphate synthase activity in Escherichia coli. J. Biochem. 108, 995-1000.
• 39. Jeong, J., Kitakawa, M. & Isono, K. (1993) Cloning and nucleotide sequencing of the genes, rpIU and rpmA, for ribosomal proteins L21 and L27 of Escherichia coli. DNA Sequence 4, 59-67.
• 40. Asai, K., Fujisaki, S., Nishimura, Y., Nishino, T., Okada, K., Nakagawa, T., Kawamukai, M. & Matsuda, H. (1994) The identification of Escherichia coli ispB (cel) gene encoding the octaprenyl diphosphate synthase. Biochem. Biophys. Res. Commun. 202, 340-345.
• 41. Okada, K., Suzuki, K., Kamiya, Y., Zhu, X., Fujisaki, S., Nishimura, Y., Nishino, T., Nakagawa, T., Kawamukai, M. & Matsuda, H. (1996) Polyprenyl diphosphate synthase essentially defines the length of the side chain of ubiquinone. Biochim. Biophys. Acta 1302, 217-223.
• 42. Sagami, H., Ogura, K. & Seto, S. (1977) Solanesyl pyrophosphate synthase from Micrococcus lysodeikticus. Biochemistry 16, 4616-4622.
• 43. Ohnuma, S., Koyama, T. & Ogura, K. (1991) Purification of solanesyl-diphosphate synthase from Micrococcus luteus. J. Biol. Chem. 266, 23706-23713.
• 44. Ishi, K., Sagami, H. & Ogura, K. (1985) Decaprenyl pyrophosphate synthetase from Paracoccus denitrificans. Biochim. Biophys. Acta 835, 291-297.
• 45. Suzuki, K., Okada, K., Kamiya, Y., Zhu, X., 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, 496-505.
• 46. Reference in the text as footnote 2.
• 47. Swiezewska, E., Dallner, G., Andersson, B. & Ernster, L. (1993) Biosynthesis of ubiquinone and plastoquinone in the endoplasmic reticulum-Golgi membranes of spinach leaves. J. Biol. Chem. 268, 1494-1499.
• 48. Teclebrahn, H., Olsson, J., Swiezewska, E. & Dallner, G. (1993) Biosynthesis of the side chain of ubiquinone: Trans-prenyltransferase in rat liver microsomes. J. Biol. Chem. 268, 23081-23086.
• 49. Runquist, M., Ericsson, J., Thelin, A., Chojnacki, T. & Dallner, G. (1994) Isoprenoid biosynthesis in rat liver mitochondria. Studies on farnesyl pyrophosphate synthase and trans-prenyltransferase. J. Biol. Chem. 269, 5804-5809.
• 50. Drabikowska, A. (1969) Biosynthesis of ubiquinone in animal tissues. Post. Biochem. 15, 397-410 (in Polish).
• 51. Wu, G., Wiliams, H., Gibson, F. & Poole, K. (1993) Mutants of Escherichia coli affected in respiration: The cloning and nucleotide sequence of ubiA, encoding the membrane- bound p-hydroxybenzoate:octaprenyltransferase. J. Gen. Microbiol. 139, 1795-1805.
• 52. Ashby, M., Kutsunai, S., Ackerman, S., Tzagoloff, A. & Edwards, P. (1992) COQ2 is a candidate for the structural gene encoding para-hydroxybenzoate:polyprenyltransferase. J. Biol. Chem. 267, 4128-4136.
• 53. Siebert, M., Bechthold, A., Melzer, M., May, U., Berger, U., Schroder, G., Schroder, J., Severin, K. & Heide, L. (1992) Cloning of the genes coding for chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyl transferase from Escherichia coli. FEBS Lett. 307, 347-350.
• 54. Melzer, M. & Heide, L. (1994) Characterization of polyprenyldiphosphate:4-hydroxybenzoate polyprenyltransferase from Escherichia coli. Biochim. Biophys. Acta 1212, 93-102.
• 55. Lutke-Brinkhaus, F., Liedvogel, B. & Kleinig, H. (1984) On the biosynthesis of ubiquinones in plant mitochondria. Eur. J. Biochem. 141, 537-541.
• 56. Leppik, R., Stroobant, P., Shineberg, B., Young, I. & Gibson, F. (1976) Membrane-associated reactions in ubiquinone biosynthesis. Biochim. Biophys. Acta 428, 146-156.
• 57. Lutke-Brinkhaus, F. & Kleinig, H. (1987) Ubiquinone biosynthesis in plant mitochondria. Methods Enzymol. 148, 486-490.
• 58. Ericsson, J., Runquist, M., Thelin, A., Anderson, M., Chojnacki, T. & Dallner (1993) Distribution of prenyltransferases in rat tissues. J. Biol. Chem. 268, 832-838.
• 59. Aboushadi, N. & Krisans, S. (1998) Analysis of isoprenoid biosynthesis in peroxisomal-deficient Pex2 CHO cell lines. J. Lipid Res. 39, 1781-1791.
• 60. Kalen, A., Norling, B., Appelkvist, E.-L. & Dallner, G. (1987) Ubiquinone biosynthesis by the microsomal fraction from rat liver. Biochim. Biophys. Acta 926, 70-78.
• 61. Engfelt, W., Shackelford, E., Aboushadi, N., Jessani, N., Masuda, K., Paton, V., Keller, G. & Krisans, K. (1997) The characterization of UT-2 cells. The induction of peroxisomal 3-hydroxy-3-methylglutaryl coenzyme A. J. Biol. Chem. 272, 24579-24587.
• 62. Elmberger, G., Kalen, A., Brunk, U. & Dallner, G. (1989) Discharge of newly synthesized dolichol and ubiquinone with lipoproteins to rat liver perfusate and to the bile. Lipids 24, 919-930.
• 63. Szkopińska, A., Świeżewska, E. & Karst, F. (2000) The regulation of activity of main mevalonic acid pathway enzymes: Farnesyl diphosphate synthase, 3-hydroxy-3-methylglutaryl-CoA reductase and squalene synthase in yeast Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 267, 473-477.
• 64. Grabowska, D., Karst, F. & Szkopińska, A. (1998) Effect of squalene synthase gene disruption on synthesis of polyprenols in Saccharomyces cerevisiae. FEBS Lett. 434, 406-408.
• 65. Meganathan, A. (1996) Biosynthesis of the isoprenoid quinones, menaquinone (vitamin K2 ) and ubiquinone (coenzymeQ); in Escherichia coli and Salmonella: Cell. Mol. Biol. (Neidhardt F.C., et al.) pp. 642-656, American Society for Microbiology, Washington.
• 66. Thelin, A., Schedin, S. & Dallner, G. (1992) Half-life of ubiquinone-9 in rat tissues. FEBS Lett. 313, 118-120.
• 67. Andersson, M., Elmberger, P., Edlund, C. Kristensson, K. & Dallner, G. (1990) Rates of cholesterol, ubiquinone, dolichol, and dolichyl-P biosynthesis in rat brain slices. FEBS Lett. 269, 15-18.
• 68. Harman, D. (1988) Free radicals in aging. Mol. Cell. Biochem. 84, 155-61.
• 69. Cutler, R. (1985) Peroxide-producing potential of tissues: Inverse correlation with longevity of mammalian species. Proc. Natl. Acad. Sci. U.S.A. 82, 4798-4802.
• 70. Stadtman, E. & Oliver, C. (1991) Metal-catalyzed oxidation of proteins. Physiological consequences. J. Biol. Chem. 266, 2005-2008.
• 71. Linnane, A., Marzuki, S., Ozawa, T. & Tanaka, M. (1989) Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet 1, 642-645.
• 72. Ozawa, T. (1997) Genetic and functional changes in mitochondria associated with aging. Physiol. Rev. 77, 425-464.
• 73. Lenaz, G., Cavazzoni, M., Genova, M., D'Aurelio, M., Merlo, M., Palloti, F., Formiggini, G., Marchetti, M., Parenti, G. & Bovina, C. (1998) Oxidative stress, antioxidant defences in aging. BioFactors 8, 195-204.
• 74. Soderberg, M., Edlund, K., Kristensson, K. & Dallner, G. (1990) Lipid compositions of different regions of the human brain during aging. J. Neurochem. 54, 415-423.
• 75. Ericsson, J. & Dallner, G. (1993) in Subcellular Biochemistry (Borgese, N. & Harris, J., eds.) vol. 21, pp. 229-272, Plenum, New York.
• 76. Grunler, J., Ericsson, J. & Dallner, G. (1994) Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins. Biochim. Biophys. Acta 1212, 259-277.