Coenzyme Q10: Biological Activitiy and Current Approach on the Effect on Health

Abstract

Coenzyme Q₁₀ is an endogenously synthesized and lipid-soluble benzoquinone compound. To date the role in mitochondrial energy production and its antioxidant properties are the well-known activities of coenzyme Q₁₀. In addition, it is stated that coenzyme Q₁₀ has important roles in cell growth and in the control of apoptosis in the case of cellular redox, in which it functions in cell signaling and gene expression. Because of these biological activities, it is associated with a number of diseases such as high blood pressure, diabetes, cancer and cardiovascular disease and also it is effective in the treatment of some neurodegenerative diseases such as alzheimer and parkinson. It has been reported that the dietary intake of coenzyme Q₁₀, which decreases especially in tissues with aging, is inadequate. Experimental and observational studies are needed to understand the role of vitamin in the pathology of diseases and their prevention. In this review article, it is aimed to evaluate the health effects of coenzyme Q₁₀ according to current studies.

Keywords

• coenzyme Q10,ubiquinon,energy coupling,lipid soluble antioxidants,mitochondrial diseases

Koenzim Q10 : Biyolojik Aktivitesi ve Sağlık Üzerine Etkisine Güncel Bakış

Abstract

Koenzim Q₁₀, endojen olarak sentezlenen ve yağda çözünen bir benzokinon bileşiğidir. Mitokondrial enerji üretimindeki görevi ve antioksidan özelliği koenzim Q₁₀’nin bugüne kadar en iyi bilinen fonksiyonlarıdır. Ayrıca koenzim Q₁₀’nin hücre sinyalizasyonunda ve gen ekspresyonunda görev aldığı, hücresel redoks reaksiyonlarında, hücre büyümesi ve apoptozisin kontrolünde de önemli görevleri olduğu belirtilmiştir. Bu biyolojik aktiviteleri nedeniyle kalp sağlığı, yüksek tansiyon, diyabet ve kanser gibi hastalıkların tedavisinde yardımcı olarak kullanılmakta, ayrıca alzheimer ve parkinson gibi bazı nörodejeneratif hastalıkların tedavisinde de etkili olduğu bildirilmiştir. Özellikle yaşlanma ile beraber dokularda azalan koenzim Q₁₀ miktarının diyetle birlikte alımının yetersiz olduğu bildirilmiştir. Hastalıkların patolojisinde vitaminin rolü ve önlenmesine yönelik mekanizmaların anlaşılması için deneysel ve gözlemsel çalışmalara ihtiyaç duyulmaktadır. Bu derleme yazıda koenzim Q₁₀’nin sağlık üzerine etkilerinin güncel çalışmalara göre değerlendirilmesi amaçlanmıştır.  

Keywords

• koenzim Q10,ubikinon,enerji üretimi,mitokondrial hastalıklar

References

1. Abdollahzad, H., Aghdashi, M.A., Jafarabadi, M.A., Alipour, B. (2015). Effects of Coenzyme Q 10 Supplementation on Inflammatory Cytokines (TNF-α, IL-6) and Oxidative Stress in Rheumatoid Arthritis Patients: A Randomized Controlled Trial. Archives of medical research, 46(7), 527-533. doi: 10.1016/j.arcmed.2015.08.006
2. Abdollahzad, H., Alipour, B., Aghdashi, M.A., Jafarabadi, M.A. (2015). Coenzyme Q 10 supplementation in patients with rheumatoid arthritis: Are there any effects on cardiovascular risk factors? European Journal of Integrative Medicine, 7(5):534-539. doi: 10.1016/j.eujim.2015.09.003
3. Acosta, M.J., Fonseca, L.V., Desbats, M.A., Cerqua, C., Zordan, R., Trevisson, E., ve diğerleri. (2016). Coenzyme Q biosynthesis in health and disease. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1857(8), 1079-1085. doi:10.1016/j.bbabio.2016.03.036
4. Alcázar-Fabra, M., Navas, P., Brea-Calvo, G. (2016). Coenzyme Q biosynthesis and its role in the respiratory chain structure. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1857(8), 1073-1078. doi:10.1016/j.bbabio.2016.03.010
5. Alcocer-Gómez, E., Cano-García, F.J., Cordero, M.D. (2013). Effect of coenzyme Q 10 evaluated by 1990 and 2010 ACR Diagnostic Criteria for Fibromyalgia and SCL-90-R: Four case reports and literature review. Nutrition, 29(11), 1422-1425. doi: 10.1016/j.nut.2013.05.005 Barroso, M.P., Gómez-Díaz, C., Villalba, J.M., Burón, M.I., López-Lluch, G., Navas P. (1997). Plasma membrane ubiquinone controls ceramide production and prevents cell death induced by serum withdrawal. Journal of bioenergetics and biomembranes, 29(3), 259-267.
6. Baysal, A., Aksoy, M., Besler, H., Bozkurt, N., Keçecioğlu, S., Merdol, T., ve diğerleri. (2008). Diyet El Kitabı. 5. baskı. Ankara: Hatipoğlu Yayınevi.
7. Bello, R.I., Kagan, V.E., Tyurin, V., Navarro, F., Alcaín, F.J., Villalba, J.M. (2003). Regeneration of lipophilic antioxidants by NAD (P) H: quinone oxidoreductase 1. Protoplasma, 221(1), 129-135. doi:10.1007/s00709-002-0068-x
8. Bentinger, M., Tekle, M., Dallner, G. (2010). Coenzyme Q–biosynthesis and functions. Biochemical and biophysical research communications, 396(1), 74-79. doi:10.1016/j.bbrc.2010.02.147

9. Burke, B.E., Neuenschwander, R., Olson, R.D. (2001). Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. Southern medical journal, 94(11), 1112-1117.
10. Butterfield, D.A. (2004). Proteomics: a new approach to investigate oxidative stress in Alzheimer's disease brain. Brain research, 1000(1):1-7. doi:10.1016/j.brainres.2003.12.012
11. Cordero, M.D., Alcocer-Gómez, E., de Miguel, M., Culic, O., Carrión, A.M., Alvarez-Suarez, J.M., ve diğerleri. (2013). Can coenzyme q10 improve clinical and molecular parameters in fibromyalgia? Antioxidants & Redox Signaling, 19(2), 1356-1361. doi: 10.1089/ars.2013.5260
12. Cordero, M.D., Cotán, D., del-Pozo-Martín, Y., Carrión, A.M., de Miguel, M., Bullón, P., ve diğerleri. (2012). Oral coenzyme Q10 supplementation improves clinical symptoms and recovers pathologic alterations in blood mononuclear cells in a fibromyalgia patient. Nutrition, 28(11), 1200-1203. doi: 10.1016/j.nut.2012.03.018
13. Cordero, M.D., Díaz-Parrado, E., Carrión, A.M., Alfonsi, S., Sánchez-Alcazar, J.A., Bullón, P., ve diğerleri. (2013). Is inflammation a mitochondrial dysfunction-dependent event in fibromyalgia? Antioxidants & Redox Signaling, 18(7), 800-807. doi: 10.1089/ars.2012.4892
14. Crane, F.L. (2001). Biochemical functions of coenzyme Q10. Journal of the American College of Nutrition, 20(6), 591-598. doi:10.1080/07315724.2001.10719063 Dallner, G., Sindelar, P.J. (2000). Regulation of ubiquinone metabolism. Free Radical Biology and Medicine, 29(3), 285-294. doi:10.1016/S0891-5849(00)00307-5
15. de Grey, A.D.N.J. (2001). A proposed mechanism for the lowering of mitochondrial electron leak by caloric restriction. Mitochondrion, 1(2), 129-139. doi:10.1016/S1567-7249(01)00008-3
16. Ernster, L., Dallner, G. (1995). Biochemical, physiological and medical aspects of ubiquinone function. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1271(1):195-204.
17. Fan, L., Feng, Y., Chen, G.C., Qin, L.Q., Fu, C.l., Chen, L.H. (2017). Effects of coenzyme Q10 supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials. Pharmacological research, 119(2017), 128-136. doi:10.1016/j.phrs.2017.01.032
18. Folkers, K., Vadhanavikit, S., Mortensen, S.A. (1985). Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proceedings of the National Academy of Sciences, 82(3), 901-904. doi:10.1073/pnas.82.3.901
19. Fotino, A.D., Thompson-Paul, A.M., Bazzano, L.A. (2012). Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. The American journal of clinical nutrition, 97(2), 268-275. doi:10.3945/ajcn.112.040741
20. Frei, B., Kim, M.C., Ames, B.N. (1990). Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proceedings of the National Academy of Sciences, 87(12), 4879-4883.
21. Gómez-Díaz, C., Rodríguez-Aguilera, J.C., Barroso, M.P., Villalba, J.M., Navarro, F., Crane, F.L., ve diğerleri. (1997). Antioxidant ascorbate is stabilized by NADH-coenzyme Q 10 reductase in the plasma membrane. Journal of bioenergetics and biomembranes, 29(3), 251-257.
22. González, R., Ferrín, G., Hidalgo, A.B., Ranchal, I., López-Cillero, P., Santos-Gónzalez, M., ve diğerleri. (2009). N-acetylcysteine, coenzyme Q 10 and superoxide dismutase mimetic prevent mitochondrial cell dysfunction and cell death induced by d-galactosamine in primary culture of human hepatocytes. Chemico-biological interactions, 181(1), 95-106. doi:10.1016/j.cbi.2009.06.003
23. Gvozdjáková, A., Kucharská, J., Dubravicky, J., Mojto, V., Singh, R.B. (2015).Coenzyme Q10, α-tocopherol, and oxidative stress could be important metabolic biomarkers of male infertility. Disease markers, 2015. doi: 10.1155/2015/827941
24. Hebert, L.E., Beckett, L.A., Scherr, P.A., Evans, D.A. (2001). Annual incidence of Alzheimer disease in the United States projected to the years 2000 through 2050. Alzheimer Disease & Associated Disorders, 15(4), 169-173. doi:10.5014/ajot.2011.002634
25. Hershey, A.D., Powers, S.W., Vockell, A.L.B., LeCates, S.L., Ellinor, P.L., Segers, A., ve diğerleri. (2007). Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache: the journal of head and face pain, 47(1):73-80. doi:10.1111/j.1526-4610.2007.00652.x
26. Hidaka, T., Fujii, K., Funahashi, I., Fukutomi, N., Hosoe, K. (2008). Safety assessment of coenzyme Q10 (CoQ10). Biofactors, 32(1-4):199-208. doi:10.1002/biof.5520320124
27. Kaltschmidt, B., Sparna, T., Kaltschmidt, C. (1999). Activation of NF-κ B by reactive oxygen intermediates in the nervous system. Antioxidants & redox signaling, 1(2), 129-144. doi:10.1089/ars.1999.1.2-129
28. López-Lluch, G., Rodríguez-Aguilera, J.C., Santos-Ocana, C., Navas, P. (2010). Is coenzyme Q a key factor in aging? Mechanisms of ageing and development, 131(4), 225-235. doi:10.1016/j.mad.2010.02.003
29. Mataix, J., Manas, M., Quiles, J., Battino, M., Cassinello, M., Lopez-Frias, M., ve diğerleri. (1997). Coenzyme Q content depends upon oxidative stress and dietary fat unsaturation. Molecular aspects of medicine, 18(Suppl), 129-135.
30. Mitchell, P. Protonmotive redox mechanism of the cytochrome b-c1 complex in the respiratory chain: protonmotive ubiquinone cycle. (1975). FEBS letters, 56(1), 1-6. doi:10.1016/0014-5793(75)80098-6
31. Molyneux, S.L., Florkowski, C.M., George, P.M., Pilbrow, A.P., Frampton, C.M., Lever, M., ve diğerleri. (2008). Coenzyme Q 10: an independent predictor of mortality in chronic heart failure. Journal of the American College of Cardiology, 52(18), 1435-1441. doi:10.1016/j.jacc.2008.07.044
32. Mortensen, S.A., Rosenfeldt, F., Kumar, A., Dolliner, P., Filipiak, K.J., Pella, D., ve diğerleri. (2014). The effect of coenzyme Q 10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC: Heart Failure, 2(6):641-649. doi:10.1016/j.jchf.2014.06.008
33. Munkholm, H., Hansen, H., Rasmussen, K. (1999). Coenzyme Q(10) treatment in serious heart failure. Biofactors, 9(2‐4), 285-289.
34. Navarro, F., Arroyo, A., Martín, S.F., Bello, R.I., De Cabo R, Burgess, J.R., ve diğerleri. (1999). Protective role of ubiquinone in vitamin E and selenium‐deficient plasma membranes. Biofactors, 9(2‐4), 163-170. doi:10.1002/biof.5520090211
35. Overvad, K., Diamant, B., Holm, L., Hølmer, G., Mortensen, S., Stender, S. (1999). Coenzyme Q 10 in health and disease. European Journal of Clinical Nutrition, 53(10), 764-770.
36. Rosenfeldt, F., Haas, S., Krum, H., Hadj, A., Ng, K., Leong, J.Y., ve diğerleri. (2007). Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. Journal of human hypertension, 21(4), 297-306. doi:10.1016/j.eujim.2015.09.134
37. Sandor, P.S., Di Clemente, L., Coppola, G., Saenger, U., Fumal, A., Magis, D., ve diğerleri. (2005). Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology, 64(4), 713-715. doi:10.1212/01.WNL.0000151975.03598.ED
38. Santesso, N.A. Summary of a Cochrane Review: Co-enzyme Q10 supplements to prevent cardiovascular disease. (2015). European journal of integrative medicine. 7(5), 467-468. doi:10.1016/j.eujim.2015.09.134
39. Santos, G.C.D, Antunes, L.M.G., Santos, A.C.D, Bianchi, M.L.P. (2009). Coenzyme Q10 and its effects in the treatment of neurodegenerative diseases. Brazilian Journal of Pharmaceutical Sciences, 45(4):607-618. doi:10.1590/S1984-82502009000400002
40. Singh, R., Niaz, M., Rastogi, S., Shukla, P., Thakur, A. (1999). Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. Journal of human hypertension, 13(3), 203-208. doi:10.1038/sj.jhh.1000778
41. Sohal, R.S., Forster, M.J. (2007). Coenzyme Q, oxidative stress and aging. Mitochondrion, 7(Suppl), 103-111. doi:10.1016/j.mito.2007.03.006
42. Tirabassi, G., Vignini, A., Tiano, L., Buldreghini, E., Brugè, F., Silvestri, S., ve diğerleri. (2015). Protective effects of coenzyme Q10 and aspartic acid on oxidative stress and DNA damage in subjects affected by idiopathic asthenozoospermia. Endocrine, 49(2), 549-552. doi: 10.1007/s12020-014-0432-6
43. Trongtorsak, A., Kongnatthasate, K., Susantitaphong, P., Kittipibul, V., Ariyachaipanich, A. (2017). Effect of coenzyme q10 on left ventrıcular remodelıng and mortalıty ın patıents wıth heart faılure: a meta-analysıs. Journal of the American College of Cardiology, 69(11), 707. doi:10.1016/S0735-1097(17)34096-2
44. Turunen, M., Olsson, J., Dallner, G. (2004). Metabolism and function of coenzyme Q. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1660(1),171-199. doi:10.1016/j.bbamem.2003.11.012
45. Varela-López, A., Giampieri, F., Battino, M., Quiles, J.L. (2016). Coenzyme Q and its role in the dietary therapy against aging. Molecules, 21(3), 373. doi:10.3390/molecules21030373
46. Villalba, J.M., Parrado, C., Santos-Gonzalez, M., Alcain, F.J. (2010). Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations. Expert opinion on investigational drugs, 19(4), 535-554. doi:10.1517/13543781003727495
47. Watson, P.S., Scalia, G.M., Galbraith, A., Burstow, D.J., Bett, N., Aroney, C.N. (1999). Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. Journal of the American College of Cardiology, 33(6), 1549-1552. doi:10.1016/S0735-1097(99)00064-9
48. Watts, G., Playford, D., Croft, K., Ward, N., Mori, T., Burke, V. (2002). Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus. Diabetologia, 45(3), 420-426. doi:10.1007/s00125-001-0760-y
49. Wolf, D.E., Hoffman, C.H., Trenner, N.R., Arison, B.H., Shunk, C.H., Linn, B.O. ve diğerleri. (1958). Coenzyme QI Structure studies on the coenzyme Q group. Journal of the American Chemical Society, 80(17):4752-4752. doi:10.10a21/ja01550a096
50. Wolfe, F., Smythe, H.A., Yunus, M.B., Bennett, R.M., Bombardier, C., Goldenberg, D.L., ve diğerleri. (1990). The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Arthritis & Rheumatology, 33(2):160-172. doi:10.1002/art.1780330203
51. Yoritaka, A., Kawajiri, S., Yamamoto, Y., Nakahara, T., Ando, M., Hashimoto, K., ve diğerleri. (2015). Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q 10 for Parkinson's disease. Parkinsonism & related disorders, 21(8):911-916. doi:10.1016/j.parkreldis.2015.05.022
52. Zhu, Z.G., Sun, M.X., Zhang, W.L., Wang, W.W., Jin, Y.M., Xie, C.L. (2017). The efficacy and safety of coenzyme Q10 in Parkinson’s disease: a meta-analysis of randomized controlled trials. Neurological Sciences, 38(2), 215-224. doi:10.1007/s10072-016-2757-9