Ubiquinol

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Ubiquinol
Ubiquinol structure.png
Identifiers
PubChem9962735
Properties
Molecular formulaC59H92O4
Molar mass865.36 g mol−1
Appearanceoff-white powder
Melting point45.6 C
Solubility in waterpractically insoluble in water
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Infobox references
 
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Ubiquinol
Ubiquinol structure.png
Identifiers
PubChem9962735
Properties
Molecular formulaC59H92O4
Molar mass865.36 g mol−1
Appearanceoff-white powder
Melting point45.6 C
Solubility in waterpractically insoluble in water
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Ubiquinol is an electron-rich (reduced) form of coenzyme Q10.

The natural ubiquinol form of coenzyme Q10 is 2,3-dimethoxy-5-methyl-6-poly prenyl-1,4-benzoquinol, where the polyprenylated side-chain is 9-10 units long in mammals. Coenzyme Q10 (CoQ10) exists in three redox states, fully oxidized (ubiquinone), partially reduced (semiquinone or ubisemiquinone), and fully reduced (ubiquinol). The redox functions of ubiquinol in cellular energy production and antioxidant protection are based on the ability to exchange two electrons in a redox cycle between ubiquinol (reduced) and the ubiquinone (oxidized) form.[1][2]

Ubiquinol is a lipid-soluble benzoquinol that is found in all cellular systems and in nearly every cell, tissue, and organ in mammals. Ubiquinol is acquired through biosynthesis, supplementation, and, in small amounts, diet. Ubiquinol has an established role as an essential component of the electron transport chain transferring electrons resulting in ATP synthesis. In mammals, ATP production takes place predominantly in mitochondria and to a lesser extent in other organelles such as the Golgi apparatus or endoplasmic reticulum. The mitochondria typically produce nearly 95% of the energy required for cellular growth, development, and healthy metabolism. The antioxidant action of ubiquinol is now considered to be one of the most important functions in cellular systems.

Ubiquinol is a potent lipophilic antioxidant capable of regenerating other antioxidants such as tocopherol (Vitamin E) and ascorbate (Vitamin C). Recent studies have also revealed its function in gene expression involved in human cell signaling, metabolism, and transport.[3][4][5][6]

Nutrient function summary[edit]

Ubiquinol is the antioxidant form of CoQ10 and is essential for mitochondrial synthesis of energy. It is the only known lipid-soluble antioxidant that is endogenously synthesized, protecting biological membranes against lipid peroxidation as well as regenerating other antioxidants such as Vitamin C and Vitamin E. Published clinical and experimental research shows that ubiquinol affects cardiovascular health, neuronal metabolism, renal health, and genes related to lipid/lipoprotein metabolism and inflammation.

Energy production[edit]

In terms of its functions, ubiquinol's primary roles are in the synthesis of mitochondrial energy and as a protective antioxidant. The vitamin-like nutrient is found concentrated in the inner mitochondrial membrane, where it serves as a carrier of reducing equivalents in the mitochondrial electron transport chain’s I and II complexes toward complex III. In this process, ubiquinol serves to produce ATP (adenosine triphosphate), the main energy intermediate in living organisms.

Effects and Research[edit]

Cardiovascular effects[edit]

Some studies [7] [8] have considered the effects of ubiquinone (the oxidized, spent form) and ubiquinol (the antioxidant form) on heart failure patients.

Gene expression[edit]

In 2010, researchers from Germany’s University of Kiel and Japan’s Shinshu University published a study examining genome-expression effects of ubiquinol and ubiquinone. With the exception of one gene, ubiquinone did not have any effect on these genes.[9]

Statins[edit]

Initial studies into combined treatment with statins have reported some potential[10] or theoretical benefits.[11] [12]

Antioxidant effects[edit]

Some research has addressed investigated effects of ubiquitol on antioxidant functions.[13][14]

Aging[edit]

Some preliminary information indicates that ubiquinol may be involved in the aging process. [15] [16] [17]

Liver health[edit]

Oral supplementation of ubiquinol at 150 mg per day reduces serum GGT (gamma glutamyltransferase, an enzyme that is a biomarker of liver function and a potential marker of oxidative stress) and downregulates genoexpression of GGT1 mRNA.[18]

Neuronal health[edit]

A number of small studies have shown CoQ10 to benefit the neurological system, which includes the brain. Some benefit was seen in Parkinson's disease.[19] Subsequent larger studies failed to show any benefit.[20]

Oral health[edit]

The ubiquinol form of coenzyme Q10 has been studied specifically for its impact on oral health. [12] [21] [22] Nevertheless, no serious review article has until this day proven any clinical or otherwise therapeutical effects of coenzyme Q10 on periodontal disease or any other oral disease.

Renal health[edit]

Some research in an animal model of chronic kidney disease as been performed. [23]

Male Infertility[edit]

A recent study investigated the effects of the ubiquinol on male infertility. [12] [24]

Gene expression[edit]

Early research has identified multiple genes and pathways that may be related to CoQ10. [25]

Inflammation[edit]

Researchers have investigated the relationship between ubiquitol and the inflammation process. [26]

Bioavailability[edit]

It is well-established that CoQ10 is not well absorbed into the body, as has been published in many peer-reviewed scientific journals.[27] Since the ubiquinol form has two additional hydrogens, it results in the conversion of two ketone groups into hydroxyl groups on the active portion of the molecule. This causes an increase in the polarity of the CoQ10 molecule and may be a significant factor behind the observed enhanced bioavailability of ubiquinol. Taken orally, ubiquinol exhibits greater bioavailability than ubiquinone.[28]

However, there are authorities that dispute whether ubiquinol is more bioavailable in practice rather than in theory compared to CoQ10 supplements because those have their CoQ10 molecules dissolved in lipid micelles, which then deliver their cargo to the plasma membrane in the intestinal wall. There they dissolve via simple diffusion in the intestinal cells, then onto the lymph vessels, and then into the venous system. Since ubiquinol and CoQ10 are redox pairs and can and are rapidly inter-converted in the body, it is not clear that ubiqinol's more hydrophilic nature compared to CoQ10 is of practical significance.[29]

Content in foods[edit]

In foods, there are varying amounts of ubiquinol. An analysis of a range of foods found ubiquinol to be present in 66 out of 70 items and accounted for 46% of the total coenzyme Q10 intake. The following chart is a sample of the results.[30]

FoodUbiquinol (μg/g)Ubiquinone (μg/g)
Beef (shoulder)5.3625
Beef (liver)40.10.4
Pork (shoulder)25.419.6
Pork (thigh)2.6311.2
Chicken (breast)13.83.24
Mackerel0.5210.1
Tuna (canned)14.60.29
Yellowtail20.912.5
Broccoli3.833.17
Parsley5.911.57
Orange0.880.14

Molecular aspects[edit]

Ubiquinol is a benzoquinol and is the reduced product of ubiquinone also called coenzyme Q10. Its tail consists of 10 isoprene units.

Ubiquinol

The reduction of ubiquinone to ubiquinol occurs in Complexes I & II in the electron transfer chain. The Q cycle[31] is a process that occurs in cytochrome b,[32][33] a component of Complex III in the electron transport chain, and that converts ubiquinol to ubiquinone in a cyclic fashion. When ubiquinol binds to cytochrome b, the pKa of the phenolic group decreases so that the proton ionizes and the phenoxide anion is formed.

Ubiquinol, semiphenoxide

If the phenoxide oxygen is oxidized, the semiquinone is formed with the unpaired electron being located on the ring.

Ubiquinol

A page on Proteopedia, Complex III of Electron Transport Chain,[34] contains rotatable 3-D structures of Complex III, which may be used to study the peptide structures of Complex III and the mechanism of the Q cycle.

References[edit]

  1. ^ Mellors, A; Tappel, AL (1966). "The inhibition of mitochondrial peroxidation by ubiquinone and ubiquinol". The Journal of Biological Chemistry 241 (19): 4353–6. PMID 5922959. 
  2. ^ Mellors, A.; Tappel, A. L. (1966). "Quinones and quinols as inhibitors of lipid peroxidation". Lipids 1 (4): 282–4. doi:10.1007/BF02531617. PMID 17805631. 
  3. ^ Battino, Maurizio; Ferri, Elida; Gorini, Antonella; Villa, Roberto Federico; Huertas, Jesus Francisco Rodriguez; Fiorella, Pierluigi; Genova, Maria Luisa; Lenaz, Giorgio; Marchetti, Mario (1990). "Natural Distribution and Occurrence of Coenzyme Q Homologues". Molecular Membrane Biology 9 (3): 179–90. doi:10.3109/09687689009025839. PMID 2135303. 
  4. ^ Green, David E.; Tzagoloff, Alexander (1966). "The mitochondrial electron transfer chain". Archives of Biochemistry and Biophysics 116 (1): 293–304. doi:10.1016/0003-9861(66)90036-1. PMID 4289862. 
  5. ^ Frei, Balz; Kim, Mike C.; Ames, Bruce N. (1990). "Ubiquinol-10 is an Effective Lipid-Soluble Antioxidant at Physiological Concentrations". Proceedings of the National Academy of Sciences of the United States of America 87 (12): 4879–83. Bibcode:1990PNAS...87.4879F. doi:10.1073/pnas.87.12.4879. JSTOR 2354427. PMC 54222. PMID 2352956. 
  6. ^ Arroyo, A.; Navarro, F.; Navas, P.; Villalba, J. M. (1998). "Ubiquinol regeneration by plasma membrane ubiquinone reductase". Protoplasma 205: 107–13. doi:10.1007/BF01279300. 
  7. ^ Langsjoen, Peter H.; Langsjoen, Alena M. (2008). "Supplemental ubiquinol in patients with advanced congestive heart failure". BioFactors 32 (1–4): 119–28. doi:10.1002/biof.5520320114. PMID 19096107. 
  8. ^ Langsjoen, Peter H; Langsjoen, Alena M (27–30 May 2010). "Supplemental Ubiquinol in congestive heart failure: 3 year experience". 6th International Coenzyme Q10 Conference Brussels. pp. 29–30. 
  9. ^ Schmelzer, Constance; Okun, Jürgen G.; Haas, Dorothea; Higuchi, Keiichi; Sawashita, Jinko; Mori, Masayuki; Döring, Frank (2010). "The reduced form of coenzyme Q10 mediates distinct effects on cholesterol metabolism at the transcriptional and metabolite level in SAMP1 mice". IUBMB Life 62 (11): 812–8. doi:10.1002/iub.388. PMID 21086475. 
  10. ^ Zlatohlavek, L; Vrablik, M; Grauova, B; Motykova, E; Ceska, R (2012). "The effect of coenzyme Q10 in statin myopathy". Neuro endocrinology letters. 33 Suppl 2: 98–101. PMID 23183519. 
  11. ^ Vaughan, Roger A.; Garcia-Smith, Randi; Bisoffi, Marco; Conn, Carole A.; Trujillo, Kristina A. (2013). "Ubiquinol rescues simvastatin-suppression of mitochondrial content, function and metabolism: Implications for statin-induced rhabdomyolysis". European Journal of Pharmacology 711 (1–3): 1–9. doi:10.1016/j.ejphar.2013.04.009. PMID 23624330. 
  12. ^ a b c Žáková, Pavla; Kanďár, Roman; Škarydová, Lucie; Skalický, Jiří; Myjavec, Andrej; Vojtíšek, Petr (2007). "Ubiquinol-10/lipids ratios in consecutive patients with different angiographic findings". Clinica Chimica Acta 380 (1–2): 133–8. doi:10.1016/j.cca.2007.01.025. PMID 17336955. 
  13. ^ Lim, S. C.; Tan, H. H.; Goh, S. K.; Subramaniam, T.; Sum, C. F.; Tan, I. K.; Lee, B. L.; Ong, C. N. (2006). "Oxidative burden in prediabetic and diabetic individuals: Evidence from plasma coenzyme Q10". Diabetic Medicine 23 (12): 1344–9. doi:10.1111/j.1464-5491.2006.01996.x. PMID 17116186. 
  14. ^ Yamamoto, Yorihiro; Yamashita, Satoshi (1999). "Plasma ubiquinone to ubiquinol ratio in patients with hepatitis, cirrhosis, and hepatoma, and in patients treated with percutaneous transluminal coronary reperfusion". BioFactors 9 (2–4): 241–6. doi:10.1002/biof.5520090219. PMID 10416036. 
  15. ^ Wada, Hiroo; Goto, Hajime; Hagiwara, Shin-Ichi; Yamamoto, Yorihiro (2007). "Redox Status of Coenzyme Q10 is Associated with Chronological Age". Journal of the American Geriatrics Society 55 (7): 1141–2. doi:10.1111/j.1532-5415.2007.01209.x. PMID 17608895. 
  16. ^ Fiorini, Rosamaria; Ragni, Letizia; Ambrosi, Simona; Littarru, Gian Paolo; Gratton, Enrico; Hazlett, Theodore (2007). "Fluorescence Studies of the Interactions of Ubiquinol-10 with Liposomes". Photochemistry and Photobiology 84 (1): 209–14. doi:10.1111/j.1751-1097.2007.00221.x. PMID 18173722. 
  17. ^ Shimizu, K, et al. (November 6 and 7, 2010). "Collaborative research with Waseda University and Tsukuba University". The 21st Annual Meeting of Japanese Society of Clinical Sports Medicine. Tsukuba International Congress Center, Tsukuba, Ibraki Prefecture, Japan. 
  18. ^ Onur, S; Niklowitz, P; Jacobs, G; Nöthlings, U; Lieb, W; Menke, T; Döring, F (2014). "Ubiquinol reduces gamma glutamyltransferase as a marker of oxidative stress in humans". BMC research notes 7 (1): 427. doi:10.1186/1756-0500-7-427. PMC 4105833. PMID 24996614.  edit
  19. ^ Shults, C. W.; Oakes, D; Kieburtz, K; Beal, MF; Haas, R; Plumb, S; Juncos, JL; Nutt, J et al. (2002). "Effects of Coenzyme Q10 in Early Parkinson Disease: Evidence of Slowing of the Functional Decline". Archives of Neurology 59 (10): 1541–50. doi:10.1001/archneur.59.10.1541. PMID 12374491. 
  20. ^ Parkinson Study Group QE3 Investigators. Beal MF, Oakes D, Shoulson I, Henchcliffe C, Galpern WR et al. (2014). "A randomized clinical trial of high-dosage coenzyme q10 in early Parkinson disease: no evidence of benefit.". JAMA Neurol 71 (5): 543–52. doi:10.1001/jamaneurol.2014.131. PMID 24664227. 
  21. ^ Sugano, N, et al. (June 4 and 5, 2011). "Research by Nihon University School of Dentistry". The Sixty-third Meeting of the Vitamin Society of Japan. Hiroshima, Japan. 
  22. ^ Ryo, Koufuchi; Ito, Atsuko; Takatori, Rie; Tai, Yoshinori; Arikawa, Kazumune; Seido, Taro; Yamada, Takashi; Shinpo, Keiko et al. (2011). "Effects of coenzyme Q10 on salivary secretion". Clinical Biochemistry 44 (8–9): 669–74. doi:10.1016/j.clinbiochem.2011.03.029. PMID 21406193. 
  23. ^ Ishikawa, Akira; Kawarazaki, Hiroo; Ando, Katsuyuki; Fujita, Megumi; Fujita, Toshiro; Homma, Yukio (2010). "Renal preservation effect of ubiquinol, the reduced form of coenzyme Q10". Clinical and Experimental Nephrology 15 (1): 30–3. doi:10.1007/s10157-010-0350-8. PMID 20878200. 
  24. ^ Safarinejad, Mohammad Reza; Safarinejad, Shiva; Shafiei, Nayyer; Safarinejad, Saba (2012). "Effects of the Reduced Form of Coenzyme Q10 (Ubiquinol) on Semen Parameters in Men with Idiopathic Infertility: A Double-Blind, Placebo Controlled, Randomized Study". The Journal of Urology 188 (2): 526–31. doi:10.1016/j.juro.2012.03.131. 
  25. ^ Döring, Frank; Schmelzer, Constance; Lindner, Inka; Vock, Christina; Fujii, Kenji (2007). "Functional connections and pathways of coenzyme Q10-inducible genes: An in-silico study". IUBMB Life 59 (10): 628–633. doi:10.1080/15216540701545991. PMID 17852568. 
  26. ^ Schmelzer, Constance; Kubo, Hiroshi; Mori, Masayuki; Sawashita, Jinko; Kitano, Mitsuaki; Hosoe, Kazunori; Boomgaarden, Inka; Döring, Frank; Higuchi, Keiichi (2009). "Supplementation with the reduced form of Coenzyme Q10 decelerates phenotypic characteristics of senescence and induces a peroxisome proliferator-activated receptor-α gene expression signature in SAMP1 mice". Molecular Nutrition & Food Research 54 (6): 805. doi:10.1002/mnfr.200900155. 
  27. ^ James, Andrew M.; Cochemé, Helena M.; Smith, Robin A. J.; Murphy, Michael P. (2005). "Interactions of Mitochondria-targeted and Untargeted Ubiquinones with the Mitochondrial Respiratory Chain and Reactive Oxygen Species: Implications for the use of exogenous ubiquinones as therapies and experimental tools". Journal of Biological Chemistry 280 (22): 21295–312. doi:10.1074/jbc.M501527200. PMID 15788391. 
  28. ^ Hosoe, Kazunori; Kitano, Mitsuaki; Kishida, Hideyuki; Kubo, Hiroshi; Fujii, Kenji; Kitahara, Mikio (2007). "Study on safety and bioavailability of ubiquinol (Kaneka QH™) after single and 4-week multiple oral administration to healthy volunteers". Regulatory Toxicology and Pharmacology 47 (1): 19–28. doi:10.1016/j.yrtph.2006.07.001. PMID 16919858. 
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  30. ^ Kubo, Hiroshi; Fujii, Kenji; Kawabe, Taizo; Matsumoto, Shuka; Kishida, Hideyuki; Hosoe, Kazunori (2008). "Food content of ubiquinol-10 and ubiquinone-10 in the Japanese diet". Journal of Food Composition and Analysis 21 (3): 199–210. doi:10.1016/j.jfca.2007.10.003. 
  31. ^ Slater, E.C. (1983). "The Q cycle, an ubiquitous mechanism of electron transfer". Trends in Biochemical Sciences 8 (7): 239–42. doi:10.1016/0968-0004(83)90348-1. 
  32. ^ Trumpower BL (June 1990). "Cytochrome bc1 complexes of microorganisms". Microbiol. Rev. 54 (2): 101–29. PMC 372766. PMID 2163487. 
  33. ^ Trumpower, Bernard L. (1990). "The Protonmotive Q Cycle". The Journal of Biological Chemistry 265 (20): 11409–12. PMID 2164001. 
  34. ^ http://proteopedia.org/wiki/index.php/Complex_III_of_Electron_Transport_Chain[full citation needed][unreliable medical source?]

External links[edit]