Ubiquinol

Ubiquinol is an electron-rich (reduced) form of coenzyme Q10.

The natural ubiquinol form of coenzyme Q10 is 2,3-dimethoxy-5-methyl-6-poly prenyl-1,4-benzoquinol, where the polyprenylated side-chain is 9-10 units long in mammals. Coenzyme Q10 (CoQ10) exists in three redox states, fully oxidized (ubiquinone), partially reduced (semiquinone or ubisemiquinone), and fully reduced (ubiquinol). The redox functions of ubiquinol in cellular energy production and antioxidant protection are based on the ability to exchange two electrons in a redox cycle between ubiquinol (reduced) and the ubiquinone (oxidized) form.

Characteristics
Ubiquinol is a lipid-soluble benzoquinol that is found in all cellular systems and in nearly every cell, tissue, and organ in mammals. Ubiquinol is acquired through biosynthesis, supplementation, and, in small amounts, diet. Ubiquinol has an established role as an essential component of the electron transport chain transferring electrons resulting in ATP synthesis. In mammals, ATP production takes place predominantly in mitochondria and to a lesser extent in other organelles such as the Golgi apparatus or endoplasmic reticulum. The mitochondria typically produce nearly 95% of the energy required for cellular growth, development, and healthy metabolism. The antioxidant action of ubiquinol is now considered to be one of the most important functions in cellular systems.

Ubiquinol is the antioxidant form of CoQ10 and is essential for mitochondrial synthesis of energy. It is the only known lipid-soluble antioxidant that is endogenously synthesized, protecting biological membranes against lipid peroxidation as well as regenerating other antioxidants such as Vitamin C and Vitamin E.

Because humans can synthesize ubinquinol, it is not classed as a vitamin.

Bioavailability
It is well-established that CoQ10 is not well absorbed into the body, as has been published in many peer-reviewed scientific journals. Since the ubiquinol form has two additional hydrogens, it results in the conversion of two ketone groups into hydroxyl groups on the active portion of the molecule. This causes an increase in the polarity of the CoQ10 molecule and may be a significant factor behind the observed enhanced bioavailability of ubiquinol. Taken orally, ubiquinol exhibits greater bioavailability than ubiquinone.

However, there are authorities that dispute whether ubiquinol is more bioavailable in practice rather than in theory compared to CoQ10 supplements because those have their CoQ10 molecules dissolved in lipid micelles, which then deliver their cargo to the plasma membrane in the intestinal wall. There they dissolve via simple diffusion in the intestinal cells, then onto the lymphatic vessels, and then into the venous system. Since ubiquinol and CoQ10 are redox pairs and can and are rapidly inter-converted in the body, it is not clear that ubiqinol's more hydrophilic nature compared to CoQ10 is of practical significance.

Content in foods
In foods, there are varying amounts of ubiquinol. An analysis of a range of foods found ubiquinol to be present in 66 out of 70 items and accounted for 46% of the total coenzyme Q10 intake. The following chart is a sample of the results.

Molecular aspects
Ubiquinol is a benzoquinol and is the reduced product of ubiquinone also called coenzyme Q10. Its tail consists of 10 isoprene units.

The reduction of ubiquinone to ubiquinol occurs in Complexes I & II in the electron transfer chain. The Q cycle is a process that occurs in cytochrome b, a component of Complex III in the electron transport chain, and that converts ubiquinol to ubiquinone in a cyclic fashion. When ubiquinol binds to cytochrome b, the pKa of the phenolic group decreases so that the proton ionizes and the phenoxide anion is formed.

If the phenoxide oxygen is oxidized, the semiquinone is formed with the unpaired electron being located on the ring.

A page on Proteopedia, Complex III of Electron Transport Chain, contains rotatable 3-D structures of Complex III, which may be used to study the peptide structures of Complex III and the mechanism of the Q cycle.