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Coenzyme Q10



  Coenzyme Q10 (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10, CoQ, Q10, or Q) is a benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the isoprenyl chemical subunits.

This vitamin-like substance is, by nature, present in all human cells and responsible for the production of the body’s own energy. In each human cell, food energy is converted into energy in the mitochondria with the aid of CoQ10. Ninety-five percent of all the human body’s energy requirements (ATP) is converted with the aid of CoQ10.[1][2] Therefore, those organs with the highest energy requirements – such as the heart, the lungs, and the liver – have the highest CoQ10 concentrations.[3][4][5]

Additional recommended knowledge

Contents

History

Coenzyme Q was first discovered by professor Fred L. Crane and colleagues at the University of Wisconsin-Madison Enzyme Institute in 1957.[6][7] In 1958, its chemical structure was reported by Professor Karl Folkers and coworkers at Merck.[8][7] For his discovery of the significant part played by CoQ10 in energy production, the British scientist Peter D. Mitchell was awarded the Nobel Prize for chemistry in 1978.

Chemical properties

The oxidized structure of CoQ, or Q, is given here. The various kinds of Coenzyme Q can be distinguished by the number of isoprenoid side-chains they have. The most common CoQ in human mitochondria is Q10. The image to the right has three isoprenoid units and would be called Q3.
If Coenzyme Q is reduced by one equivalent, the following structure results, a ubisemiquinone, and is denoted QH. Note the free-radical on one of the ring oxygens (either oxygen may become a free-radical, in this case the top oxygen is shown as such).
If Coenzyme Q is reduced by two equivalents, the compound becomes a ubiquinol, denoted QH2:

Biochemical role

  CoQ is found in the membranes of endoplasmic reticulum, peroxisomes, lysosomes, vesicles, and the inner membrane of the mitochondrion, where it is an important part of the electron transport chain; there it passes reducing equivalents to acceptors such as Coenzyme Q: cytochrome c - oxidoreductase:

CoQH2+ 2 FeIII-cytochrome c → CoQ + 2 FeII-cytochrome c

CoQ is also essential in the formation of the apoptosome, along with other adapter proteins. The loss of trophic factors activates pro-apoptotic enzymes, causing the breakdown of mitochondria.

Antioxidant role of CoQ10 in the body

Apart from being a cofactor in the mitochondrial electron transport chain, CoQ10 in its reduced form (ubiquinol or CoQ10 H2) serves as an important antioxidant in both mitochondria and lipid membranes, where it protects the body's cells in their battle against the destructive effects of free-radicals. In human LDL, it affords protection against the oxidative modifications of LDL themselves, thus lowering their atherogenic potency.[9] CoQ10 is essential in vitamin E regeneration. Ubiquinol inhibits protein and lipid oxidation in cell membranes, and helps to minimize oxidative injury to DNA.[10] CoQ10 is an integral part of the respiratory chain and thereby located exactly where the free-radicals are generated, in the mitochondria. These endogeneously-produced free-radicals are considered an import factor of the aging process.[11]

Supplementation

Because of its ability to transfer electrons and therefore act as an antioxidant, Coenzyme Q is also used as a dietary supplement. Young people are able to make Q10 from the lower-numbered ubiquinones such as Q6 or Q8.[citation needed] The sick and elderly may not be able to make enough, thus Q10 becomes a vitamin later in life and in illness.[citation needed]

Mitochondrial disorders

Supplementation of Coenzyme Q10 is a treatment for some of the very rare and serious mitochondrial disorders and other metabolic disorders, where patients are not capable of producing enough coenzyme Q10 because of their disorder. Coenzyme Q10 is then prescribed by a physician.[12]

Migraine headaches

Supplementation of Coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraine headaches. So far, three studies have been done, of which two were small, did not have a placebo group, were not randomized, and were open-label,[13] and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.[14] Dosages were 150 to 300 mg/day.

Cancer

It is also being investigated as a treatment for cancer, and as relief from cancer treatment side-effects.[15]

Brain health and neurodegenerative diseases

Recent studies have shown that the antioxidant properties of Coenzyme Q10 benefit the body and the brain in animal models.[16] Some of these studies indicate that Coenzyme Q10 protects the brain from neurodegenerative disease such as Parkinson's,[17] although it does not relieve the symptoms.[18] Dosage was 300 mg per day.

Cardiac arrest

Another recent study shows a survival benefit after cardiac arrest if coenzyme Q10 is administered in addition to commencing active cooling (to 32–34 degrees Celsius).[19]

Blood pressure

There are several reports concerning the effect of CoQ10 on blood pressure in human studies.[20] In a recent meta-analysis of the clinical trials of CoQ10 for hypertension, a research group led by Professor FL Rosenfeldt (from the Cardiac Surgical Research Unit, Alfred Hospital, Melbourne, Australia) reviewed all published trials of Coenzyme Q10 for hypertension, and assessed overall efficacy, consistency of therapeutic action, and side-effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study, and eight open-label studies. The research group concluded that coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side-effects.[21]

Biosynthesis

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 used for the first steps of cholesterol biosynthesis.

Inhibition by statins and beta blockers

Coenzyme Q10 shares a common biosynthetic pathway with cholesterol. The synthesis of an intermediary precursor of Coenzyme Q10, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication,[22] and statins, a class of cholesterol-lowering drugs.[23] Statins can reduce serum levels of coenzyme Q10 by up to 40%.[24] Some research suggests the logical option of supplementation with coenzyme Q10 as a routine adjunct to any treatment that may reduce endogenous production of coenzyme Q10, based on a balance of likely benefit against very small risk.[25][26]

Occurrence in nature

CoQ10 occurs in mackerel and herring fresh heart tissue in concentrations of 105-148 μg/g. In fresh mackerel "red and white tissue," CoQ10 concentrations of 67 and 15 μg/g, respectively, have been reported. In fresh herring tissue, an amount of 15–24 μg/g of CoQ10 has been reported.[27]

CoQ10 Content of various foods:[28]

Food CoQ10
[μg/g]
Portion of Food
[g]
CoQ10 Amount in Portion
[mg]
Pork heart 203 120 24
Chicken leg 17 120 2.0
Beef heart 41 120 4.8

References

  1. ^ Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271: 195-204, 1995
  2. ^ Dutton PL, Ohnishi T, Darrouzet E, Leonard, MA, Sharp RE, Cibney BR, Daldal F and Moser CC. 4 Coenzyme Q oxidation reduction reactions in mitochondrial electron transport (pp 65-82) in Coenzyme Q: Molecular mechanisms in health and disease edited by Kagan VE and Quinn PJ, CRC Press (2000), Boca Raton
  3. ^ Okamoto, T.et al (1989) Interna.J.Vit.Nutr.Res.,59,288-292
  4. ^ Aberg,F.et al (1992)Archives of Biochemistry and Biophysics, 295, 230-234
  5. ^ Shindo, Y., Witt, E., Han, D., Epstein, W., and Packer, L., Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin, Invest. Dermatol., 102 (1994) 122-124.
  6. ^ Crane F, Hatefi Y, Lester R, Widmer C (1957). "Isolation of a quinone from beef heart mitochondria". Biochim Biophys Acta 25 (1): 220-1. PMID 13445756.
  7. ^ a b Peter H. Langsjoen, "Introduction of Coezyme Q10"
  8. ^ Wolf DE, Hoffman CH, Trenner NR, Arison BH, Shunk CH, Linn BD, McPherson JF, and Folkers K. Structure studies on the coenzyme Q group. J Am Chem Soc 1958: 80:4752.
  9. ^ Alleva R, Tomasetti M, Battino M, Curatola G, Littarru GP, Folkers K: The roles of coenzyme Q10 and vitamin E on peroxidation of human low density subfractions. Proc Nat Acad Sci. USA, 92: 9388-9391, 1995
  10. ^ Tomasetti M., Littarru G.P., Stocker R., Alleva R.: Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes. Free Radic Biol Med. 27: 1027-1032, 1999
  11. ^ Lenaz G, Bovina C, D'Aurelio M, Fato R, Formiggini G, Genova ML, Giuliano G, Pich MM, Paolucci U, Castelli GP, Ventura B: Role of mitochondria in oxidative stress and aging. Ann N Y Acad Sci 959:199-213, 2002
  12. ^ Berbel-Garcia, A.; et al. (July 2004). "Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS". Clinical Neuropharmacology 27: 187-191. PMID 15319706. Retrieved on 2006-12-01.
  13. ^ Rozen T, Oshinsky M, Gebeline C, Bradley K, Young W, Shechter A, Silberstein S (2002). "Open label trial of coenzyme Q10 as a migraine preventive". Cephalalgia 22 (2): 137-41. PMID 11972582.
  14. ^ Sándor PS, et al. (2005). "Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial". Neurology 64: 713-715.
  15. ^ Katsuhisa Sakano, Mami Takahashi, Mitsuaki Kitano, Takashi Sugimura, Keiji Wakabayashi: Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats. Asian Pacific J Cancer Prev, 7, 599-603, 2006
  16. ^ Matthews, R. T.; et al. (July 1998). "Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects". PNAS 95: 8892-8897. Retrieved on 2006-12-01.
  17. ^ Biol Signals Recept. 2001 May-Aug;10(3-4):224-53
  18. ^ Alexander Storch, MD; Wolfgang H. Jost, MD; Peter Vieregge, MD; Jörg Spiegel, MD; Wolfgang Greulich, MD; Joachim Durner, MD; Thomas Müller, MD; Andreas Kupsch, MD; Henning Henningsen, MD; Wolfgang H. Oertel, MD; Gerd Fuchs, MD; Wilfried Kuhn, MD; Petra Niklowitz, MD; Rainer Koch, PhD; Birgit Herting, MD; Heinz Reichmann, MD; for the German Coenzyme Q10 Study Group (May 14, 2007). Randomized, Double-blind, Placebo-Controlled Trial on Symptomatic Effects of Coenzyme Q10 in Parkinson Disease. Archives of Neurologu.
  19. ^ Damian, M. S.; et al. (July 2004). "Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest". Circulation, American Heart Foundation 110: 3011-3016. Retrieved on 2006-12-01.
  20. ^ Cupp MJ and Tracy TS. Chapter 4: Coenzyme Q10 (Ubiquinone, Ubidecarenone), pp 53-85 in Dietary Supplements edited by Cupp MJ and Tracy TS Humana press, Totowa, New Jersey (2003)
  21. ^ Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong J-Y, Watts GF. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Human Hypertension 21: 297-306, 2007
  22. ^ Kishi T, Watanabe T, Folkers K (1977). "Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors". Res Commun Chem Pathol Pharmacol 17 (1): 157-64. PMID 17892.
  23. ^ http://www.cholesterol-and-health.com/Synthesis-Of-Cholesterol.html
  24. ^ Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco A, Littarru G (1993). "Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study". J Clin Pharmacol 33 (3): 226-9. PMID 8463436.
  25. ^ Sarter B (2002). "Coenzyme Q10 and cardiovascular disease: a review". J Cardiovasc Nurs 16 (4): 9-20. PMID 12597259.
  26. ^ Thibault A, Samid D, Tompkins A, Figg W, Cooper M, Hohl R, Trepel J, Liang B, Patronas N, Venzon D, Reed E, Myers C (1996). "Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer". Clin Cancer Res 2 (3): 483-91. PMID 9816194.
  27. ^ Nathalie Soucheta and Serge Laplante, Seasonal variation of Co-enzyme Q10 content in pelagic fish tissues from Eastern Quebec
  28. ^ www.thefactsaboutfitness.com
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Coenzyme_Q10". A list of authors is available in Wikipedia.
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