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COENZYME Q10: ANTIOXIDANT AS USEFUL TREATMENT ADJUNCT:

This is some thing I wrote as part of course work. Thought it is an intresting topics to be discussed.
I bring this in 3 parts. All your comments are important and is appreciated

COENZYME Q10: ANTIOXIDANT AS USEFUL TREATMENT ADJUNCT:

A REVIEW


Our body as an inbuilt defense mechanism, one of which is the defense against oxidative damage induced by the free radicals and/or reactive oxygen species. The in vivo anti oxidant defense systems are mainly of three kinds:

a) Preventive antioxidants, e.g.: Catalase, Glutathione peroxidase, S- transferase, Transferrin, albumin, haptoglobin, ceruloplasmin, Superoxide dismutase, carotenoids.

b) Radical scavengers E.g: Ubiquinol ( co-enzyme 10), vit A, vit E, carotenoids, uric acid, ascorbic acid, albumin, bilirubin.

c) Repair and de novo enzymes E.g: DNA repair enzymes, Protease, Transferase, Lipase.

Coenzyme Q10 (CoQ10) is an essential component of the mitochondria - the energy producing unit of the cells of our body. CoQ10 is involved in the manufacture of ATP, the energy currency of all body processes.

Coenzyme Q10 (CoQ10) is a vitamin-like substance, vital in the production of energy. It is also called as ubiquinone since it is found in every cell. CoQ10 was first isolated from beef heart mitochondria by Dr. Frederick Crane of Wisconsin, U.S.A., in 1957

Structure:
CoQ10 (2, 3-dimethoxy-5methylbenzoquione) is chemically classified as a fat-soluble quinone ring attached to 10 isoprene side units, structurally similar to vitamin K.

Biochemistry:
The primary action of CoQ10 is as a cofactor in the electron-transport chain. It is found in relatively high concentration in cells with high energy requirements such as heart, liver, muscle, and pancreas. Normal blood levels range from 0.7 - 1.0micro g/mL and the total body content is estimated to be 0.5 - 1.5g.

CoQ10 is synthesized in human cell in an eight-step pathway, from amino acid tyrosine, and vitamins such as folic acid, niacin, riboflavin, and pyridoxine.

Pharmacokinetics:
CoQ10 are well absorbed by oral supplementation a peak plasma levels are attained within 5 - 10 hours, with absorption being dependent on the fat presence in the gastrointestinal tract. The elimination half-life of the parent compound is approximately 34 hours; excretion is primarily through the biliary tract and over 60% of the oral dose is recovered in the feces.

Mechanism of Action:

Electron Transport Chain (ETC) to Produce ATP:

CoQ10, found in the inner mitochondrial membrane, is the cofactor for at least three mitochondrial enzymes that play a vital role in oxidative phosphorylation. Each pair of electrons processed by the ETC must interact with CoQ10, which is considered the rate-limiting constituent of the mitochondrial respiratory chain. Therefore; CoQ10 plays a essential role in ATP production.

Antioxidant:

CoQ10 acts to inhibit lipid and protein peroxidation and scavenges free radicals. It undergoes constant oxidation reduction recycling. In addition CoQ10 works synergistically with vitamin E, regenerating its active form, tocopherol, in the same synergistic mechanism as with vitamin C. CoQ10 is the only known naturally occurring lipid-soluble antioxidant that can be regenerated to its active form in the body.

Membrane Stabilization and Fluidity:

The membrane stabilizing property of Coq10 has been postulated to involve the phospholipid-protein interactions that increases prostaglandin (especially prostacyclin) metabolism. it is thought that CoQ10 stabilizes myocardial calcium-dependent ion channels and prevents the depletion of metabolites essential for ATP synthesis. CoQ10 also decreases blood viscosity, and improves blood flow to cardiac muscle in patients with ischemic heart disease.

Formulations and Dosage:

Exogenously CoQ10 are found in fish, fish oil, organ meats and germ of whole grains. The average diet is estimated to provide approximately 10mg/day of CoQ10.

Commercially available CoQ10 is produced by the fermentation of beets and sugar cane, using special strains of yeast. Dosage forms currently available include powder-filled capsules, powder-based tablets, soft gel capsules, fully solubilized soft gel capsules, chewable wafers, intravenous solution, and intra-oral spray.

Doses of 30-60 mg/day BID are generally recommended to prevent CoQ10 deficiency and to maintain normal serum concentrations of 0.7 -1.0µg/mL. For treatment of Chronic heart disease therapeutic doses of 100 -200mg/day are advocated and 90 -390mg/day for treatment of breast cancer. Divided doses are recommended to minimize adverse affects when doses exceed 100mg/day. Maximum absorption of CoQ10 can be achieved if taken with meals that contain fat.

CoQ10 Recommended Intake

Disease

Cardiovascular

Usual Doses

Chronic Heart Failure

100 – 200 mg

Stable Angina

150 – 200 mg

Hypertension

100 – 200 mg

Cardiotoxicity

50 mg

Cardiac Surgery/Arrhythmia

100 – 200 mg

Adverse effects:
Adverse effects with use of Coq10 have been minor and include epigastric discomfort, appetite suppression, nausea and diarrhea. These affects are dose related and are minimized with dose reduction or dose division. There is elevated serum LDH and SGOT levels with doses exceeding 300mg/day, but does not result in hepatotoxicity.

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