Coenzyme Q10 (CoQ10, also called ubiquinone because it is ubiquitous in all living organisms) is a lipid-soluble quinone molecule that is an essential component of the mitochondrial electron transport chain — it is the mobile electron carrier that shuttles electrons between the complex I (NADH dehydrogenase) and the complex II (succinate dehydrogenase) on one side and the complex III (cytochrome bc1 complex) on the other side of the chain. CoQ10 is unique among the components of the electron transport chain in that it is synthesised endogenously in the body (by the mevalonate pathway, which is the same pathway that is used for the cholesterol synthesis) — all of the other components of the electron transport chain (the iron-sulfur clusters, the flavins, the cytochromes) are derived from the dietary sources or from the cofactor synthesis pathways. The CoQ10 molecule consists of a quinone ring system (which is the redox-active component that accepts and donates electrons) and of a polyisoprene tail (which consists of 10 isoprene units in the CoQ10 form and which gives the molecule its lipid solubility and its ability to diffuse in the inner mitochondrial membrane). When CoQ10 is reduced (to the ubiquinol form), it carries two electrons and two protons; when it is oxidised (to the ubiquinone form), it carries no electrons — and this redox cycling is the basis of its function as the mobile electron carrier in the electron transport chain.
The CoQ10 and the ATP Synthesis
The electron transport chain is the series of enzyme complexes (complex I, II, III, IV, V) that are embedded in the inner mitochondrial membrane and that couple the oxidation of the NADH and the FADH2 to the pumping of the protons across the inner membrane and to the synthesis of the ATP. The electrons from the NADH enter the chain at the level of the complex I (for the FADH2, they enter at the level of the complex II), and they flow down the chain through the CoQ10 (which shuttles them from complex I/II to the complex III) and through the cytochrome c (which shuttles them from the complex III to the complex IV). As the electrons flow down the chain, the energy that is released is used to pump the protons from the mitochondrial matrix to the intermembrane space, creating the electrochemical gradient (the proton motive force) that drives the synthesis of the ATP by the ATP synthase (complex V). This oxidative phosphorylation is the primary mechanism by which the cell generates the ATP from the energy that is stored in the NADH and the FADH2, and it is dependent on the CoQ10 for the efficient transfer of the electrons from the complex I and the complex II to the complex III.
The clinical importance of the CoQ10 for the ATP synthesis is underscored by the observation that the CoQ10 deficiency produces a characteristic reduction in the cellular ATP levels, which is the diagnostic marker of the CoQ10 deficiency. The CoQ10 deficiency can be primary (caused by genetic mutations in the CoQ10 synthesis pathway) or secondary (caused by the statin therapy, by the ageing, or by the chronic diseases that impair the CoQ10 synthesis), and it produces a clinical syndrome that includes the fatigue, the muscle weakness, the exercise intolerance, the cardiac failure, and the encephalopathy — all of which are the direct result of the impaired ATP synthesis and the resulting energy failure.
CoQ10 and the Cardiac Function
The heart is one of the organs that is most dependent on the continuous supply of the ATP from the mitochondrial oxidative phosphorylation — it has a very high energy demand (consuming approximately 6-8kg of ATP per day in the resting adult) and it has a limited capacity for the anaerobic metabolism (because the cardiac muscle has few mitochondria relative to its mass). The CoQ10 is therefore particularly important for the cardiac function — it is required for the electron transport chain in the cardiac mitochondria and for the maintenance of the cardiac contractile function. The CoQ10 has been studied extensively as a treatment for the congestive heart failure (CHF) — multiple meta-analyses have demonstrated that CoQ10 supplementation at 100-300mg daily improves the exercise tolerance, reduces the symptoms of the CHF (dyspnoea, fatigue, peripheral oedema), reduces the hospitalisation rate, and reduces the mortality rate in patients with the CHF. The proposed mechanism of this benefit involves the restoration of the electron transport chain activity in the cardiac mitochondria, the improvement of the cardiac contractile efficiency, and the reduction of the oxidative stress in the myocardium.
Practical Application
For general CoQ10 supplementation, the evidence-based approach is to supplement with 100-300mg of CoQ10 daily (as the ubiquinol form, which is the reduced and more bioavailable form, especially for older adults who may have impaired conversion of the ubiquinone to the ubiquinol). The CoQ10 is fat-soluble and should be taken with a fat-containing meal for optimal absorption. The CoQ10 is generally well-tolerated with no significant adverse effects at doses up to 300mg daily, though it may interact with the warfarin (reducing the INR) and with the blood pressure medications (enhancing their effect). For comprehensive mitochondrial and cardiovascular support, CoQ10 pairs well with the L-carnitine (which is required for the transport of the fatty acids into the mitochondria), with the alpha-lipoic acid (which is a powerful antioxidant that regenerates vitamin E and which has complementary effects on the mitochondrial energy metabolism), with the magnesium (which is required for the function of the ATP synthase and for the activation of many of the cofactor-dependent enzymes), and with the D-ribose (which is a pentose sugar that is used for the synthesis of the nucleotides and of the ATP and which has been shown to improve the cardiac function in patients with the CHF).
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