Phytylation step

Liljenberg (1977a) has reviewed the phytylation step in chlorophyll biosynthesis and has presented evidence for the presence of phytyl pyrophosphate and acyl esters of phytol in irradiated barley seedlings (Liljenberg, 1977b). 

Animals caimot synthesize the naphthoquinone ring of vitamin K, but necessary quantities are obtained by ingestion and from manufacture by intestinal flora. In plants and bacteria, the desired naphthoquinone ring is synthesized from 2-oxoglutaric acid (12) and shikimic acid (13) (71,72). Chorismic acid (14) reacts with a putative succinic semialdehyde TPP anion to form o-succinyl benzoic acid (73,74). In a second step, ortho-succmY benzoic acid is converted to the key intermediate, l,4-dihydroxy-2-naphthoic acid. Prenylation with phytyl pyrophosphate is followed by decarboxylation and methylation to complete the biosynthesis (75). 

Figure 16.10 Biosynthesis of phylloquinone (vitamin K-j) from 1,4-dihydroxynaphthoic acid. The key step that joins the 20-carbon phytyl side chain to the aromatic ring is a Friedel-Crafts-like electrophilic substitution reaction.

In the past, no snitable analytical methodologies were capable of investigating these multiple reactions and even today, the complete extraction and analysis of all the componnds is still a difficult task. The methods for extraction must be optimized for each sample according to the solubility of either phytylated (chlorophylls and pheophytins) or dephytylated (chlorophyllides and pheophorbides) derivatives, often requiring several repeated steps and the use of a single or a mixture of organic solvents. 

H3PW12O40 and H4SiWi204o are also active for the condensation of isophytol and l-acetoxy-4-hydroxy-2-methylnaphthalene, which is a key step in the synthesis of vitamin K (2-methyl-3-phytyl-1,4-naphthoquinone) [Eq. (43)] heteropolyacids are approximately 50 times more active than ZnCl2 (362). 

Vitamin K cycle—metabolic interconversions of vitamin K associated with the synthesis of vitamin K-dependent clotting factors. Vitamin K1 or K2 is activated by reduction to the hydroquinone form (KH2). Stepwise oxidation to vitamin K epoxide (KO) is coupled to prothrombin carboxylation by the enzyme carboxylase. The reactivation of vitamin K epoxide is the warfarin-sensitive step (warfarin). The R on the vitamin K molecule represents a 20-carbon phytyl side chain in vitamin Ki and a 30- to 65-carbon polyprenyl side chain in vitamin K2. 

The earliest steps (MVA to GGPP) for polyisoprenoid biosynthesis are identical for all plants and animals (12,13). They involve the well-known diterpene pathway, MVA — MVAP — MVAPP — IPP + DMAPP — GPP — FPP — GGPP. The enzymes catalyzing these steps have been studied extensively, especially from animals (liver) and yeast, and to a more limited extent from higher plants. In some cases the enzymes have been purified to homogeneity most have been only partially purified. In both plants and animals a major branch at FPP leads to the production of squalene and the steroids. In plants, three major branches occur at GGPP, of which one leads to the carotenoids via phyto-ene, a second to the phytyl group of chlorophyll, and a third to the GAs. 

Fig. 1 Schematic representation of the spatial arrangement of the chromophores involved in the first steps of photosynthetic charge-separation in rhodopseudomonas viridis. Orientation of phytyl side-chains is indicated by wavy lines, furthermore the position of an additional bacteriochlorophyll unit is sketched.

Returning to the photosynthetic system it now seems plausible that the explanation for the short charge-separation times in the primary steps must be found in the nature of the medium between the redox-sites involved. In this connection it is interesting to note that saturated hydrocarbon chains (i.e. phytyl sidechains) extend from the special pair and from the menaquinone towards the intermediate bacteriopheophytin (see Fig.l). At this moment it is not clear, however, whether in rhodopseudomonas viridis any of these phytyl sidechains plays the role of a molecular wire (see also Kuhn, 1986) that we attribute to the hydrocarbon bridges in l(n). For rhodopseudomonas sphaeroides a fivefold decrease in the rate of the reverse electron transfer from the quinone (ubiquinone) to the bacteriopheophytin was recently reported to result upon removal of the isoprenoid sidechain from the quinone (Gunner et al., 1986). 

A synthesis of (S)-cx-tocotrienol, in which the phytyl group of tocopherol is replaced by a famesyl side chain, (six steps, 19% ee = 98%) is based on the enzymatic desymmetrisation of the achiral 2,2-di(hydroxymethyl)chroman 16 <02TL7971>. 

A new, efficient synthesis of ubiquinone (249) has been described.115 In the key step, 6-bromo-2,3-dimethoxy-5-methylhydroquinone diacetate (257) is treated with l,l-dimethyl-7r-allyl-, 7r-geranyl-, 7r-solanesyl-, ir-decaprenyl-, or 7r-phytyl-nickel bromide (258)—(262) in HMPA at 60 °C, to afford a 70% yield of 2,3-dimethoxy-5-methyl-6-prenylhydroquinone diacetate (263). Ubiquinones-1, -2, -9, and -10 (250)—(253) and 6, 10, 14 -hexahydroubiquinone-4 (254) have been prepared by this method. The preparation of tritium-labelled 5-demethoxy-ubiquinone-9 (255) has been described.116... 

An easy synthesis of prenyl naphthoquinones, e.g. menaquinone-2 (205 n = 2), was achieved by coupling the appropriate prenyl halide with an organo-copper derivative of the electrochemically derived quinone bisacetal (216). Menaquinone-2 and phylloquinone (204) were also obtained in good yields by reaction of 2-methyl-1,4-naphthoquinone (205 n =0) with geranyl and phytyl halides in the presence of metal dust. A one-step method for the preparation of vitamin K analogues uses cyclodextrin inclusion catalysts.Thus reaction of the diol (217) with allyl bromide in the presence of oxygen and/3-cyclodextrin at pH 9 afforded the menaquinone analogue (218). 

FIGURE 54-6 The vitamin K cycle y-glutamyl carboxy lotion of vitamin K-dependentpr( eins. The enzyme -glutamyl carboxylase couples the oxidation of the reduced hydroquinone form (KH2) of vitamin Kj or K2, to -carboxylation of Glu residues on vitamin K-dependent proteins, generating the epoxide of vitamin K (KO) and 7-carboxyglutamate (Gla) residues in vitamin K-dependent precursor proteins in the endoplasmic reticulum. A 2,3-epoxide reductase regenerates vitamin KH2 and is the warfarin-sensitive step. The R on tiie vitamin K molecule represents a 20-carbon phytyl side chain in vitamin and a 5- to 65-carbon prenyl side chain in vitamin K2. 

Vitamin K. Vitamin K can be obtained in 60-65% yield in one step by reaction of 2-methyl-1,4-naphthoquinone with phytyl chloride in THF in the presence of zinc dust. Other metals are less satisfactory. ... 

The final step in the biosynthetic pathway to chlorophylls is the esterification of the chlorophyllides with phytyl diphosphate or geranylgeranyl diphosphate (followed by reduction of the three extra double bonds) via the enzyme chlorophyll synthetase. Once again, when zinc or cadmium replaces magnesium, esterification is unaffected. However, when nickel or copper are used, esterification is hindered. Presumably the labile coordinating power of the group Ila and Ilb metals, as opposed to the more inert coordination of transition metals, is involved in the function of the two enzymes, oxidative cyclase and chlorophyll synthetase. 

The common intermediate of haem and chlorophyll pigments biosynthesis, protoporphyrin IX, is transformed into chlorophyUde by a sequence of several reaction steps. Chlorophyll a arises from chlorophyHde in a reaction with phytyl diphosphate that is produced by the reduction of geranylgeranyl diphosphate. Oxidation of the C-7 methyl group in chlorophyll a to a formyl group yields chlorophyll b. 

Transcripts that encode all of the enzymes involved in the biosynthesis of vitamin E are elucidated in Table 18.2. The identified enzymes used to reconstruct the pathway of vitamin E bios5mthesis are presented in Fig. 18.3. The vitamin E biosynthetic pathway in D. tertiolecta is similar to that of the plant AraUdopsis thaliana, and the cyanobacterium Synecho-cystis sp. D. tertiolecta utilizes the metabolism of the aromatic amino acid tyrosine for the s5mthesis of the polar head group, whereas the unsaturated tail is derived from phytyl-pyrophosphate (PPP), which is a metabolite of terpenoid backbone biosynthesis (DellaPenna and Pogson, 2006). The committed step in the synthesis of the head group is catalyzed by the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27), which converts... 

The only known function of PhQ in cyanobacteria and plants is to function as an electron transfer cofactor in PS I. In spite of its importance in cyanobacteria, the biosynthetic route of PhQ was not previously elucidated. Many prokaryotes contain the metabolic pathway for the biosynthesis of menaquinone (MQ), a PhQ-Hke molecule (Figure 119.1). In certain bacteria, MQ is used during fumarate reduction in anaerobic respiration. - In green sulfur bacteria and in heliobacteria, MQ may function as a loosely bound secondary electron acceptor in the photosynthetic reaction center. The genes encoding enzymes involved in the conversion of chorismate to MQ were cloned in a variety of organisms. MQ differs from PhQ only in the tail portion of the molecule an unsaturated C-40 side chain is present, rather than a mostly saturated C-20 phytyl side chain. Therefore, the synthesis of the naphthalene rings in PhQ and MQ involves similar steps in both pathways. 

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