Coenzyme Q10
Names | |
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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 ) |
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ChEBI | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard
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100.005.590 |
KEGG | |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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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 | |
Related quinones
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1,4-Benzoquinone Plastoquinone Ubiquinol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Coenzyme Q10 (CoQ10 /ˌkoʊkjuːˈtɛn/) also known as ubiquinone, is a naturally occurring biochemical cofactor (coenzyme) and an antioxidant produced by the human body.[1][2][3] It can also be obtained from dietary sources, such as meat, fish, seed oils, vegetables, and dietary supplements.[1][2] CoQ10 is found in many organisms, including animals and bacteria.
CoQ10 plays a role in
Although a ubiquitous molecule in human tissues, CoQ10 is not a dietary nutrient, does not have a recommended intake level, and its use as a supplement is not associated with or approved for any health or anti-disease effect.[1][2]
Biological functions
CoQ10 is a component of the mitochondrial electron 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 a
The mitochondrial oxidative phosphorylation process takes place 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]
- electron transport in the mitochondrial ETC, by shuttling electrons from mitochondrial complexes like
- antioxidant activity as a lipid-soluble antioxidant together with vitamin E, scavenging reactive oxygen species and protecting cells against oxidative stress,[1][6] inhibiting the oxidation of proteins, DNA, and use of vitamin E.[1][9]
CoQ10 also may influence immune response by modulating the expression of genes involved in inflammation.[10][11][12]
Biochemistry
This article needs attention from an expert in biochemistry. See the WikiProject Biochemistry may be able to help recruit an expert. (April 2024) |
Coenzymes Q is a
Coenzyme Q10 is a 1,4-benzoquinone, in which "Q" refers to the quinone chemical group and "10" refers to the number of isoprenyl 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 respiring eukaryotic cells, primarily in the mitochondria.[1] Ninety-five percent of the human body's energy is generated this way.[15] Organs with the highest energy requirements—such as the heart, liver, and kidney—have the highest CoQ10 concentrations.[16][17][18][19]
There are three redox states of CoQ: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (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 the iron–sulfur clusters that can only accept one electron at a time, and as a free radical–scavenging antioxidant.[1][14]
Deficiency
There are two major pathways of deficiency of CoQ10 in humans: reduced
Assessment
Although CoQ10 may be measured in
Statins
While statins may reduce CoQ10 in the blood it is unclear if they reduce CoQ10 in muscle.[26] Evidence does not support that supplementation improves side effects from statins.[26] However, a more recent metanalysis conducted in China, one of the world's largest producers of this supplement, concluded that, "CoQ10 supplementation ameliorated SAMSs [statin‐associated muscle symptoms], implying that CoQ10 supplementation might be a complementary approach to ameliorate statin‐induced myopathy."[27]
Chemical properties
The oxidized structure of CoQ10 is shown below. The various kinds of coenzyme Q may be distinguished by the number of
In its pure state, it is an orange-colored lipophile powder, and has no taste nor odor.[14]
Biosynthesis
Biosynthesis occurs in most human tissue. There are three major steps:
- Creation of the 4-hydroxybenzoate)
- Creation of the isoprene side chain (using acetyl-CoA)
- The joining or condensation of the above two structures
The initial two reactions occur in
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 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.[24][26]
Genes involved include PDSS1, PDSS2, COQ2, and ADCK3 (COQ8, CABC1).[29]
Organisms other than humans produce the benzoquinone and isoprene structures from somewhat different source chemicals. For example, the bacteria
Dietary supplement
Although neither a
Nevertheless, CoQ10 is widely available as an over-the-counter dietary supplement and is recommended by some healthcare professionals, despite of lack of definitive scientific evidence supporting these recommendations.[1][3]
Regulation and composition
CoQ10 is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of any medical condition.[32][33][34][35] However, it is sold as a dietary supplement not subject to the same regulations as medicinal drugs, and is an ingredient in some cosmetics.[36] The manufacture of CoQ10 is not regulated, and different batches and brands may vary significantly.[34]
Research
A 2014
A 2017 meta-analysis of people with heart failure 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.[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 used to treat purported muscle-related side effects of statin medications, a 2015 meta-analysis found that CoQ10 had no effect on statin myopathy.[42] 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.[27]
Pharmacology
Absorption
CoQ10 in the pure form is a
Metabolism
CoQ10 is metabolized in all tissues, with the metabolites being phosphorylated in cells.[2] CoQ10 is reduced to ubiquinol during or after absorption in the small intestine.[2] It is absorbed by chylomicrons, and redistributed in the blood within lipoproteins.[2] Its elimination occurs via biliary and fecal excretion.[2]
Pharmacokinetics
Some reports have been published on the pharmacokinetics 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 also was observed at approximately 24 hours after administration, probably due to both enterohepatic recycling and redistribution from the liver to circulation.[43]
Deuterium-labeled crystalline CoQ10 was used to investigate pharmacokinetics in humans to determine an elimination half-time of 33 hours.[46]
Bioavailability
In contrast to 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.[47][48] Bioavailability of CoQ10 supplements may be reduced due to the lipophilic nature of its molecule and large molecular weight.[47]
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.[49] However, this has not proved successful with CoQ10, although reports have differed widely.[50][51] The use of aqueous suspension of finely powdered CoQ10 in pure water also reveals only a minor effect.[52]
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.
Adverse effects and precautions
Generally, oral CoQ10 supplementation is well tolerated.
Use of CoQ10 supplementation is not recommended in people with liver or kidney disease, during pregnancy or breastfeeding, or in the elderly.[2]
Potential drug interactions
CoQ10 taken as a pharmacological substance has potential to inhibit the effects of
Dietary concentrations
Detailed reviews on occurrence of CoQ10 and dietary intake were published in 2010.[60] 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 quite rich in CoQ10 levels.[1] Dairy products are much poorer sources of CoQ10 than animal tissues. Among vegetables, broccoli and cauliflower are good sources of CoQ10.[1] Most fruit and berries are poor sources of CoQ10, with the exception of avocados, which have a relatively high oil and CoQ10 content.[60]
Intake
In the developed world, the estimated daily intake of CoQ10 has been determined at 3–6 mg per day, derived primarily from meat.[60]
South Koreans have an estimated average daily CoQ (Q9 + Q10) intake of 11.6 mg/d, derived primarily from kimchi.[61]
Effect of heat and processing
Cooking by frying reduces CoQ10 content by 14–32%.[62]
History
In 1950, a small amount of CoQ10 was isolated from the lining of a horse's gut, a compound initially called substance SA, but later deemed to be quinone found in many animal tissues.
See also
- Idebenone – synthetic analog with reduced oxidant generating properties
- Mitoquinone mesylate – synthetic analog with improved mitochondrial permeability
References
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