Ubiquinone vitamin

Can mitochondrial diseases be treated Attempts are being made to improve the function of impaired mitochondria by adding large amounts of ubiquinone, vitamin K, thiamin, riboflavin, and succinate to the diet.6 One report suggests that mitochondrial decay during aging can be reversed by administration of N-acetylcarnitine.k... 

Coenzyme QIO (ubiquinone) Vitamin K (menaquinone) Acetyl-CoA, Tyrosine Nutritional... 

Besides these enzyme substrates, a number of biological molecules are likely to give rise to fairly stable and hence observable free radicals. The more important of these are the quinonoid molecules, particularly vitamin Q quinone (ubiquinone), vitamin E quinone, vitamins K, Ks and vitamin E quinone, the flavins and flavoproteins and the important neurochemicals dopa, dopamine, and closely related phenolic and quinonoid molecules. In many of these cases, the generation of free radicals from these molecules should occur in vivo, but as yet only a few radicals such as the ascorbyl radical and the bacteriochlorophyll radical have been directly identified in intact systems. Free radicals from melanins (polymers from dopaquinone) have been demonstrated both in vivo and in vitro, but these radicals are so stable that it has not yet been possible to identify a biological role for the radicals per se. 

Isoprenylated Quinones.—A book has been published dealing with biomedical and clinical aspects of coenzyme Q [ubiquinone (203)]. Other reviews have appeared on the chemistry and biochemistry of ubiquinone,vitamin K [phyl-loquinone (204) and menaquinone (205)], and plastoquinone (206) and on the chemical methods for prenylation of quinones. ... 

Once the nature of the unsaturation in the C17 chain was established, we considered if this structural feature had an active role in function or could we say nature has just been too lazy to reduce these double bonds to give a saturated polyisoprenoid group. Possibly related in function are the similarly unsaturated, though frequently much longer, isoprenoid chains of ubiquinones, vitamin K s, and related compounds, substances also implicated in electron-transfer and/or oxidative phosphorylation processes. Thus, the C17 group in heme A may be directly related to either electron transfer or coupling of phosphorylation in the oxidase. 

Mukai, K, Itoh, S., and Morimoto, H., Stopped-flow kinetic study of vitamin E regeneration reaction with biological hydroquinones (reduced forms of ubiquinone, vitamin K, and tocopherolquinone) in solution, J Biol Chem 267 (31), 22211- 22 2, 1992. 

C7H,o05, Mr 174.15. needles, D. 1.6, mp. 178-180°C, [a]g -157° (H2O), pKg4.15 (14.1 °C), soluble in water. S. is a widely distributed component of plants and occurs especially in fruits of the star anise (lllicium anisatum, syn. /. religiosum, Illiciaceae Japanese shi-kimi-no-ki). S. is a key intermediate of the so-called shikimic acid pathway which includes the biosynthesis of the aromatic amino acids phenylalanine, tyrosine, and tryptophan. These, in turn, are precursors of numerous alkaloids, flavonoids, and lignans, as well as 4-amino- and 4-hydroxybenzoic acid, gallic acid, tetrahydrofolic acid, ubiquinones, vitamin K, and nicotinic acid. The synthetic racemate melts at 191-192 °C. 

Because shikimic acid does not enter into mammalian metabolism, its synthesis and use are clear targets at which to aim selective toxicity. In bacteria, shikimic acid arises by cyclization of the carbohydrate 3-deoxy-2-oxo-D- mAzVzoheptulosonic acid 7-phosphate, which is formed by the condensation of erythrose 4-phosphate and phosphoenolpyruvic acid. Shikimic acid undergoes biosynthesis to chorismic acid (4.55) which is the enolpyruvic ether of raw5-3,4-dihydroxy cyclohexa-1,5-diene-1-carboxylic acid. As its name indicates, this acid sits at a metabolic fork, the branches of which lead to prephenic acid, to phenylalanine (and hence to tyrosine), to anthranilic acid (and hence tryptophan), to ubiquinone, vitamin K, and/ -aminobenzoic acid (and hence folic acid). 

Vitamin B2 phosphate sodium. See Riboflavin-5 -phosphate sodium Vitamin PP. See Niacinamide Vitamin A propionate. See Retinyl propionate Vitamin Q. See Ubiquinone Vitamin C sodium salt. See Sodium ascorbate Vitamin E succinate. See Tocopheryl succinate Vitamin Be tripalmitate. See Pyridoxine tripalmitate... 

It has been found that a cytochrome-c-reductase preparation, deactivated by extraction with isodctane, can be reactivated by addition of vitamine E and derivatives (Nason and Lehman, 1956). As described in Section VII, 2, other substances with an isoprene-like side chain, such as ubiquinone, vitamin Ki, and K were found to be active. Additionally it could be shown that this side chain— and not the redox system—is responsible for the reactivation (Weber el at., 1958a,b). 

FIGURE 8.18 Dolichol phosphate is an initiation point for the synthesis of carbohydrate polymers in animals. The analogous alcohol in bacterial systems, undecaprenol, also known as bactoprenol, consists of 11 isoprene units. Undecaprenyl phosphate delivers sugars from the cytoplasm for the synthesis of cell wall components such as peptidoglycans, lipopolysaccharides, and glycoproteins. Polyprenyl compounds also serve as the side chains of vitamin K, the ubiquinones, plastoquinones, and tocopherols (such as vitamin E). 

Ubiquinone or Q (coenjyme Q) (Figure 12-5) finks the flavoproteins to cytochrome h, the member of the cytochrome chain of lowest redox potential. Q exists in the oxidized quinone or reduced quinol form under aerobic or anaerobic conditions, respectively. The structure of Q is very similar to that of vitamin K and vitamin E (Chapter 45) and of plastoquinone, found in chloroplasts. Q acts as a mobile component of the respiratory chain that collects reducing equivalents from the more fixed flavoprotein complexes and passes them on to the cytochromes. 

Meganathan, R., Biosynthesis of menaquinone (vitamin Kj) and ubiquinone (coenzyme Q) a perspective on enzymatic mechanism. Vitamins Hormones, 61, 173, 2001. 

A large number of nonenzymatic compounds, including tocopherols, caroti-noids, vitamins C and D, steroids, ubiquinones, thiols, uric acid, bilirubin, ino-sine, taurine, pyruvate, CRP, and so on, demonstrate qualitative antioxidant properties under experimental conditions. However, the quantitative relevance of most findings remains unclear. 

The effects of antioxidants on protein oxidation were also studied in animal experiments. Barja et al. [73] demonstrated that feeding guinea pigs with vitamin C decreased endogenous protein oxidative damage in the liver. Administration of the mixture of antioxidants containing Trolox C, ascorbic palmitate, acetylcysteine, (3-carotene, ubiquinones 9 and 10, and (+)-catechin in addition to vitamin E and selenium to rats inhibited heme protein oxidation of kidney homogenates more efficiently than vitamin E + selenium [74]. 

The efficiency of vitamin E in the suppression of free radical-mediated damage induced by iron overload has been studied in animals and humans. Galleano and Puntarulo [46] showed that iron overload increased lipid and protein peroxidation in rat liver. Vitamin E supplementation successfully suppressed these effects and led to an increase in a-tocopherol, ubiquinone-9, and ubiquinone-10 contents in liver. Important results were obtained by Roob et al. [47] who found that vitamin E supplementation attenuated lipid peroxidation (measured as plasma MDA and plasma lipid peroxides) in patients on hemodialysis after receiving iron hydroxide sucrose complex intravenously during hemodialysis session. These findings support the proposal that iron overload enhances free radical-mediated damage in humans. 

Contemporary interest in ubiquinones is explained by their potential antioxidant activity and the possibility of using these nontoxic natural compounds as pharmaceutical agents. But it should be noted that ubiquinones are not vitamins and that they are synthesized in humans. Taking into account a high level of ubiquinones in mitochondria, the effective supplementation of ubiquinones to fight against free radical-mediated damage seems to be a hard task. 

This mechanism is now considered to be of importance for the protection of LDL against oxidation stress, Chapter 25.) The antioxidant effect of ubiquinones on lipid peroxidation was first shown in 1980 [237]. In 1987 Solaini et al. [238] showed that the depletion of beef heart mitochondria from ubiquinone enhanced the iron adriamycin-initiated lipid peroxidation whereas the reincorporation of ubiquinone in mitochondria depressed lipid peroxidation. It was concluded that ubiquinone is able to protect mitochondria against the prooxidant effect of adriamycin. Inhibition of in vitro and in vivo liposomal, microsomal, and mitochondrial lipid peroxidation has also been shown in studies by Beyer [239] and Frei et al. [240]. Later on, it was suggested that ubihydroquinones inhibit lipid peroxidation only in cooperation with vitamin E [241]. However, simultaneous presence of ubihydroquinone and vitamin E apparently is not always necessary [242], although the synergistic interaction of these antioxidants may take place (see below). It has been shown that the enzymatic reduction of ubiquinones to ubihydroquinones is catalyzed by NADH-dependent plasma membrane reductase and NADPH-dependent cytosolic ubiquinone reductase [243,244]. 

In the case of ubiquinones we have already considered the ability of quinones to react with superoxide and other free radicals. Naphthoquinones, vitamin K and its derivatives, especially menadione, are the well known producers of superoxide through redox cycling with dioxygen. However, in 1985, Canfield et al. [254] have shown that vitamin K quinone reduced the oxidation of linoleic acid while vitamin K hydroquinone stimulated lipid peroxidation. Surprisingly, later on, conflicting results were reported by Vervoort et al. [255] who found that only hydroquinones of vitamin K and its analogs inhibited microsomal lipid peroxidation. 

The reaction has been applied for the synthesis of polyprenyl quinol natural product ubiquinone and vitamin K. 

Special tasks. Some lipids have adopted special roles in the body. Steroids, eicosanoids, and some metabolites of phospholipids have signaling functions. They serve as hormones, mediators, and second messengers (see p.370). Other lipids form anchors to attach proteins to membranes (see p.214). The lipids also produce cofactors for enzymatic reactions—e.g., vitamin K (see p.52) and ubiquinone (see p.l04). The carotenoid retinal, a light-sensitive lipid, is of central importance in the process of vision (see p.358). 

Isoprene chains are sometimes used as lipid anchors to fix molecules to membranes (see p. 214). Chlorophyll has a phytyl residue (1 = 4) as a lipid anchor. Coenzymes with isoprenoid anchors of various lengths include ubiquinone (coenzyme Q 1 = 6-10), plastoqui-none (1 = 9), and menaquinone (vitamin K 1 = 4-6). Proteins can also be anchored to membranes by isoprenylation. 

The role of ubiquinone (coenzyme Q, 4) in transferring reducing equivalents in the respiratory chain is discussed on p. 140. During reduction, the quinone is converted into the hydroquinone (ubiquinol). The isoprenoid side chain of ubiquinone can have various lengths. It holds the molecule in the membrane, where it is freely mobile. Similar coenzymes are also found in photosynthesis (plastoquinone see p. 132). Vitamins E and K (see p. 52) also belong to the quinone/hydroquinone systems. 

Polyprenyis vitamin K group (plants and Bact.) and vitamin E (Ang.) and ubiquinones (mitochondria). 

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