Coenzyme Q, also known as ubiquinone and marketed as CoQ10, is a
coenzyme
A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that ass ...
family that is
ubiquitous
Omnipresence or ubiquity is the property of being present anywhere and everywhere. The term omnipresence is most often used in a religious context as an attribute of a deity or supreme being, while the term ubiquity is generally used to describ ...
in animals and most
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
(hence the name ubiquinone). In humans, the most common form is coenzyme Q
10 or ubiquinone-10.
It is a
1,4-benzoquinone
1,4-Benzoquinone, commonly known as ''para''-quinone, is a chemical compound with the formula C6H4O2. In a pure state, it forms bright-yellow crystals with a characteristic irritating odor, resembling that of chlorine, bleach, and hot plastic o ...
, where Q refers to the
quinone
The quinones are a class of organic compounds that are formally "derived from aromatic compounds uch as benzene or naphthaleneby conversion of an even number of –CH= groups into –C(=O)– groups with any necessary rearrangement of double ...
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 resemble
vitamin
A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an Nutrient#Essential nutrients, essential micronutrient that an organism needs in small quantities for the proper functioning of its ...
s, is present in all respiring
eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cells, primarily in the
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
. It is a component of the
electron transport chain
An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
and participates in
aerobic cellular respiration
Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor such as oxygen to produce large amounts of energy, to drive the bulk production of ATP. Cellular respiration may be des ...
, which generates energy in the form of
ATP. Ninety-five percent of the human body's energy is generated this way. Organs with the highest energy requirements—such as the
heart
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
,
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, and
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
—have the highest CoQ
10 concentrations.
There are three
redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...
states of CoQ: fully oxidized (ubiquinone),
semiquinone (ubisemiquinone), and fully
reduced (
ubiquinol
A ubiquinol is an electron-rich (reduced) form of coenzyme Q (ubiquinone). The term most often refers to ubiquinol-10, with a 10-unit tail most commonly found in humans.
The natural ubiquinol form of coenzyme Q is 2,3-dimethoxy-5-methyl-6-poly ...
). 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 cluster
Iron–sulfur clusters (or iron–sulphur clusters in British spelling) are molecular ensembles of iron and sulfide. They are most often discussed in the context of the biological role for iron–sulfur proteins, which are pervasive. Many Fe– ...
s that can only accept one electron at a time, and as a
free-radical
In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron.
With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spon ...
–scavenging
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
.
Deficiency and toxicity
There are two major pathways of deficiency of CoQ
10 in humans: reduced
biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
, and increased use by the body. Biosynthesis is the major source of CoQ
10. Biosynthesis requires at least 12
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s, and mutations in many of them cause CoQ deficiency. CoQ
10 levels also may be affected by other genetic defects (such as mutations of
mitochondrial DNA
Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, such as adenosine triphosphate (ATP). Mitochondrial D ...
, ''
ETFDH
Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial is an enzyme that in humans is encoded by the ''ETFDH'' gene. This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron tra ...
'', ''
APTX
aptX (''apt'' stands for ''audio processing technology'') is a family of proprietary audio codec
An audio codec is a device or computer program capable of encoding or decoding a digital data stream (a codec) that encodes or decodes audio. In s ...
'', ''
FXN
Frataxin is a protein that in humans is encoded by the FXN gene.
It is located in the mitochondrion and Frataxin mRNA is mostly expressed in tissues with a high metabolic rate. The function of frataxin is not clear but it is involved in assemb ...
'', and ''
BRAF'', genes that are not directly related to the CoQ
10 biosynthetic process). Some of these, such as mutations in ''
COQ6
Coenzyme Q6 monooxygenase is a protein that in humans is encoded by the COQ6 gene.
Function
The protein encoded by this gene belongs to the ubiH/COQ6 family. It is an evolutionarily conserved monooxygenase required for the biosynthesis of coenz ...
'', can lead to serious diseases such as steroid-resistant
nephrotic syndrome with sensorineural
deafness
Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...
.
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.
Assessment
Although CoQ
10 may be measured in
blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...
, these measurements reflect dietary intake rather than tissue status. Currently, most clinical centers measure CoQ
10 levels in cultured skin
fibroblast
A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
s, muscle
biopsies
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
, 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.
]
Statins
It has been suggested that the myo-toxicity of statin
Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs.
Low ...
s is due to impairment of CoQ biosynthesis, but the evidence supporting this was deemed controversial in 2011.
While statins may reduce coenzyme Q10 in the blood it is unclear if they reduce coenzyme Q10 in muscle.[ Evidence does not support that supplementation improves side effects from statins.] However, a more recent metanalysis conducted in China, one of the world's largest producers of this supplement, concluded that, "CoQ10 supplementation ameliorated SAMSs, implying that CoQ10 supplementation might be a complementary approach to ameliorate statin‐induced myopathy."
Dietary supplement
Regulation and composition
CoQ10 is not approved by the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) for the treatment of any medical condition;. However, it is sold as a dietary supplement
A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
in the name of UbiQ 300 & UbiQ 100, not subject to the same regulations as medicinal drugs, and is an ingredient in some cosmetics. The manufacture of CoQ10 is not regulated, and different batches and brands may vary significantly:[ a 2004 laboratory analysis by ConsumerLab.com of CoQ10 supplements on sale in the US found that some did not contain the quantity identified on the product label. Amounts ranged from "no detectable CoQ10", through 75% of stated dose, up to a 75% excess.
Generally, CoQ10 is well tolerated. The most common side effects are gastrointestinal symptoms (]nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
, appetite suppression
An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic.
The term is (from the Greek ''ἀν-'' (an-) = "without" and ...
, and abdominal pain
Abdominal pain, also known as a stomach ache, is a symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...
), rash
A rash is a change of the human skin which affects its color, appearance, or texture.
A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...
es, and headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
s.
While there is no established ideal dosage of CoQ10, a typical daily dose is 100–200 milligrams. Different formulations have varying declared amounts of CoQ10 and other ingredients.
Heart disease
A 2014 Cochrane review
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profes ...
found "no convincing evidence to support or refute" the use of CoQ10 for the treatment of heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
. 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 effect on blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
.
In a 2017 meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
of people with heart failure 30–100 mg/d of CoQ10 resulted in 31% lower mortality. Exercise capacity was also increased. No significant difference was found in the endpoints of left heart ejection fraction and New York Heart Association (NYHA) classification.
Migraine headaches
The Canadian Headache Society guideline for migraine prophylaxis
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
recommends, based on low-quality evidence, that 300 mg of CoQ10 be offered as a choice for prophylaxis.
Statin myopathy
CoQ10 has been routinely used to treat muscle breakdown associated as a side effect of use of statin
Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs.
Low ...
medications. A 2015 meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
of randomized controlled trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...
s found that CoQ10 had no effect on statin myopathy
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
. 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.
Cancer
no large clinical trials of CoQ10 in cancer treatment
Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. ...
had been conducted.[ The US' ]National Cancer Institute
The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
identified issues with the few, small studies that had been carried out, 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
The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
concluded, "CoQ10 may reduce the effectiveness of chemo and radiation therapy, so most oncologists would recommend avoiding it during cancer treatment."
Dental disease
A 1995 review study found that there is no clinical benefit to the use of CoQ10 in the treatment of periodontal disease
Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main caus ...
. Most of the studies suggesting otherwise were outdated, focused on in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
tests, had too few test subjects and/or erroneous statistical methodology and trial setup, or were sponsored by a manufacturer of the product.
Chronic kidney disease
A review of the effects of CoQ10 supplementation in people with CKD was proposed in 2019.
Additional uses
Coenzyme Q10 has also been used to treat Alzheimer's disease, high cholesterol, or amyotrophic lateral sclerosis (Lou Gehrig's disease). However, research has shown that it may not be effective in treating these conditions.
Coenzyme Q10 has also been utilized as an active ingredient in cosmeceuticals and as an inactive ingredient in sunscreen
Sunscreen, also known as sunblock or sun cream, is a photoprotective topical product for the skin that mainly absorbs, or to a much lesser extent reflects, some of the sun's ultraviolet (UV) radiation and thus helps protect against sunburn and ...
formulations. When applied topically in skincare products it demonstrates some ability to reduce oxidative stress in the skin, delay signs of intrinsic skin aging, reverse signs of extrinsic skin aging, assist in fading dyspigmentation, increase stability of certain sunscreen actives, increase the SPF of sunscreens, and afford some infrared
Infrared (IR), sometimes called infrared light, is electromagnetic radiation (EMR) with wavelengths longer than those of visible light. It is therefore invisible to the human eye. IR is generally understood to encompass wavelengths from around ...
protection to sunscreens. Much of the research on the skin benefits of ubiquinone show that it works synergistically with other topical antioxidants to improve the skin and cosmetic formulations.
Interactions
Coenzyme Q10 has potential to inhibit the effects of theophylline
Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
as well as the anticoagulant
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...
warfarin
Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent st ...
; coenzyme Q10 may interfere with warfarin's actions by interacting with cytochrome p450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
enzymes thereby reducing the INR, a measure of blood clotting. The structure of coenzyme Q10 is very similar to that of vitamin K
Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...
, 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.[
]
Chemical properties
The oxidized structure of CoQ10 is shown above. 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.
:
In its pure state, it is an orange-coloured lipophile powder, and has no taste nor odour.
Biosynthesis
Biosynthesis occurs in most human tissue. There are three major steps:
# Creation of the benzoquinone Benzoquinone (C6H4O2) is a quinone with a single benzene ring. There are 2 (out of 3 hypothetical) benzoquinones:
* 1,4-Benzoquinone, most commonly, right image (also ''para''-benzoquinone, ''p''-benzoquinone, ''para''-quinone, or just quinone)
* 1 ...
structure (using phenylalanine
Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...
or tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
, via 4-hydroxybenzoate)
# Creation of the isoprene
Isoprene, or 2-methyl-1,3-butadiene, is a common volatile organic compound with the formula CH2=C(CH3)−CH=CH2. In its pure form it is a colorless volatile liquid. Isoprene is an unsaturated hydrocarbon. It is produced by many plants and animals ...
side chain (using acetyl-CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...
)
# The joining or condensation
Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor to ...
of the above two structures
The initial two reactions occur in mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
, the endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
, and peroxisome
A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pero ...
s, indicating multiple sites of synthesis in animal cells.
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
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
and rhabdomyolysis
Rhabdomyolysis (also called rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of th ...
. 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 medications.[
Genes involved include '']PDSS1
Decaprenyl-diphosphate synthase subunit 1 is an enzyme that in humans is encoded by the ''PDSS1'' gene.
The protein encoded by this gene is an enzyme that elongates the prenyl side-chain of coenzyme Q, or ubiquinone
Coenzyme Q, also known a ...
'', ''PDSS2
Decaprenyl-diphosphate synthase subunit 2 (PDSS2) is a protein that in humans is encoded by the ''PDSS2'' gene.
Function
The protein encoded by this gene is an enzyme that synthesizes the prenyl side-chain of coenzyme Q, or ubiquinone, one of ...
'', ''COQ2
Para-hydroxybenzoate—polyprenyltransferase, mitochondrial is an enzyme that in humans is encoded by the ''COQ2'' gene.
CoQ ( ubiquinone) serves as a redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the ...
'', and ''ADCK3
aarF domain containing kinase 3 is a protein that in humans is encoded by the ''ADCK3'' gene.
This gene encodes a mitochondrial protein similar to yeast ABC1, which functions in an electron-transferring membrane protein complex in the respirat ...
'' (''COQ8'', ''CABC1'').
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
Chorismic acid, more commonly known as its anionic form chorismate, is an important biochemical intermediate in plants and microorganisms. It is a precursor for:
* The aromatic amino acids phenylalanine, tryptophan, and tyrosine
* Indole, indole ...
and the latter from a non-mevalonate
Mevalonic acid (MVA) is a key organic compound in biochemistry; the name is a contraction of dihydroxymethylvalerolactone. The carboxylate anion of mevalonic acid, which is the predominant form in biological environments, is known as ''mevalonate ...
source. The common yeast ''S. cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have bee ...
'', however, derives the former from either chorismate or tyrosine and the latter from mevalonate
Mevalonic acid (MVA) is a key organic compound in biochemistry; the name is a contraction of dihydroxymethylvalerolactone. The carboxylate anion of mevalonic acid, which is the predominant form in biological environments, is known as ''mevalonate ...
. Most organisms share the common 4-hydroxybenzoate intermediate, yet again uses different steps to arrive at the "Q" structure.
Absorption and metabolism
Absorption
CoQ10 is a crystal
A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macros ...
line 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
Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitami ...
, another lipid-soluble nutrient. This process in the human body involves secretion 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
into the small intestine
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...
of pancreatic enzymes and bile
Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile ...
, which facilitates emulsification
An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Altho ...
and micelle
A micelle () or micella () (plural micelles or micellae, respectively) is an aggregate (or supramolecular assembly) of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloidal suspension (also known as associated collo ...
formation required for absorption of lipophilic
Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipop ...
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.
Metabolism
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
A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates.
Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...
and fecal
Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a relati ...
excretion
Excretion is a process in which metabolic waste
is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after ...
. After the withdrawal of CoQ10 supplementation, the levels return to normal within a few days, irrespective of the type of formulation used.
Pharmacokinetics
Some reports have been published on the pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
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
Nanoparticle
A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 1 ...
s have been explored as a delivery system for various drugs, such as improving the oral bioavailability of drugs with poor absorption characteristics. However, this has not proved successful with CoQ10, although reports have differed widely. The use of aqueous suspension
Suspension or suspended may refer to:
Science and engineering
* Suspension (topology), in mathematics
* Suspension (dynamical systems), in mathematics
* Suspension of a ring, in mathematics
* Suspension (chemistry), small solid particles suspend ...
of finely powdered CoQ10 in pure water also reveals only a minor effect.
Soft-gel capsules with CoQ10 in oil suspension
A successful approach is to use the emulsion
An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Althoug ...
system to facilitate absorption from the gastrointestinal tract and to improve bioavailability. Emulsions of soybean oil
Soybean oil (British English: soyabean oil) is a vegetable oil extracted from the seeds of the soybean (''Glycine max''). It is one of the most widely consumed cooking oils and the second most consumed vegetable oil. As a drying oil, processed s ...
(lipid microspheres) could be stabilised very effectively by lecithin
Lecithin (, from the Greek ''lekithos'' "yolk") is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues which are amphiphilic – they attract both water and fatty substances (and so ar ...
and were used in the preparation of softgel
A softgel is an oral dosage form for medicine in the form of a specialized capsule. They consist of a gelatin based shell surrounding a liquid fill. Softgel shells are a combination of gelatin, water, opacifier and a plasticiser such as glyceri ...
capsules. In one of the first such attempts, Ozawa ''et al.'' performed a pharmacokinetic study on beagle
The beagle is a breed of small scent hound, similar in appearance to the much larger foxhound. The beagle was developed primarily for hunting hare, known as beagling. Possessing a great sense of smell and superior tracking instincts, the ...
s 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 ucapsules 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
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
tyloxapol
Tyloxapol is a nonionic liquid polymer of the alkyl aryl polyether alcohol type. It is used as a surfactant to aid liquefaction and removal of mucopurulent (containing mucus and pus) bronchopulmonary secretions, administered by inhalation through ...
, formulations based on various solubilising agents, such as hydrogenated lecithin
Lecithin (, from the Greek ''lekithos'' "yolk") is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues which are amphiphilic – they attract both water and fatty substances (and so ar ...
, and complexation
A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...
with cyclodextrins; among the latter, the complex with β-cyclodextrin
β-Cyclodextrin sometimes abbreviated as β-CD, is a heptasaccharide derived from glucose. The α- (alpha), β- (beta), and γ- (gamma) cyclodextrins correspond to six, seven, and eight glucose units, respectively. β-Cyclodextrin is the most used ...
has been found to have highly increased bioavailability and also is used in pharmaceutical and food industries for CoQ10-fortification.
History
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
Liverpool is a city and metropolitan borough in Merseyside, England. With a population of in 2019, it is the 10th largest English district by population and its metropolitan area is the fifth largest in the United Kingdom, with a popul ...
, England. In subsequent studies the compound was briefly called ''substance SA'', it was deemed to be quinone
The quinones are a class of organic compounds that are formally "derived from aromatic compounds uch as benzene or naphthaleneby conversion of an even number of –CH= groups into –C(=O)– groups with any necessary rearrangement of double ...
and it was noted that it could be found from many tissues of a number of animals.
In 1957, Frederick L. Crane and colleagues at the University of Wisconsin–Madison
A university () is an educational institution, institution of higher education, higher (or Tertiary education, tertiary) education and research which awards academic degrees in several Discipline (academia), academic disciplines. Universities ty ...
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
The quinones are a class of organic compounds that are formally "derived from aromatic compounds uch as benzene or naphthaleneby conversion of an even number of –CH= groups into –C(=O)– groups with any necessary rearrangement of double ...
. 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 a 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
Karl August Folkers (September 1, 1906 – December 7, 1997) was an American biochemist who made major contributions to the isolation and identification of bioactive natural products.
Career
Folkers graduated from the College of Liberal Arts a ...
at Merck
Merck refers primarily to the German Merck family and three companies founded by the family, including:
* the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668
** Merck Serono (known as EMD Serono in the Unite ...
in Rahway
Rahway () is a city in southern Union County, in the U.S. state of New Jersey. A bedroom community of New York City, it is centrally located in the Rahway Valley region, in the New York metropolitan area. The city is southwest of Manhattan ...
. 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
An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
.
In 1966, A. Mellors and A. L. Tappel at the University of California
The University of California (UC) is a public land-grant research university system in the U.S. state of California. The system is composed of the campuses at Berkeley, Davis, Irvine, Los Angeles, Merced, Riverside, San Diego, San Francisco, ...
were the first to show that reduced CoQ6 was an effective antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
in cells.
In 1960s Peter D. Mitchell
Peter Dennis Mitchell, FRS (29 September 1920 – 10 April 1992) was a British biochemist who was awarded the 1978 Nobel Prize for Chemistry for his discovery of the chemiosmotic mechanism of ATP synthesis.
Education and early life
Mitc ...
enlarged upon the understanding of mitochondrial function via his theory of electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and th ...
, which involves CoQ10, and in late 1970s studies of Lars Ernster
Lars Ernster ( hu, Ernster László; 4 May 1920 – 4 November 1998) was a professor of biochemistry, and a member of the Board of the Nobel Foundation.
Biography
Lars Ernster was born in Hungary and came to Sweden in 1946. He played a promine ...
enlargened upon the importance of CoQ10 as an antioxidant. The 1980s witnessed a steep rise in the number of clinical trials involving CoQ10.
Dietary concentrations
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:
Vegetable oil
Vegetable oils, or vegetable fats, are oils extracted from seeds or from other parts of fruits. Like animal fats, vegetable fats are ''mixtures'' of triglycerides. Soybean oil, grape seed oil, and cocoa butter are examples of seed oils, or fat ...
s are the richest sources of dietary CoQ10; Meat and fish also are quite rich in CoQ10 levels over 50 mg/kg may be found in beef
Beef is the culinary name for meat from cattle (''Bos taurus'').
In prehistoric times, humankind hunted aurochs and later domesticated them. Since that time, numerous breeds of cattle have been bred specifically for the quality or quantity ...
, pork
Pork is the culinary name for the meat of the domestic pig (''Sus domesticus''). It is the most commonly consumed meat worldwide, with evidence of pig husbandry dating back to 5000 BCE.
Pork is eaten both freshly cooked and preserved; ...
, and chicken heart and liver. Dairy product
Dairy products or milk products, also known as lacticinia, are food products made from (or containing) milk. The most common dairy animals are cow, water buffalo, nanny goat, and ewe. Dairy products include common grocery store food items in th ...
s are much poorer sources of CoQ10 than animal tissues. Within vegetables, parsley
Parsley, or garden parsley (''Petroselinum crispum'') is a species of flowering plant in the family Apiaceae that is native to the central and eastern Mediterranean region (Sardinia, Lebanon, Israel, Cyprus, Turkey, southern Italy, Greece, Por ...
and perilla
''Perilla'' is a genus consisting of one major Asiatic crop species ''Perilla frutescens'' and a few wild species in nature belonging to the mint family, Lamiaceae. The genus encompasses several distinct varieties of Asian herb, seed, and veget ...
are the richest CoQ10 sources, but significant differences in their CoQ10 levels may be found in the literature. Broccoli
Broccoli (''Brassica oleracea'' var. ''italica'') is an edible green plant in the cabbage family (family Brassicaceae, genus ''Brassica'') whose large flowering head, stalk and small associated leaves are eaten as a vegetable. Broccoli is cl ...
, grape
A grape is a fruit, botanically a berry, of the deciduous woody vines of the flowering plant genus ''Vitis''. Grapes are a non- climacteric type of fruit, generally occurring in clusters.
The cultivation of grapes began perhaps 8,000 years ago, ...
s, and cauliflower
Cauliflower is one of several vegetables in the species ''Brassica oleracea'' in the genus ''Brassica'', which is in the Brassicaceae (or mustard) family. It is an annual plant that reproduces by seed. Typically, only the head is eaten – the ...
are modest sources of CoQ10. Most fruit and berries represent a poor to very poor source of CoQ10, with the exception of avocado
The avocado (''Persea americana'') is a medium-sized, evergreen tree in the laurel family (Lauraceae). It is native to the Americas and was first domesticated by Mesoamerican tribes more than 5,000 years ago. Then as now it was prized for i ...
s, which have a relatively high CoQ10 content.
Intake
In the developed world, the estimated daily intake of CoQ10 has been determined at 3–6 mg per day, derived primarily from meat.
South Koreans have an estimated average daily CoQ (Q9 + Q10) intake of 11.6 mg/d, derived primarily from kimchi
''Kimchi'' (; ko, 김치, gimchi, ), is a traditional Korean side dish of salted and fermented vegetables, such as napa cabbage and Korean radish. A wide selection of seasonings are used, including ''gochugaru'' (Korean chili powder), sprin ...
.
Effect of heat and processing
Cooking by frying reduces CoQ10 content by 14–32%.
See also
*Idebenone
Idebenone (pronounced eye-deb-eh-known, trade names Catena, Raxone, Sovrima, among others) is a drug that was initially developed by Takeda Pharmaceutical Company for the treatment of Alzheimer's disease and other cognitive defects. This has bee ...
– synthetic analog with reduced oxidant generating properties
* Mitoquinone mesylate – synthetic analog with improved mitochondrial permeability
References
External links
*
*
*
{{Antioxidants
Antioxidants
1,4-Benzoquinones
Cellular respiration
Coenzymes
Dietary antioxidants
Glycolysis
Phenol ethers
Polyenes