BIOSYNTH Molecule of the Month: Ubiquitous Coenzyme Q10

Microbiology and organic fine biochemical CDMO and specialist supplier, BIOSYNTH AG, has more than 100, 000 substances and molecular entities in its product portfolio. Each of them has its own particular applications and story to tell.

Here is an example of the molecular entities that BIOSYNTH regularly features on its website every week. This month we are focusing on Ubiquitous Coenzyme Q10 (Ubiquinone) – one of the most hydrophobic molecules in living nature.

Ubiquinone: description

Coenzyme Q10, also known as ubiquinone, (Biosynth catalog number C-7060) is a fat-soluble substance that is ubiquitous in eukaryotic cellular membranes of animals and most bacteria. CoQ10 is present primarily in the mitochondria, where it plays important role in mechanism of ATP formation, responsible for generating 95% of the human body’s energy¹.

The highest CoQ10 concentrations are in the organs with highest energy requirements – heart, liver and kidney². CoQ also plays a central role in cellular bioenergetics and functions as an electron carrier in the mitochondrial electron transport chain (ETC) for ATP production. It also acts as a potent endogenous antioxidant in its reduced form that prevents lipid peroxidation, protein carbonylation and oxidative damage to DNA³.

Ubiquinone in history

The discovery of coenzyme Q has been presented as a simple accident but the real story is more complex, being the result of much investigation of compounds involved in the mechanism of biological energy conversion⁴.

CoQ10 was first isolated in 1957 from beef heart mitochondria by Dr. Frederick Crane of Wisconsin, U.S.A. During the same year in the UK, Professor Richard Alan Morton coincidentally defined the same compound as CoQ10 from deficient rat liver and introduced it as ubiquinone – denoting ‘the ubiquitous quinone’.

The following year, 1958, Professor Karl Folkers clarified the chemical structure of CoQ10 as 2,3 dimethoxy-5 methyl-6 decaprenyl benzoquinone allowing his team to synthesize ubiquinone and produce it by fermentation.

Peter Mitchell received the Nobel Prize in 1978 for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory, which includes the Proton motive role of CoQ10 in energy transfer systems⁵. Under the term ‘chemiosmosis’ we can understand the movement of ions across a semipermeable membrane, down their electrochemical gradient. Hydrogen ions (H+) move across this membrane during cellular respiration while ATP is generated.

The chemistry of CoQ

The chemical structure of CoQ10 includes 1,4-benzoquinone as a head group and an extraordinarily long polyisoprenoid lipid tail with 10 five carbon isoprene subunits, which makes it one of the most hydrophobic molecules in nature. Quinone head group makes it reduction–oxidation (redox) active. The redox activity of CoQ allows it to function as a cofactor for numerous enzymes, including those of the mitochondrial electron transport chain⁶. CoQ 10 exists in three redox states, fully oxidized (ubiquinon, CoQ), free-radical intermediate (semiquinone/ubisemiquinon, CoQH-) and reduced (ubiquinol, CoQH².

The transformation between these redox states allows to act as a two-electron carrier (quinone to quinol form) and a one-electron carrier (semiquinone to quinon or quinol form). The redox chemistry of CoQ also involves the protons movement which is part of the ‘Q-cycle’ that helps generate the proton motive force that drives ATP production via oxidative phosphorylation⁶.

Coenzyme Q in medicine

There are two major factors that lead to deficiency of CoQ10 in humans: reduced biosynthesis, and increased use by the body. Currently, most clinical centers measure CoQ10 levels in cultured skin fibroblasts, muscle biopsies, and blood mononuclear cells.

While CoQ10 is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of any medical condition, it is sold as a dietary supplement, regulated as a foodstuff.

There is some evidence that CoQ10 supplements reduced cardiovascular events versus placebo but evidence with respect to preventing heart disease in healthy patients is poor.

Research has also suggested some connections between Coenzyme Q and male fertility, with migraine headaches and with muscle breakdown associated with use of statin medications.

References

1. Ernster, L., Dallner, G. (1995) Biochim Biophys Acta. 1271 (1), 195–204: Biochemical, physiological and medical aspects of ubiquinone function.
2. Shindo. Y., Witt. E., Han. D., Epstein. W., Packer. L. (1994) J Invest Dermatol. 102 (1), 122–124: Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin.
3. Pandey, R, , Riley, Ch. L., Mills, E. M., Tiziani, S. (2018) Anal Chim Acta. 1011, 68-76: Highly sensitive and selective determination of redox states ofcoenzymes Q9 and Q10 in mice tissues: Application of orbitrap mass spectrometry.
4. Crane, F. L. (2007) Mitochondrion: Discovery of ubiquinone (coenzyme Q) and an overview of function.
5. Langsjoen, P.H. (2008). Introduction to Coenzyme Q10. https://www.researchgate.net/publication/239772517_INTRODUCTION_TO_COENZYME_Q10
6. Stefely, J. A., Pagliarini, D. J. (2017). Trends Biochem Sci, 42(10), 824–843: Biochemistry of Mitochondrial Coenzyme Q Biosynthesis.

Resources

Click on BIOSYNTH Molecule of the Month: Ubiquinone for more information.
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Click on Coenzyme Q10: C-7060 for product information.