K2 and Ubiquinone

Vitamin K2 (65) and Ubiquinone Q-8 (66). To help define the biological origin of the ring methyl groups in vitamin Kj (65) and ubiquinone Q-8 (6Q, a 

Further confirmation for a deuteriated methyl group in vitamin K2 was achieved by n.m.r. spectroscopy. The signal for the unsaturated C-methyl group was absent at 2.17. This indicates a very high incorporation yield of labelled precursors in the methionine auxotroph. 

Similar results were found with the deuteriated ubiquinone Q-8 (66), which showed a base peak in the mass spectrum at m/e 244, compared with m/e 235 for the unlabelled material. This fragment ion for the quinone is similar to a or o. The molecular ion was at m/e 735 for the deuteriated material, compared with m/e 726 for the unlabelled quinone. Intensity comparisons showed an 

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MeganathanR (2001) Biosynthesis ofmenaquinone (vitamin K2) and ubiquinone (coenzyme Q) a perspective on enzymatic mechanisms. Vitamins and Hormones 173-218. 

Biosynthesis of menaquinone (vitamin K2) and ubiquinone (coenzyme Q) 01MI12. 

Meganathan R (1996) Biosynthesis of the isoprenoid quinones menaquinone (vitamin K2) and ubiquinone (coenzyme Q). In Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE (eds) Escherichia coli and Salmonella typhimurium Cellular and Molecular Biology. Vol 1. ASM, Washington DC, p 642... 

R. Meganathan 0. Kwon, Biosynthesis ot Menaquinone (Vitamin K2) and Ubiquinone (Coenzyme Q). In EcoSaZ-Escherichia coll and Salmonella Cellular and Molecular Biology A. Bock, R. Curtiss, III, J. B. Kaper, P. D. Karp, F. C. Neidhardt, T. Nystrom,... 

MK biosynthesis by the OSB pathway has been elucidated on the basis of isotopic tracer experiments, isolation of mutants blocked in the various steps, isolation and identification of intermediates accumulated by the mutants, and by enzyme assays. Early isotopic tracer experiments with various bacteria established that methionine and prenyl PPi contribute to the methyl and prenyl substituents of the naphthoquinone. The early isotopic tracer studies and other work have been reviewed by Bentley and Meganathan. " In 1964, Cox and Gibson observed that [G- " C] shikimate was incorporated into both MK and ubiquinone by E. coli, thus providing the first evidence for the involvement of the shikimate pathway." Chemical degradation of the labeled isolated menaquinone (MK-8) showed that essentially all of the radioactivity was retained in the phthalic anhydride. It was concluded that the benzene ring of the naphthoquinone (sic) portion of vitamin K2 arises from shikimate in E. coli The authors further suggested that shikimate was first converted to chorismate before incorporation into MK. A more complete chemical degradation of the MK derived from... 

Argentation TLC (on silver nitrate-impregnated silica gel plates) and hexane-ethyl acetate-diisopropyl ether (2 2 1, v/v/v) as mobile phase were used to separate vitamins Ki, K2, K3, ubiquinone-6, ubiquinone-9, and ubiquinone-10 (Rp values 0.71, 0.63, 0.57, 0.42, 0.21, and 0.28, respectively). ° ... 

For metabolic activity the polyisoprene side chain, present in the vitamin Kx and Kj molecules, seems to be necessary. Considering the fact that vitamin K2 compounds and ubiquinones with side chains of different lengths occur in nature, it would be interesting to find out whether this variation is correlated with differences in their natural function. Some evidence of such correlation has already been found in both in vivo and in vitro tests. 

Reaction centers of purple bacteria typically contain three polypeptides, four molecules of bacteriochlorophyll, two bacteriopheophytins, two quinones, and one nonheme iron atom. In some bacterial species, both quinones are ubiquinone. In others, one of the quinones is menaquinone (vitamin K2), a naphthoquinone that resembles ubiquinone in having a long side chain (fig. 15.10). Reaction centers of some species, such as Rhodopseudomonas viridis, also have a cytochrome subunit with four c-type hemes. 

The structures of ubiquinone, menaquinone (vitamin K2), plastoquinone, and phylloquinone (vitamin K ). Purple photosynthetic bacteria contain ubiquinone, menaquinone, or both, depending on the bacterial species chloroplasts contain plastoquinone and phylloquinone. 

There are different physiological forms known as vitamins K, namely vitamin Kj (phylloquinone, phytonadi-one) and vitamin K2 (farnoquinone). There are active anologs and related compounds knows as vitamins K, namely menadiol diphosphate, menadione (vitamin K3 ), menadione bisulfite, phthiocol, synkayvite, menadiol (vitamin K4), menaquinone-n (MK-n), ubiquinone (Q-n), and plastoquinone (PQ-n) [3]. 

Ubiquinone (UQ), also known as coenzyme Q, has a benzoquinone structure with a long side chain. The name ubiquinone is for the ubiquitous nature of the quinone. Some bacteria also contain menaquinone (vitamin K2), either in addition to ubiquinone or in place of it. For instance, the reaction center of Rhodopseudomonas viridis contains one ubiquinone and one menaquinone, while in some other bacterial reaction centers both quinones are ubiquinones. Menaquinone has a naphthoquinone structure with a long isoprenoid side chain. The long hydrocarbon side chains in ubiquinone and menaquinone render a high degree of hydrophobicity to these molecules. 

Vitamins and K2 exist in nature and are essential to the animal for their effect on the blood-clotting mechanism. While 2-methylnaphthoquinone itself and its related derivatives having isoprenoid side chains in position 3 also promote blood coagulation in varying degrees, coenzyme Q10 shows no activity in the blood-coagulating mechanism. Coenzyme Q10, also called ubiquinone because of its ubiquitous occurrence in animal tissues, is important in its own right, since it plays an essential role in oxidative phosphorylation. As in the case of the vitamin K series, the size of the isoprenoid side chain does not appear to be critical with respect to the oxidative phosphorylation activity of the coenzyme Q series. 

Since trimethylbenzoquinone is not converted into 2 , it appears that the complete side chain of a-tocopherol is not removed before building up the Cso side chain. In this respect, the biosynthesis of 2 differs from that of vitamin K2 The possible biochemical significance of 2 , which we can also think of as deoxyubiquinone, in the mitochondrial respiratory chain remains to be investigated. It would obviously be of great interest if this new compound is found to be present in mitochondria. Ubiquinone and tocopherol are present, but tocopherylquinonc is not. If the new vitamin compound were found in mitochondria, it would clearly support those who would ascribe to vitamin some specific function in respiratory-enzyme systems. This possibility has existed ever since the... 

Other quinones are phylloquinone (vitamin K,), menaquinone (vitamin K2), ubiquinone, and plastoquinone. The latter two have partly unsaturated chains. Ubiquinone and phylloquinone contain a varying number of isoprene units of the type -CH2-CH=C(CH3)-CH2 (Figure 11.8), but in phylloquinone only the first unit is unsaturated. The others are saturated -CH2-CH2-CH(CH3)-CH2 units, with a much higher flexibility than the partly unsaturated ones. The vitamin K quinones promote coagulation of the blood. 

The best-known representative, isolated from pig and beef heart muscle, contains a Cso side chain and has therefore been designated ubiquinone(50) and coenzyme Qio. A lower isoprenolog, isolated from yeast and with a Cso side chain, is called ubiquinone(30). Further compounds isolated from microbial sources contain Cst, C40, and C4S side chains, respectively. The identity of the side chains of the ubiquinones with those of the vitamin K2 compounds is remarkable. 

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