The antioxidant role of coenzyme Q

doi:10.1016/j.mito.2007.02.006

Mitochondrion

Volume 7, Supplement, June 2007, Pages S41-S50

https://doi.org/10.1016/j.mito.2007.02.006 Get rights and content

Abstract

A number of functions for coenzyme Q (CoQ) have been established during the years but its role as an effective antioxidant of the cellular membranes remains of dominating interest. This compound is our only endogenously synthesized lipid soluble antioxidant, present in all membranes and exceeding both in amount and efficiency that of other antioxidants. The protective effect is extended to lipids, proteins and DNA mainly because of its close localization to the oxidative events and the effective regeneration by continuous reduction at all locations. Its biosynthesis is influenced by nuclear receptors which may give the possibility, in the future, by using agonists or antagonists, of reestablishing the normal level in deficiencies caused by genetic mutations, aging or cardiomyopathy. An increase in CoQ concentration in specific cellular compartments in the presence of various types of oxidative stress appears to be of considerable interest.

Introduction

Oxygen present in the atmosphere is the basis of our life on earth. Paradoxical is the fact that it is a very toxic substance under a number of conditions. Derivatives, such as hydroxyl and superoxide radicals, hydrogen peroxide and singlet oxygen may be formed and are called reactive oxygen species (ROS). These compounds appear not only in diseases but also under normal physiological conditions and interact with basic tissue components with consequences of disturbed function. Various types of antioxidant defense systems are, however, available in all organisms for limitation and elimination of these unwanted species.

Increased levels of free radicals are counteracted by antioxidants, but low concentrations of these compounds participate in redox signaling and by regulating gene expression they influence among others the activation and synthesis of antioxidants and other enzymes (Sen and Packer, 1996). Cellular effects elicited by minor amounts of ROS products, such as the generation of growth factors, production of hormones and modulation of tyrosine phosphatase are of great importance in cell cycle regulation, proliferation, differentiation and survival (Martindale and Holbrook, 2002). These radicals also participate in the regulation of immune response through the T cells by suppressing autoreactivity and development of arthritis (Gelderman et al., 2006).

Section snippets

ROS formation

In a number of enzymatic processes oxygen is reduced by one electron transfer to the superoxide radical $O_{2}^{-}$ , hydrogen peroxide (H₂O₂) and hydroxyl radical (OH) (Cadenas et al., 1992). The enzymes which belong to this group are the monoamine oxidase in mitochondrial outer membranes, acyl-CoA oxidase of peroxisomes, xanthine oxidase, microsomal NADH-cytochrome b₅ and cytochrome-P450 reductases and the NADPH oxidase in neutrophils. Mitochondrial electron transport is accounted for two-thirds of

Lipid, protein and DNA oxidation

Excess of free radicals affects the basic cellular constituents such as lipids, proteins and DNA and the damage caused is known as oxidative stress. Lipid peroxidation is a process studied in great detail and the mechanism is well characterized (Ernster, 1993). During the first phase, called initiation, an abstraction of a hydrogen atom from a methylene group of a fatty acid occurs presupposing that it has several double bonds (Fig. 1). This gives a carbon-centered alkyl radical (L) and

Distribution of CoQ

Biosynthesis of CoQ occurs in all tissues and cells in the animal organism and the lipid is present in all membranes (Turunen et al., 2004). The amount is specific for the membrane type which is apparent in comparison with the distribution of other membrane lipids (Table 1). The CoQ amount related to dolichol, cholesterol or α-tocopherol amounts is highly variable and is a consequence of the functional specialization associated with the individual membranes. From the point of view of

Antioxidant action of CoQ

There are four major groups of naturally occurring lipid soluble antioxidants, carotenoids, tocopherols, estrogens and coenzyme Q. The individual components in the groups vary greatly concerning distribution and effectiveness, e.g., in the group of vitamin E eight major compounds are operating, α-, β-, γ- and δ-tocopherols and -tocotrienols but in humans only α-tocopherol is effective as antioxidant. The liver contains a transfer protein that is specific for α-tocopherol and this compound is

Enzymatic reduction

The amount of CoQ varies greatly in different tissues and subcellular organelles. In most cases the major part of the lipid is found in a reduced form. In spite of the fact that during storage and isolation some autooxidation is expected, in most human autopsy material the proportion of the reduced form is the dominant species (Table 4). Autopsy material is probably not ideal for measurement of the steady state reduction of CoQ, however, the values are comparable with the values obtained on

The antioxidant role in blood

In plasma the CoQ content in very low density, low density and high density lipoproteins is 1.2, 1.0 and 0.1 nmol/mg protein, respectively. The amounts are increased after dietary administration of the lipid to 3.2, 3.5 and 0.3 nmol/mg protein, respectively (Mohr et al., 1992). In all tissues the CoQ content is 6–10 times higher than that of vitamin E but in the blood its amount is only one-tenth of the main blood lipid soluble antioxidant, vitamin E. However, the very efficient reductive

CoQ as prooxidant

It is known that electron leakage occurs during mitochondrial respiration leading to superoxide radicals and H₂O₂. Findings such as that respiration gives ubisemiquinone which reacts with oxygen, that antimycin increase electron leakage and that extraction of CoQ from mitochondria inhibits H₂O₂ production, leads to a plausible assumption that CoQ can promote oxidation in mitochondria. Part of the ubisemiquinone is produced at the outer section of the membrane, bordering the aqueous phase. This

Stability and oxidative stress

There are several indications that under various pathological conditions CoQ in membranes is structurally modified and subjected to breakdown. The importance of these modifications is that the products may act as signaling molecules and influence a number of metabolic and synthetic pathways. The high degree of reduction of this lipid is not only a functional requirement but it is also a necessity for protection against oxidative damages (Forsmark-Andree et al., 1997). Submitochondrial particles

Induction of biosynthesis

Lowered CoQ content in tissues may appear as a primary deficiency for genetic reasons, caused by aging or by damage of the biosynthetic system in diseases and toxic injury. The decrease may be extensive or mild and probably much more common than assumed today. In the case of cholesterol, the liver produces the lipid to supply other organs and one-third of the required daily amount is taken up from the diet. Consequently, cholesterol level in the blood is a mirror and diagnostic marker for the

Conclusions

The high efficiency of CoQ as a lipid soluble antioxidant is established because of its localization, effective reactivation and relatively high concentration. Additionally, it appears both to inhibit the initiation part and interfere with the propagation step of lipid and protein oxidation, a property not apparent in the case of other antioxidants. All tissues and cells are capable of synthesis of this lipid to such an extent that ensures sufficient local concentration without redistribution

Acknowledgements

The authors work is supported by the Swedish Research Council, the Family Erling-Persson Foundation and the European Community (CT-2004-005151).

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The antioxidant role of coenzyme Q

Abstract

Introduction

Section snippets

ROS formation

Lipid, protein and DNA oxidation

Distribution of CoQ

Antioxidant action of CoQ

Enzymatic reduction

The antioxidant role in blood

CoQ as prooxidant

Stability and oxidative stress

Induction of biosynthesis

Conclusions

Acknowledgements

Arch. Biochem. Biophys.

Chem. Biol. Interact.

Free Radic. Biol. Med.

J. Mol. Biol.

Methods Enzymol.

J. Lipid Res.

Biochim. Biophys. Acta

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Arch. Biochem. Biophys.

FEBS Lett.

FEBS Lett.

Biochim. Biophys. Acta

FEBS Lett.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Free Radic. Biol. Med.

Biochem. Biophys. Res. Commun.

Free Radic. Biol. Med.

Biochem. Biophys. Res. Commun.

Am. J. Clin. Nutr.

Biochem. Pharmacol.

Methods Enzymol.

FEBS Lett.

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Biochim. Biophys. Acta

J. Mol. Biol.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Biochim. Biophys. Acta

Am. J. Clin. Nutr.

Free Radic. Biol. Med.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.