Article: Coenzyme Q

Coenzyme Q (CoQ), also known as ubiquinone or ubiquinol, is a biologically active quinone with an isoprenoid side chain, related in structure to vitamin K and vitamin E.

History

Coenzyme Q was first discovered in 1957 by professor F. L. Crane and colleagues at the University of Wisconsin Enzyme Institute. In 1958, its chemical structure was reported by Dr. D.E. Wolf and a research group at Merck Laboratories led by Dr. Karl Folkers.

Chemical properties

The oxidized structure of CoQ, or Q, is given here:

The various kinds of Coenzyme Q can be distinguished by the number of isoprenoid side chains they have. The most common CoQ in human mitochondria is Q₁₀. The image above has three isoprenoid units and would be called Q₃.

If Coenzyme Q is reduced by one equivalent, the following structure results, a ubisemiquinone, and is denoted QH. Note the free radical on one of the ring oxygens (either oxygen may become a free radical, in this case the top oxygen is shown as such).

If Coenzyme Q is reduced by two equivalents, the compound becomes a ubiquinol, denoted QH₂:

Biochemical role

CoQ is found in the membranes of endoplasmic reticulum, peroxisomes, lysosomes, vesicles and notably the inner membrane of the mitochondrion where it is an important part of the electron transport chain; there it passes reducing equivalents to acceptors such as Coenzyme Q - cytochrome c reductase:

CoQH₂+ 2 Fe⁺³-cytochrome c → CoQ + 2 Fe⁺²-cytochrome c

In bacteria CoQ is involved in direct electron transfer towards oxygen:

CoQH₂ + O₂ → CoQ + H₂O

CoQ is also essential in the formation of the apoptosome along with other adapter proteins. The loss of trophic factors activates pro-apoptotic enzymes, causing the breakdown of mitochondria.

Supplementation

Because of its ability to transfer electrons and therefore act as an antioxidant, Coenzyme Q has become a valued dietary supplement.

Young people are able to make Q₁₀ from the lower numbered ubiquinones such as Q₆ or Q₈. The sick and elderly may not be able to make enough, thus Q₁₀ becomes a vitamin later in life and in illness.

Supplementation of Coenzyme Q₁₀ has been found to have a beneficial effect on the condition of some sufferers of migraine headaches, and is a common component of the "mito cocktail" used to treat mitochondrial disorders and other metabolic disorders. It is also being investigated as a treatment for cancer, and as relief from cancer treatment side effects.

Recent studies have shown that the antioxidant properties of Coenzyme Q₁₀ benefit the body and the brain. Some of these studies indicate that Coenzyme Q₁₀ protects the brain from neurodegenerative disease such as Parkinsons and also from the damaging side effects of a transient ischemic attack (stroke) in the brain.

Another recent study shows a survival benefit after cardiac arrest if coenzyme Q₁₀ is administered in addition to commencing active cooling (to 32–34 degrees Celsius).

Synthesis and its inhibition by statins and beta blockers

The isoprene sidechain of Coenzyme Q₁₀ is synthesized from acetyl CoA by a series of enzymatic reactions, while the benzoquinone portion is synthesized from amino acids.

Coenzyme Q₁₀ shares a common biosynthetic pathway with cholesterol. Isopentenyl pyrophosphate and its isomer, dimethylallyl pyrophosphate, are linked alternatingly in polyprenyl chains, which are also called isoprenes. The 15-carbon isoprene chain is farnesyl pyrophosphate, which is a precursor to cholesterol, while the 50-carbon isoprene chain forms the sidechain of coenzyme Q₁₀.

The synthesis of an intermediary precursor of Coenzyme Q₁₀, mevalonate, is inhibited by some beta blockers, blood pressure lowering medication [1], and statins, a class of cholesterol lowering drugs [2]. Statins can reduce serum levels of coenzyme Q₁₀ by up to 40% [3]. Some research suggests the logical option of supplementation with coenzyme Q₁₀ as a routine adjunct to any treatment which may reduce endogenous production of coenzyme Q₁₀, based on a balance of likely benefit against very small risk. [4][5]