coenzyme Q10

Definition: Coenzyme Q10 (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10, CoQ, Q10, or simply Q) is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the isoprenyl chemical subunits.

This oil-soluble vitamin-like substance is present in most eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. Ninety-five percent of the human body’s energy is generated this way. Therefore, those organs with the highest energy requirements—such as the heart and the liver—have the highest CoQ10 concentrations.

Ubiquinone (coenzyme Q(10) or CoQ(10)) is a lipid-soluble component of virtually all cell membranes, where it functions as a mobile electron and proton carrier. CoQ (ubiquinone) serves as a redox carrier in the mitochondrial respiratory chain and is a lipid-soluble antioxidant.

Localization

CoQ is found in the membranes of many organelles. Since its primary function in cells is in generating energy, the highest concentration is found on the inner membrane of the mitochondrion. Some other organelles that contain CoQ10 include endoplasmic reticulum, peroxisomes, lysosomes, and vesicles.

Structure

This oil-soluble vitamin-like substance is present in most eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP.

Coenzyme Q10 (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10, CoQ, Q10, or Q) is a benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the isoprenyl chemical subunits.

Biosynthesis

The benzoquinone portion of Coenzyme Q10 is synthesized from tyrosine, whereas the isoprene sidechain is synthesized from acetyl-CoA through the mevalonate pathway (mevalonic acid pathway). The mevalonic acid pathway is also used for the first steps of cholesterol biosynthesis.

Antioxidant activity

Coenzyme Q10 is a fat-soluble antioxidant that is found in virtually all cell membranes, hence its alternative name "ubiquinone."

The antioxidant activity of vitamin E requires the CoQ10 to be available, to which vitamin E will pass on the unpaired electron (free radical) that it has scavenged.

CoQ10 also acts as an anti-oxidant independently, protecting against DNA damage and other forms of oxidative damage caused by the consumption of excess polyunsaturated fatty acids.

Lysosomes

It appears that Coenzyme Q10 might be involved in maintaining the proper pH of lysosomes, which are a digestive component of cells, as well.

Oxydative phosphorylation

Coenzyme Q10 is also an essential component of the mitochondria, playing a critical role in the formation of ATP, from carbohydrate and fatty acid metabolism.

CoQ(10)) is a vital lipophilic molecule that transfers electrons from mitochondrial respiratory chain complexes I and II to complex III.

COQ2

COQ2, or parahydroxybenzoate-polyprenyltransferase (EC 2.5.1.39), catalyzes one of the final reactions in the biosynthesis of CoQ, the prenylation of parahydroxybenzoate with an all-trans polyprenyl group.

Pathology

 CoQ(10) deficiency (MIM.607426)

• germline mutations in COQ2 (MIM.609825)
  • Leigh syndrome and nephrotic syndrome (17186472)

 CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures (18319072)

 ADCK3 is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency (18319074)

Muscle coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ(10) biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy.

Coenzyme Q(10) (CoQ(10)) plays a pivotal role in oxidative phosphorylation (OXPHOS) in that it distributes electrons between the various dehydrogenases and the cytochrome segments of the respiratory chain.

Primary coenzyme Q(10) deficiency represents a clinically heterogeneous condition suggestive of genetic heterogeneity, and several disease genes have been previously identified.

The CABC1 gene, also called COQ8 or ADCK3, is the human homolog of the yeast ABC1/COQ8 gene, one of the numerous genes involved in the ubiquinone biosynthesis pathway.

The exact function of the Abc1/Coq8 protein is as yet unknown, but this protein is classified as a putative protein kinase.

References

 Mollet J, Delahodde A, Serre V, Chretien D, Schlemmer D, Lombes A, Boddaert N, Desguerre I, de Lonlay P, de Baulny HO, Munnich A, Rötig A. CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. Am J Hum Genet. 2008 Mar;82(3):623-30. PMID: 18319072

 Lagier-Tourenne C, Tazir M, López LC, Quinzii CM, Assoum M, Drouot N, Busso C, Makri S, Ali-Pacha L, Benhassine T, Anheim M, Lynch DR, Thibault C, Plewniak F, Bianchetti L, Tranchant C, Poch O, DiMauro S, Mandel JL, Barros MH, Hirano M, Koenig M. ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. Am J Hum Genet. 2008 Mar;82(3):661-72. PMID: 18319074