Coenzyme Q10

Absorption

Ubidecarenone is absorbed from the small intestine into the lymphatics and then it can enter the blood. The hydrophobicity and large molecular weight limit its absorption making it very poor and variable depending on the food intake and the number of lipids presented in the food. The absorption is lower in the presence of an empty stomach and greater in presence of high lipid food diet. The daily dosage of ubidecarenone presents the reach of maximal serum concentration by reaching a plateau after three weeks. The pharmacokinetic properties may vary between different brands but studies have reported an AUC of 11.51 mcg h/ml and a Cmax of 0.32 mcg/ml at a time of 7.9 h.

Toxicity

There have not been reports of adverse events of diet supplementation with ubidecarenone. The normal side effects reported in humans are related to the gastrointestinal tract.

Description

Coenzyme Q10 (CoQ10) is a quinone that is found throughout the human body in cell membranes, primarily in mitochondrial membranes, with the highest levels in the heart, lungs, liver, kidneys, spleen, pancreas, and adrenal glands. It exists in three redox states: fully oxidized (CoQ10/ubiquinone), partially reduced (semiquinone or ubisemiquinone), and fully reduced (ubiquinol; ). Cholesterol-reducing statins deplete the body’s CoQ10, and many statin users take 100 mg or more CoQ10 per day as a nutritional supplement. Some physicians recommend taking the reduced form, ubiquinol, because it may be absorbed by the body better than ubiquinone.

Chemical properties

Yellow-Orange Crystalline Powder

Originator

Neuquinon,Eisai,Japan,1974

Occurrence

Coenzyme Q10 is found in dietary sources. Coenzyme Qmolecules have side chains of differentlengths in different types of organismsbut function in similar ways.

The Uses of Coenzyme Q10

Coenzyme Q10 is a mitochondrial transporter chain component, and it is a powerful antioxidant that is naturally found in the cells. It acts as a free radical neutraliser.

The Uses of Coenzyme Q10

Coenzyme Q10 (CoQ10) is a naturally occurring quinone found throughout the body in cell membranes, primarily in mitochondrial membranes, with highest concentrations in the heart, lungs, liver, kidneys, spleen, pancreas, and adrenal glands. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. In its reduced form, CoQ10 acts as an antioxidant, preventing the formation of reactive oxygen species. CoQ10 deficiencies have been associated with heart failure, hypertension, parkinsonism, mitochondrial encephalomyopathies, and other chronic diseases.[Cayman Chemical]

Indications

The diet supplements containing ubidecarenone are indicated, as stated in the product label, to assist individuals with cardiovascular complaints including congestive heart failure and systolic hypertension. In the product, ubidecarenone is used to increase the cardiac input as well as for the prevention of several other diseases like Parkinson, fibromyalgia, migraine, periodontal disease and diabetes, based on preclinical studies. It is important to highlight that these products are not FDA approved and it is recommended to use under discretion.

Background

Ubidecarenone, also called coenzyme Q10, is a 1,4-benzoquinone. From its name (Q10), the Q refers to the constitutive quinone group, and 10 is related to the number of isoprenyl subunits in its tail. It is a powerful antioxidant, a lipid-soluble and essential cofactor in mitochondrial oxidative phosphorylation. The ubidecarenone is the coenzyme destined for mitochondrial enzyme complexes involved in oxidative phosphorylation in the production of ATP. It is fundamental for cells that have a high metabolic demand. Ubidecarenone is sold as a dietary supplement and is not FDA approved as a drug - it is not meant to treat, cure or prevent any disease. FDA does not approve this dietary supplements before sold nor regulate the manufacturing process.

Definition

ChEBI: Coenzyme Q10 is a ubiquinone having a side chain of 10 isoprenoid units. In the naturally occurring isomer, all isoprenyl double bonds are in the E- configuration. It has a role as a human metabolite, a ferroptosis inhibitor and an antioxidant. It is found in animal organs and yeast with active in the citric acid cycle in carbohydrate metabolism.

Manufacturing Process

A small fermentation tank (5,000 parts by volume capacity) was charged with 3,000 parts by volume of a culture medium (pH 6.0) comprising 3% glucose, 1% polypepton, 0.5% yeast extract and 0.5% malt extract. The medium was sterilized by heating in a conventional manner and cooled. This medium was inoculated with 150 parts by volume of a pre-culture of Sporidiobolus ruinenii CBS-5001, which had been prepared by growing the same strain on a medium of the same composition as above at 28°C for one day. The inoculated medium was incubated at 28°C and under agitation at 800 rpm with sparging at a rate of 3,000 parts by volume per minute for 24 hours. During this fermentation period, the medium was maintained at pH 6.0 with ammonia and sulfuric acid.
The resultant fermentation broth was centrifuged to harvest the microbial cells, and they were washed with water and centrifuged a second time, whereupon a living cell paste was obtained. (There was obtained an amount of cells equivalent to 54 parts on a dry basis, which contained 920 μg of ubiquinone-10 per gram of dry cells.)
The moist cells were suspended in 750 parts of volume of ethanol and extracted by warming at 60°C for 1 hour. A total of 3 extractions were carried out in a similar manner and the extracts were pooled, diluted with water and further extracted three times with 1,000 parts of volume portions of n_x0002_hexane. The n-hexane layer was concentrated to dryness under reduced pressure to recover 4.12 parts of a yellow oil. This oily residue was dissolved in 6 parts by volume of benzene and passed through a column (500 parts by volume capacity) packed with Floridil (100 to 200 meshes). Elution was carried out using benzene and the eluate was collected in 10 parts by volume fractions. Each fraction was analyzed by thin-layer chromatography and color reaction and the fractions rich in ubiquinone-10 were pooled and concentrated under reduced pressure. By this procedure was obtained 0.562 part of a yellow oil. This product was dissolved in 5 parts by volume of chloroform, coated onto a thin layer plate of silica gel GF254 (silica gel with calcium sulfate) and developed with benzene. The fractions corresponding to ubiquinone-10 were extracted, whereby 0.054 part of a yellow oil was obtained. This oil was dissolved in 10 parts by volume of ethanol and allowed to cool, whereupon 0.029 part of yellow crystals of ubiquinone-10 were obtained, its melting point 48° to 50°C.
There are also synthetic routes to the ubiquinones as described in US Patents 3,068,295; 3,896,153 and 4,062,879.

Therapeutic Function

UBIDECARENONE

General Description

Ubidecarenone, referred to as coenzyme Q, is abundantly available in human cells, with major proportions being present in vital body organs such as heart and kidneys. It plays an important role in cell metabolism owing to its significant contribution to the electron transport pathway. It is a strong antioxidant and acts as an essential enzyme catalyst in mitochondrial oxidative phosphorylation.

Biological Activity

Component of the mitochondrial transporter chain that behaves as a powerful antioxidant. Displays neuroprotective activity.

Biochem/physiol Actions

Coenzyme Q10 is an endogenous cellular antioxidant and an essential component of the electron transfer chain. CoQ10 takes part in aerobic cellular respiration and generation of energy in the form of ATP.

Pharmacokinetics

Coenzyme Q10 has roles in many prysiological process including sulfide oxidation, regulation of mitochondrial permeability transition pore and translocation of protons and calcium ions accross biological membranes. Studies have shown its benefitial effect in treating cancer, statin myopathy, congestive heart failure and hypertension.

Side Effects

Mild side effects might include digestive problems such as: Upper abdominal pain; Loss of appetite; Nausea and vomiting; Diarrhea.
Other possible side effects may include: Headaches and dizziness; Insomnia; Fatigue; Skin itching or rashes; Irritability or agitation.

Drug interactions

Coenzyme Q10 supplements may interact with some antihypertensive (those that lower blood pressure) and chemotherapy drugs. Coenzyme Q10 may increase the risk of blood clots in people who take the anticoagulant warfarin by decreasing warfarin's effectiveness.

Metabolism

Studies indicate that there is no saturation process during the metabolism of ubidecarenone. It is metabolized in all tissues by the phosphorylation in the cells and transportation to the kidneys for further excretion by the urine. After exerting its action, ubidecarenone is reduced and forms hydroquinone which is capable of recycling and regenerates other antioxidants such as tocopherol and ascorbate. The later metabolism of hydroquinone generates the formation of Q acid I and Q acid II in free and conjugated forms.

Purification Methods

Purify it by recrystallisation from EtOH, EtOH/Me2CO or Et2O/EtOH and by chromatography on silica gel using isoPrOH/Et2O (3:1) to give orange crystals. It has max 270nm ( 15,170) in pet ether. [Terao et al. J Org Chem 44 868 1979, NMR and MS: Naruta et al. J Org Chem 45 4097 1980, IR: Lester et al. Biochem Biophys Acta 42 1278 1959, NMR: Planta et al. Helv Chim Acta 42 1278 1959; Morton Biochemical Spectroscopy (Adam Hilger, London, 1975) p 491].