 | |
| Names | |
|---|---|
| Preferred IUPAC name 2-[(2E,6E,10E,14E,18E,22E,26E,30E,34E)-3,7,11,15,19,23,27,31,35,39-Decamethyltetraconta-2,6,10,14,18,22,26,30,34,38-decaen-1-yl]-5,6-dimethoxy-3-methylcyclohexa-2,5-diene-1,4-dione | |
Other names
Q10, CoQ10/ˌkoʊˌkjuːˈtɛn/ | |
| Identifiers | |
| |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
|
| ECHA InfoCard | 100.005.590 |
| KEGG | |
| UNII | |
| |
| |
| Properties | |
| C59H90O4 | |
| Molar mass | 863.365 g·mol−1 |
| Appearance | yellow or orange solid |
| Melting point | 48–52 °C (118–126 °F; 321–325 K) |
| insoluble | |
| Pharmacology | |
| C01EB09 (WHO) | |
| Related compounds | |
Relatedquinones | 1,4-Benzoquinone Plastoquinone Ubiquinol |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Coenzyme Q10 (CoQ10/ˌkoʊkjuːˈtɛn/), also known asubiquinone, is a naturally occurringbiochemical cofactor (coenzyme) and anantioxidant produced by the human body.[1][2][3] It can also be obtained from dietary sources, such as meat, fish, seed oils, vegetables, anddietary supplements.[1][2] CoQ10 is found in many organisms, including animals and bacteria.
CoQ10 plays a role inmitochondrialoxidative phosphorylation, aiding in the production ofadenosine triphosphate (ATP), which is involved in energy transfer within cells.[1] The structure of CoQ10 consists of a benzoquinone moiety and an isoprenoid side chain, with the "10" referring to the number ofisoprenyl chemical subunits in its tail.[4][5][6]
Although a ubiquitous molecule in human tissues, CoQ10 is not a dietarynutrient and does not have arecommended intake level, and its use as a supplement is notapproved in the United States for any health or anti-disease effect.[1][2]
CoQ10 is a component of the mitochondrialelectron transport chain (ETC), where it plays a role in oxidative phosphorylation, a process required for the biosynthesis of adenosine triphosphate, the primary energy source of cells.[1][6][7]
CoQ10 is alipophilic molecule that is located in all biological membranes of human body and serves as a component for the synthesis of ATP and is a life-sustaining cofactor for the three complexes (complex I,complex II, andcomplex III) of the ETC in the mitochondria.[1][5] CoQ10 has a role in the transport ofprotons acrosslysosomal membranes to regulate pH in lysosome functions.[1]
The mitochondrial oxidative phosphorylation process occurs in the inner mitochondrial membrane of eukaryotic cells.[1] This membrane is highly folded into structures called cristae, which increase the surface area available for oxidative phosphorylation. CoQ10 plays a role in this process as an essential cofactor of the ETC located in the inner mitochondrial membrane and serves the following functions:[1][7]
 | This articleneeds attention from an expert in biochemistry. See thetalk page for details.WikiProject Biochemistry may be able to help recruit an expert.(April 2024) |
Coenzymes Q is acoenzyme family that isubiquitous in animals and manyPseudomonadota,[10] a group of gram-negative bacteria. The fact that the coenzyme is ubiquitous gives the origin of its other name, ubiquinone.[1][2][11] In humans, the most common form of coenzymes Q is coenzyme Q10, also called CoQ10 (/ˌkoʊkjuːˈtɛn/) or ubiquinone-10.[1]
Coenzyme Q10 is a1,4-benzoquinone, in which "Q" refers to thequinone chemical group and "10" refers to the number ofisoprenyl chemical subunits (shown enclosed in brackets in the diagram) in its tail.[1] In natural ubiquinones, there are from six to ten subunits in the tail, with humans having a tail of 10 isoprene units (50 carbon atoms) connected to its benzoquinone "head".[1]
This family of fat-soluble substances is present in all respiringeukaryotic cells, primarily in the mitochondria.[1] Ninety-five percent of the human body's energy is generated this way.[12] Organs with the highest energy requirements—such as theheart,liver, andkidney—have the highest CoQ10 concentrations.[13][14][15][16]
There are threeredox states of CoQ: fully oxidized (ubiquinone),semiquinone (ubisemiquinone), and fullyreduced (ubiquinol).[1] 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 theiron–sulfur clusters that can only accept one electron at a time and as a free radical–scavenging antioxidant.[1][11]
There are two major pathways of deficiency of CoQ10 in humans: reducedbiosynthesis, and increased use by the body.[17] Biosynthesis is the major source of CoQ10. Biosynthesis requires at least 15genes, and mutations in any of them can cause CoQ deficiency.[17] CoQ10 levels also may be affected by other genetic defects (such as mutations ofmitochondrial DNA,ETFDH,APTX,FXN, andBRAF, genes that are not directly related to the CoQ10 biosynthetic process).[17] Some of these, such as mutations inCOQ6, can lead to serious diseases such as steroid-resistantnephrotic syndrome with sensorineuraldeafness.[18][19][20]
Although CoQ10 may be measured inblood plasma, these measurements reflect dietary intake rather than tissue status. Currently, most clinical centers measure CoQ10 levels in cultured skinfibroblasts, musclebiopsies, and blood mononuclear cells.[21] Culture fibroblasts can be used also to evaluate the rate of endogenous CoQ10 biosynthesis, by measuring the uptake of14C-labeledp-hydroxybenzoate.[22]
CoQ10 is studied as an adjunctive therapy to reduce inflammation inperiodontitis.[23]
Although statins may reduce CoQ10 in the blood it is unclear if they reduce CoQ10 in muscle.[24] Evidence does not support that supplementation improves statin side effects.[24][25]
The oxidized structure of CoQ10 is shown below. The various kinds of coenzyme Q may be distinguished by the number ofisoprenoid subunits in theirside-chains. The most common coenzyme Q in human mitochondria is CoQ10.[1] 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.
In its pure state, it is an orange-colored lipophile powder and has no taste or odor.[11]
Biosynthesis occurs in most human tissue. There are three major steps:
The initial two reactions occur inmitochondria, theendoplasmic reticulum, andperoxisomes, indicating multiple sites of synthesis in animal cells.[26]
An important enzyme in this pathway isHMG-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 ofmyopathy andrhabdomyolysis. However, the role statins play in CoQ deficiency is controversial. Although statins 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 medications.[21][24]
Genes involved includePDSS1,PDSS2,COQ2, andADCK3 (COQ8,CABC1).[27]
Organisms other than humans produce the benzoquinone and isoprene structures from somewhat different source chemicals. For example, the bacteriaE. coli produces the former fromchorismate and the latter from a non-mevalonate source. The common yeastS. cerevisiae, however, derives the former from either chorismate or tyrosine and the latter frommevalonate. Most organisms share the common 4-hydroxybenzoate intermediate, yet again uses different steps to arrive at the "Q" structure.[28]
Although neither aprescription drug nor anessential nutrient, CoQ10 is commonly used as a dietary supplement with the intent to prevent or improve disease conditions, such as cardiovascular disorders.[2][29] CoQ10 is naturally produced by the body and plays a crucial role in cell growth and protection.[6] Despite its significant role in the body, it is not used as a drug to treat any specific disease.[1][2][3]
Nevertheless, CoQ10 is widely available as an over-the-counter dietary supplement and is recommended by some healthcare professionals, despite a lack of definitive scientific evidence supporting these recommendations,[1][3] especially when it comes to cardiovascular diseases.[30]
CoQ10 is not approved by the U.S.Food and Drug Administration (FDA) for the treatment of any medical condition.[31][32][33][34] However, it is sold as adietary supplement not subject to the sameregulations as medicinal drugs, and is an ingredient in some cosmetics.[35] The manufacture of CoQ10 is not regulated, and different batches and brands may vary significantly.[33]
A 2014Cochrane review found insufficient evidence to make a conclusion about its use for the prevention of heart disease.[36] A 2016 Cochrane review concluded that CoQ10 had no effect onblood pressure.[37] A 2021 Cochrane review found "no convincing evidence to support or refute" the use of CoQ10 for the treatment of heart failure.[38]
A 2017meta-analysis of people with heart failure taking 30–100 mg/d of CoQ10 found a 31% lower mortality and increased exercise capacity, with no significant difference in the endpoints of left heart ejection fraction.[39] A 2021 meta-analysis found that coenzyme Q10 was associated with a 31% lower all-cause mortality in HF patients.[40] In a 2023 meta-analysis of older people, ubiquinone had evidence of a cardiovascular effect, but ubiquinol did not.[41]
Although CoQ10 has been studied as a potential remedy to treat purported muscle-relatedside effects ofstatin medications, the results were mixed. Although 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,[42] 2015[43] and 2024[30] meta-analysis found that CoQ10 had no effect on statin myopathy.[43][30]
CoQ10 is studied as an adjunctive therapy to reduce inflammation inperiodontitis.[23]
CoQ10 in the pure form is acrystalline powder insoluble in water. Absorption as a pharmacological substance follows the same process as that of lipids; the uptake mechanism appears to be similar to that ofvitamin E, another lipid-soluble nutrient.[16] This process in the human body involvessecretion into thesmall intestine ofpancreatic enzymes andbile, which facilitatesemulsification andmicelle formation required for absorption oflipophilic substances.[44] 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.[45][46]
CoQ10 is metabolized in all tissues, with the metabolites phosphorylated in cells.[2] CoQ10 is reduced to ubiquinol during or after absorption in thesmall intestine.[2] It is absorbed bychylomicrons, and redistributed in the blood withinlipoproteins.[2] Its elimination occurs viabiliary andfecalexcretion.[2]
Some reports have been published on thepharmacokinetics of CoQ10. The plasma peak can be observed 6–8 hours after oral administration when taken as a pharmacological substance.[2] In some studies, a second plasma peak was observed approximately 24 hours after administration, probably due to enterohepatic recycling and redistribution from the liver to circulation.[44]
Deuterium-labeled crystalline CoQ10 was used to investigate pharmacokinetics in humans to determine an elimination half-time of 33 hours.[47]
In contrast to the intake of CoQ10 as a constituent of food, such as nuts or meat, from which CoQ10 is normally absorbed, there is a concern about CoQ10 bioavailability when it is taken as a dietary supplement.[48][49] Bioavailability of CoQ10 supplements may be reduced due to the lipophilic nature of its molecule and large molecular weight.[48]
Nanoparticles have been explored as a delivery system for various drugs, such as improving the oral bioavailability of drugs with poor absorption characteristics.[50] However, this has not proved successful with CoQ10, although reports have differed widely.[51][52] The use of aqueoussuspension of finely powdered CoQ10 in pure water also reveals only a minor effect.[53]
Facilitating drug absorption by increasing its solubility in water is a common pharmaceutical strategy and also is successful for CoQ10. Various approaches have been developed to achieve this goal, with many of them producing significantly better results over oil-based soft gel capsules despite the many attempts to optimize their composition.[16] Examples of such approaches are use of the aqueous dispersion of solid CoQ10 with thepolymertyloxapol,[54] formulations based on various solubilising agents, such as hydrogenated lecithin,[55] andcomplexation withcyclodextrins; among the latter, the complex withβ-cyclodextrin has been found to have highly increased bioavailability[56][57] and also is used in pharmaceutical and food industries for CoQ10-fortification.[16]
Generally, oral CoQ10 supplementation is well tolerated.[1] The most common side effects are gastrointestinal symptoms (nausea, vomiting,appetite suppression, andabdominal pain),rashes, and headaches.[58] Some adverse effects, largely gastrointestinal, are reported with intakes.[2] Doses of 100–300 mg per day may induceinsomnia or elevateliver enzymes.[2] The observed safe level risk assessment method indicated that the evidence of safety is acceptable at intakes up to 1200 mg per day.[59]
Caution should be observed in the use of CoQ10 supplementation in people with bile duct obstruction and during pregnancy or breastfeeding.[2]
CoQ10 taken as a pharmacological substance has potential to inhibit the effects oftheophylline as well as theanticoagulantwarfarin; CoQ10 may interfere with warfarin's actions by interacting withcytochrome p450 enzymes thereby reducing theINR, a measure of blood clotting.[60] The structure of CoQ10 is similar to that ofvitamin K, which competes with and counteracts warfarin's anticoagulation effects. CoQ10 is not recommended in people taking warfarin due to the increased risk of clotting.[58]
Detailed reviews on occurrence of CoQ10 and dietary intake were published in 2010.[61] Besides the endogenous synthesis within organisms, CoQ10 also is supplied by various foods.[1] CoQ10 concentrations in various foods are:[1]
| Food | CoQ10 concentration (mg/kg) | |
|---|---|---|
| Vegetable oils | soybean oil | 54–280 |
| olive oil | 40–160 | |
| grapeseed oil | 64–73 | |
| sunflower oil | 4–15 | |
| canola oil | 64–73 | |
| 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 | |
| mackerel – white flesh | 11–16 | |
| salmon | 4–8 | |
| tuna | 5 | |
| 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 | |
Vegetable oils, meat, and fish are rich in CoQ10.[1]Dairy products are much poorer sources of CoQ10 than animal tissues. Among vegetables,broccoli andcauliflower are good sources of CoQ10.[1] Most fruits and berries are poor sources of CoQ10, exceptavocados, which have relatively high oil and CoQ10 content.[61]
In the developed world, the estimated daily intake of CoQ10 has been determined at 3–6 mg per day, derived primarily from meat.[61]
South Koreans have an estimated average daily CoQ (Q9 + Q10) intake of 11.6 mg/d, derived primarily fromkimchi.[62]
Cooking by frying reduces CoQ10 content by 14–32%.[63]
In 1950, a small amount of CoQ10 was isolated from the lining of a horse's gut, a compound initially calledsubstance SA, but later deemed to be quinone found in many animal tissues.[64] In 1957, the same compound was isolated frommitochondrial membranes of beef heart, with research showing that it transported electrons within mitochondria. It was calledQ-275 as a quinone.[64][65] The Q-275/substance SA was later renamedubiquinone as it was aubiquitous quinone found in all animal tissues.[64] In 1958, its full chemical structure was reported.[64][66] Ubiquinone was later called eithermitoquinone orcoenzyme Q due to its participation to the mitochondrial electron transport chain.[64] In 1966, a study reported that reduced CoQ6 was an effectiveantioxidant in cells.[67]
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This article incorporatespublic domain material from"Ubidecarenone".PubChem. US National Library of Medicine. 30 March 2024. Retrieved4 April 2024. This article incorporatespublic domain material fromCoenzyme Q10.National Cancer Institute. April 2022. This article incorporatespublic domain material fromWhite J (14 May 2014).PDQ Coenzyme Q10.National Cancer Institute,National Institutes of Health,U.S. Dept. of Health and Human Services. Retrieved29 June 2014. This article incorporates text from this source, which is available under theCC BY 4.0 license. This article incorporates text from this source, which is available under theCC BY 4.0 license.
