Coenzyme Q – Biosynthesis and functions
Introduction
Coenzyme Q (CoQ) is present in every membrane of all cells in the body [1]. Under normal physiological conditions all cells biosynthesize functionally sufficient amounts of this lipid. Thus, in contrast to cholesterol, no redistribution via or uptake from the circulation is required. The liver does release a certain amount of newly synthesized CoQ that associates with VLDL and provides circulating lipoproteins with an antioxidant defense, but this pool is not redistributed to other organs. Consequently, measurement of blood levels of CoQ provides only limited information concerning its actual levels in organs and cells. Under various conditions attenuated synthesis results in reductions in these levels and disturbance of normal functions. Since dietary uptake of CoQ is limited to only a few percent, numerous efforts are continuously directed towards the preparations of forms that are taken up more efficiently or substitutes with functional properties similar to those of CoQ and which are taken up into the circulation and cells more extensively.
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Functions of CoQ
Following its isolation and characterization in 1955, CoQ was originally shown to be a necessary component of the mitochondrial respiratory chain two years later. It functions as an electron carrier from complex I and II to complex III and, according to Mitchell’s protonmotive Q cycle, production of ubisemiquinone accounts for the energy conservation occurring at coupling site 2 of the respiratory chain [2].
Today, several other important functions are also associated with this lipid.
- 1.
The plasma
The mevalonate pathway
Starting from acetyl-CoA, the series of reactions that comprise the mevalonate pathway produces farnesyl-PP, the precursor for cholesterol, CoQ, dolichol and isoprenylated proteins [12] (Fig. 1). In addition, the intermediary isopentenyl-PP is utilized for the synthesis of dolichol and the isoprenoid side-chain of CoQ. Since the initial sequence of reactions leading to all end-products of the mevalonate pathway is identical, it might be expected that synthesis of these various lipids is
Up-regulation of CoQ synthesis
In the case of most metabolic pathways a large number of endogenous metabolites play regulatory rolls. Likewise, production of cholesterol, the main product of the mevalonate pathway, is regulated by several different substances, including oxysterols, squalene oxide, farnesol and its derivatives, geranylgeraniol and prenyl phosphates. It thus seems likely that endogenous compounds also regulate the biosynthesis of CoQ.
In HepG2 cells epoxidated derivatives of certain all-trans polyisoprenoids,
Deficiencies in CoQ synthesis
Some cases of CoQ deficiency in humans result from inactivating mutations in the genes encoding the relevant biosynthetic proteins. Depending on the localization and extent of the defect, the clinical symptoms vary greatly. The brain, cerebellum, muscles and/or kidney may be involved, usually resulting in complex disease patterns [22].
A number of the mutations are characterized, referred to as primary types, directly affect the proteins involved in the biosynthesis of the CoQ [23] (Table 1).
Regulation of tissue levels of CoQ
The actual level of CoQ is determined by a coordinated balance between the synthetic and catabolic enzymes, which are both expressed in all tissues. This lipid is rapidly broken down, as reflected in its short half-life, T1/2, of 49–125 h in various tissues and the initial steps in this degradation involve ω-oxidation and subsequent β-oxidation of the side-chain [25]. The primary breakdown product detected in tissues, the urine and feces contains an intact, fully substituted ring, a short
Acknowledgments
The authors’ research is supported financially by the Family Erling-Persson Foundation and the Swedish Research Council.
References (36)
- et al.
Metabolism and function of coenzyme Q
Biochim. Biophys. Acta
(2004) Protonmotive redox mechanism of the cytochrome b–c1 complex in the respiratory chain: protonmotive ubiquinone cycle
FEBS Lett.
(1975)- et al.
Coenzyme q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property
J. Biol. Chem.
(2003) - et al.
beta2-Integrin and lipid modifications indicate a non-antioxidant mechanism for the anti-atherogenic effect of dietary coenzyme Q10
Biochem. Biophys. Res. Commun.
(2002) - et al.
The antioxidant role of coenzyme Q
Mitochondrion
(2007) - et al.
Rates of cholesterol, ubiquinone, dolichol and dolichyl-P biosynthesis in rat brain slices
FEBS Lett.
(1990) - et al.
Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins
Biochim. Biophys. Acta
(1994) - et al.
Endogenous synthesis of coenzyme Q in eukaryotes
Mitochondrion
(2007) - et al.
Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth
J. Lipid Res.
(1980) - et al.
Effects of mevinolin treatment on tissue dolichol and ubiquinone levels in the rat
Biochim. Biophys. Acta
(1992)
Effect of squalestatin 1 on the biosynthesis of the mevalonate pathway lipids
Biochim. Biophys. Acta
Squalene synthase inhibition alters metabolism of nonsterols in rat liver
Biochim. Biophys. Acta
Polyisoprenoid epoxides stimulate the biosynthesis of coenzyme Q and inhibit cholesterol synthesis
J. Biol. Chem.
Infantile and pediatric quinone deficiency diseases
Mitochondrion
Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency
Lancet
Half-life of ubiquinone-9 in rat tissues
FEBS Lett.
Distribution and breakdown of labeled coenzyme Q10 in rat
Free Radic. Biol. Med.
Nonaprenyl-4-hydroxybenzoate transferase, an enzyme involved in ubiquinone biosynthesis, in the endoplasmic reticulum–Golgi system of rat liver
J. Biol. Chem.
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