Ubiquinone, ubidecarenone, coenzyme Q, CoQ10 //, CoQ, Q10
3D model (JSmol)
CompTox Dashboard (EPA)
|Molar mass||863.365 g·mol−1|
|Appearance||yellow or orange solid|
|Melting point||48–52 °C (118–126 °F; 321–325 K)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
Coenzyme Q, also known as ubiquinone, is a coenzyme family that is ubiquitous in animals and most bacteria (hence the name ubiquinone). In humans, the most common form is Coenzyme Q10 or ubiquinone-10. CoQ10 is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of any medical condition. It, however, is sold as a dietary supplement.
It is a 1,4-benzoquinone, where Q refers to the quinone chemical group and 10 refers to the number of isoprenyl chemical subunits in its tail. In natural ubiquinones, the number can be anywhere from 6 to 10; this family of fat-soluble substances, which resembles a vitamin, is present in all respiring eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, which generates energy in the form of ATP. Ninety-five percent of the human body's energy is generated this way. Therefore, those organs with the highest energy requirements—such as the heart, liver, and kidney—have the highest CoQ10 concentrations.
There are three redox states of CoQ: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol). The capacity of this molecule to act as a two-electron carrier (moving between the quinone and quinol form) and a one-electron carrier (moving between the semiquinone and one of these other forms) is central to its role in the electron transport chain due to the iron–sulfur clusters that can only accept one electron at a time, and as a free-radical–scavenging antioxidant.
- 1 Deficiency and toxicity
- 2 Supplementation
- 3 Interactions
- 4 Chemical properties
- 5 Biosynthesis
- 6 Absorption and metabolism
- 7 Pharmacokinetics
- 8 History
- 9 Dietary concentrations
- 10 See also
- 11 References
- 12 External links
Deficiency and toxicity
There are two major factors that lead to deficiency of CoQ10 in humans: reduced biosynthesis, and increased use by the body. Biosynthesis is the major source of CoQ10. Biosynthesis requires at least 12 genes, and mutations in many of them cause CoQ deficiency. CoQ10 levels also may be affected by other genetic defects (such as mutations of mitochondrial DNA, ETFDH, APTX, FXN, and BRAF, genes that are not directly related to the CoQ10 biosynthetic process). The role of statins in deficiencies is controversial.[needs update]
Some adverse effects, largely gastrointestinal, are reported with very high intakes; the observed safe level (OSL) risk assessment method indicated that the evidence of safety is strong at intakes up to 1200 mg/day, and this level is identified as the OSL.
Although CoQ10 may be measured in blood plasma, these measurements reflect dietary intake rather than tissue status. Currently, most clinical centers measure CoQ10 levels in cultured skin fibroblasts, muscle biopsies, and blood mononuclear cells. Culture fibroblasts can be used also to evaluate the rate of endogenous CoQ10 biosynthesis, by measuring the uptake of 14C-labelled p-hydroxybenzoate.
CoQ10 is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of any medical condition, it is sold as a dietary supplement. In the U.S., supplements are not regulated as drugs, but as foods. How CoQ10 is manufactured is not regulated and different batches and brands may vary significantly.
A 2004 laboratory analysis by ConsumerLab.com of CoQ10 supplements on the market found that some did not contain the quantity identified on the product label. Amounts varied from "no detectable CoQ10", to 75% of stated dose, and up to a 75% excess.
While there is no established ideal dosage of CoQ10, a typical daily dose is 100–200 milligrams. Different brands may have varying ingredients and strengths.
One 2014 Cochrane review found "no convincing evidence to support or refute" the use of CoQ10 for the treatment of heart failure. Another 2014 Cochrane review found insufficient evidence to make a conclusion about its use for the prevention of heart disease. A 2016 Cochrane review concluded that CoQ10 had no effects on blood pressure. In a 2017 meta-analysis only a tiny decrease in mortality was noted in people with heart failure receiving CoQ10.
CoQ10 has been routinely used to treat muscle breakdown associated as a side effect of use of statin medications. A 2015 meta-analysis of randomized controlled trials found that CoQ10 had no effect on statin myopathy. A 2018 meta-analysis concluded that there was preliminary evidence for oral CoQ10 reducing statin-associated muscle symptoms, including muscle pain, muscle weakness, muscle cramps and muscle tiredness.
No large well-designed clinical trials of CoQ10 in cancer treatment have been conducted. The US' National Cancer Institute identified issues with the few, small studies that have been done stating, "the way the studies were done and the amount of information reported made it unclear if benefits were caused by the CoQ10 or by something else". The American Cancer Society has concluded, "CoQ10 may reduce the effectiveness of chemo and radiation therapy, so most oncologists would recommend avoiding it during cancer treatment."
A 1995 review study found that there is no clinical benefit to the use of CoQ10 in the treatment of periodontal disease. Most of the studies suggesting otherwise were outdated, focused on in vitro tests, had too few test subjects and/or erroneous statistical methodology and trial setup, or were sponsored by a manufacturer of the product.
Coenzyme Q10 has potential to inhibit the effects of warfarin (Coumadin), a potent anticoagulant, by reducing the INR, a measure of blood clotting. The structure of coenzyme Q10 is very much similar to the structure of vitamin K, which competes with and counteracts warfarin's anticoagulation effects. Coenzyme Q10 should be avoided in patients currently taking warfarin due to the increased risk of clotting.
The oxidized structure of CoQ10 is shown on the top-right. The various kinds of Coenzyme Q may be distinguished by the number of isoprenoid subunits in their side-chains; the most common Coenzyme Q in human mitochondria is CoQ10. Q refers to the quinone head and 10 refers to the number of isoprene repeats in the tail; the molecule below has three isoprenoid units and would be called Q3.
Biosynthesis occurs in most human tissue. There are three major steps:
- Creation of the benzoquinone structure (using phenylalanine or tyrosine, via 4-hydroxybenzoate)
- Creation of the isoprene side chain (using acetyl-CoA)
- The joining or condensation of the above two structures
An important enzyme in this pathway is HMG-CoA reductase, usually a target for intervention in cardiovascular complications; the "statin" family of cholesterol-reducing medications inhibits HMG-CoA reductase. One possible side effect of statins is decreased production of CoQ10, which may be connected to the development of myopathy and rhabdomyolysis. However, the role statin plays in CoQ deficiency is controversial. Although these drug reduce blood levels of CoQ, studies on the effects of muscle levels of CoQ are yet to come. CoQ supplementation also does not reduce side effects of statin.
Organisms other than human use somewhat different source chemicals to produce the benzoquinone structure and the isoprene structure. For example, the bacteria E. coli produces the former from chorismate and the latter from a non-mevalonate source. The common yeast S. cerevisiae, however, derives the former from either chorismate or tyrosine and the latter from mevalonate. Most organisms share the common 4-hydroxybenzoate intermediate, yet again uses different steps to arrive at the "Q" structure.
Absorption and metabolism
CoQ10 is a crystalline powder insoluble in water. Absorption follows the same process as that of lipids; the uptake mechanism appears to be similar to that of vitamin E, another lipid-soluble nutrient; this process in the human body involves secretion into the small intestine of pancreatic enzymes and bile, which facilitates emulsification and micelle formation required for absorption of lipophilic substances. Food intake (and the presence of lipids) stimulates bodily biliary excretion of bile acids and greatly enhances absorption of CoQ10. Exogenous CoQ10 is absorbed from the small intestine and is best absorbed if taken with a meal. Serum concentration of CoQ10 in fed condition is higher than in fasting conditions.
Data on the metabolism of CoQ10 in animals and humans are limited. A study with 14C-labeled CoQ10 in rats showed most of the radioactivity in the liver two hours after oral administration when the peak plasma radioactivity was observed, but CoQ9 (with only 9 isoprenyl units) is the predominant form of coenzyme Q in rats. It appears that CoQ10 is metabolised in all tissues, while a major route for its elimination is biliary and fecal excretion. After the withdrawal of CoQ10 supplementation, the levels return to normal within a few days, irrespective of the type of formulation used.
Some reports have been published on the pharmacokinetics of CoQ10. The plasma peak can be observed 2–6 hours after oral administration, depending mainly on the design of the study. In some studies, a second plasma peak also was observed at approximately 24 hours after administration, probably due to both enterohepatic recycling and redistribution from the liver to circulation. Tomono et al. used deuterium-labeled crystalline CoQ10 to investigate pharmacokinetics in humans and determined an elimination half-time of 33 hours.
Improving the bioavailability of CoQ10
The importance of how drugs are formulated for bioavailability is well known. In order to find a principle to boost the bioavailability of CoQ10 after oral administration, several new approaches have been taken; different formulations and forms have been developed and tested on animals and humans.
Reduction of particle size
Nanoparticles have been explored as a delivery system for various drugs, such as improving the oral bioavailability of drugs with poor absorption characteristics. However, this protocol has not proved successful with CoQ10, although reports have differed widely. The use of aqueous suspension of finely powdered CoQ10 in pure water also reveals only a minor effect.
Soft-gel capsules with CoQ10 in oil suspension
A successful approach was to use the emulsion system to facilitate absorption from the gastrointestinal tract and to improve bioavailability. Emulsions of soybean oil (lipid microspheres) could be stabilised very effectively by lecithin and were used in the preparation of soft gelatin capsules. In one of the first such attempts, Ozawa et al. performed a pharmacokinetic study on beagles in which the emulsion of CoQ10 in soybean oil was investigated; about twice the plasma CoQ10 level than that of the control tablet preparation was determined during administration of a lipid microsphere. Although an almost negligible improvement of bioavailability was observed by Kommuru et al. with oil-based softgel capsules in a later study on dogs, the significantly increased bioavailability of CoQ10 was confirmed for several oil-based formulations in most other studies.
Novel forms of CoQ10 with increased water-solubility
Facilitating drug absorption by increasing its solubility in water is a common pharmaceutical strategy and also has been shown to be successful for CoQ10. Various approaches have been developed to achieve this goal, with many of them producing significantly better results over oil-based softgel capsules in spite of the many attempts to optimize their composition. Examples of such approaches are use of the aqueous dispersion of solid CoQ10 with the polymer tyloxapol, formulations based on various solubilising agents, such as hydrogenated lecithin, and complexation with cyclodextrins; among the latter, the complex with β-cyclodextrin has been found to have highly increased bioavailability. and also is used in pharmaceutical and food industries for CoQ10-fortification.
In 1950, G. N. Festenstein was the first to isolate a small amount of CoQ10 from the lining of a horse's gut at Liverpool, England. In subsequent studies the compound was briefly called substance SA, it was deemed to be quinone and it was noted that it could found from many tissues of a number of animals.
In 1957, Frederick L. Crane and colleagues at the University of Wisconsin–Madison Enzyme Institute isolated the same compound from mitochondrial membranes of beef heart and noted that it transported electrons within mitochondria. They called it Q-275 for short as it was a quinone. Soon they noted that Q-275 and substance SA studied in England may be the same compound; this was confirmed later that year and Q-275/substance SA was renamed ubiquinone as it was an ubiquitous quinone that could be found from all animal tissues.
In 1958, its full chemical structure was reported by D. E. Wolf and colleagues working under Karl Folkers at Merck in Rahway. Later that year D. E. Green and colleagues belonging to the Wisconsin research group suggested that ubiquinone should be called either mitoquinone or coenzyme Q due to its participation to the mitochondrial electron transport chain.
In 1960s Peter D. Mitchell enlarged upon the understanding of mitochondrial function via his theory of electrochemical gradient, which involves CoQ10, and in late 1970s studies of Lars Ernster enlargened upon the importance of CoQ10 as an antioxidant. The 1980s witnessed a steep rise in the number of clinical trials involving CoQ10.
Detailed reviews on occurrence of CoQ10 and dietary intake were published in 2010. Besides the endogenous synthesis within organisms, CoQ10 also is supplied to the organism by various foods. Despite the scientific community's great interest in this compound, however, a very limited number of studies have been performed to determine the contents of CoQ10 in dietary components. The first reports on this aspect were published in 1959, but the sensitivity and selectivity of the analytical methods at that time did not allow reliable analyses, especially for products with low concentrations. Since then, developments in analytical chemistry have enabled a more reliable determination of CoQ10 concentrations in various foods:
CoQ10 levels in selected foods Food CoQ10 concentration (mg/kg) Beef heart 113 liver 39–50 muscle 26–40 Pork heart 12–128 liver 23–54 muscle 14–45 Chicken breast 8–17 thigh 24–25 wing 11 Fish sardine 5–64 mackerel: – red flesh 43–67 – white flesh 11–16 salmon 4–8 tuna 5 Oils soybean 54–280 olive 4–160 grapeseed 64–73 sunflower 4–15 canola 64–73 Nuts peanut 27 walnut 19 sesame seed 18–23 pistachio 20 hazelnut 17 almond 5–14 Vegetables parsley 8–26 broccoli 6–9 cauliflower 2–7 spinach up to 10 Chinese cabbage 2–5 Fruit avocado 10 blackcurrant 3 grape 6–7 strawberry 1 orange 1–2 grapefruit 1 apple 1 banana 1
Meat and fish are the richest sources of dietary CoQ10; levels over 50 mg/kg may be found in beef, pork, chicken heart, and chicken liver. Dairy products are much poorer sources of CoQ10 compared to animal tissues. Vegetable oils also are quite rich in CoQ10. Within vegetables, parsley and perilla are the richest CoQ10 sources, but significant differences in their CoQ10 levels may be found in the literature. Broccoli, grapes, and cauliflower are modest sources of CoQ10. Most fruit and berries represent a poor to very poor source of CoQ10, with the exception of avocados, which have a relatively high CoQ10 content.
In the developed world, the estimated daily intake of CoQ10 has been determined at 3–6 mg per day, derived primarily from meat.
Effect of heat and processing
Cooking by frying reduces CoQ10 content by 14–32%.
- Idebenone – synthetic analog with reduced oxidant generating properties
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