Polyprenols pyrophosphate

Dolichol is related to vitamin A (10.66a), the phosphate ester of which may also be involved in glycosyl transfer reactions in the body (Chapter 11). Polyprenol pyrophosphates are involved in the biosynthesis of rubber, gutta-percha and other terpenes (Chapter 11.5). 

The mechanism for the polymerization of the teichoic acids has not been definitively established, but it is most probably very similar to the biosyntheses of the other lipid-coenzyme-dependent polysaccharides, the peptidomurein and Salmonella 0-antigen polysaccharide, in which the monomer unit or repeating unit attached to the lipid polyprenol pyrophosphate carrier is inserted between the growing chain and the lipid coenzyme carrier. See Fig. 10.12B for the proposed mechanism for teichoic acid biosynthesis. 

The complete biosynthesis of xanthan, a water-soluble bacterial polysaccharide with a cellulose backbone (see Chapter 6, Fig. 6.18 for the structure), has been worked out by Dankert et al. [111-114]. The pentasaccharide repeating unit is attached to a polyprenol pyrophosphate lipid carrier [111], and the polymerization takes place by the addition of the repeating pentasaccharide from the polyprenol pyrophosphate pentasaccharide to the reducing end of the growing xanthan chain [114]. The mechanism of xanthan chain elongation is an insertion mechanism similar to those of murein. Salmonella 0-antigen, the dextrans, mutan, and alteman. 

The Css polyprenol (154) obtained from leaves of Magnolia campbelUi has been shown to be a mixture of cis- and /ran -isomers. The preparation of dolichyl phosphate (155) by a pea cell-free extract has been described. Evidence has been obtained that a lipid, containing 7V-acetylglucosamine, which was obtained from Phaseolus vulgaris hypocotyls, consists of a mixture of the dolichol (156) derivatives dolichyl pyrophosphate N-acetylglucosamine and dolichyl pyrophosphate di-N-acetylchitobiose. ... 

Polyterpenoids.—The presence of dolichols (202) with up to 23 isoprene units, in various sources, has been reported.In addition to these dolichols, which have their terminal isoprene unit saturated, fully unsaturated polyprenols have been found. Bovine pituitary contains a mixture of cis-trans-isomers of decaprenol (203), a Cioo prenol from bovine thyroid has been shown by n.m.r. to have eighteen cis- and two frans-isoprene residues, and 2,3-dehydrodoli-chyl pyrophosphate (204) has been identified as a product of a chick enzyme system and isopentenyl pyrophosphate.The structure of ulmoprenol from Eucommia ulmoides has been elucidated (207). ... 

The )8-(1 2)- and a-(1 5)-linked arabinose residues are incorporated into the polymer from the activated polyprenyl sugar phosphate 10, which is in turn synthesized from glucose via 5-phosphoribose pyrophosphate (pRpp) [46-48]. Elongation of the polymer chain is believed to involve a family of arabinosyltransferases (AraT s) that recognize both 10 and arabinofuranoside-based acceptors of differing structures (Fig. 5) [18,19,49,50]. In AG biosynthesis, the entire polysaccharide appears to be assembled as a polyprenol diphosphate intermediate, which is transferred to peptidoglycan prior to the addition of the mycolate esters [18]. In LAM biogenesis, the arabinan portion is believed to be synthesized as a polyprenol phosphate that is transferred to lipomannan [51]. 

The chemical structure of naturally occurring ais polyisoprenes was determined by 13C NMR spectroscopy using acyclic terpenes and polyprenols as model compounds. The arrangement of the isoprene units along the polymer chain was estimated to be in the order dimethylallyl terminal unit, three trans units, a long block of ais units, and ais isoprenyl terminal unit. This result demonstrates that the biosynthesis of cis-polyisoprenes in higher plants starts from trans,trans,trarcs-geranylgeranyl pyrophosphate. ... 

This alignment of the trans and cis units clearly indicates that these polyprenols are synthesized in vivo by the cis addition of isopentenyl pyrophosphate to trans,trans,trems-geranylgeranyl pyrophosphate (10). 

The polyprenols composed of trans and cis isoprene units isolated so far have been classified into two types the ficaprenoltype and the betulaprenol-type, containing three and two internal trans units, respectively (12). The findings described above suggest that trans,trans,tra s-geranylgeranyl pyrophosphate or trans,trans-farnesyl pyrophosphate acts as an initiator of the biosynthesis of polyprenols. 

Dolichol phosphate, which is a crucial intermediate, has been shown to be synthesised in a variety of tissues and subcellular fractions, of which mitochondrial outer membranes are especially active. These are also a major store of dolichol. The synthesis can start from isopentenyl pyrophosphate or its precursor, mevalonic acid (see the reviews of Beytia and Porter, 1976 Daleo and Pont-Lezica, 1977 Daleo etaiy 1977). In one case the product was the a-unsaturated polyprenol phosphate (dehydrodolichol phosphate), which suggests that a-saturation may occur after phosphorylation, at least in tissues such as hen oviduct (Grange and Adair, 1977 Adair and Keller, 1982). 

The biosynthesis of the mannan inner core involves dolichol pyrophosphate derivatives containing JV-acetyl glucosamine and several mannose residues [38]. The participation of the polyprenol (dolichol) in the biosynthesis of the mannan inner core in yeast is analagous to its role in animal tissues as a mechanism for the glycosylation of proteins. 

Another compound of interest is dolichol which was first isolated from liver and is now known to be present in many other animal tissues. It is a long chain molecule (n=17-21), its first isoprene residue is saturated and it has 2 trans double bonds. It is found in liver part as the free alcohol and another part esteri-fied with fatty acids. We now know that a small amount is present as the phosphate or pyrophosphate and may have various sugars joined to it. These dolichol derivatives are involved in the glycosylation of proteins. An excellent review on polyprenols has been written by Hemming (1974). 

All ra 5-polyprenols are believed to be formed from GFPP by the chain extension process already discussed (Sect. 8.1.1.2), followed by hydrolysis by appropriate phosphatases. There is evidence to show that synthesis of all- raAi -poly-prenol pyrophosphates occurs in mitochondrial membranes and chloroplasts. Biosynthetic studies have shown that c/5, ra 5-polyprenols are synthesized from FPP or GGPP by cw-prenylation by IIP (189, 369, 392). 

Synthesis of the lipid moiety dolichol occurs in the cytoplasm and endoplasmic reticulum, beginning with steps identical to those of cholesterol biosynthesis, up to and including the formation of farnesyl pyrophosphate [7]. At this point, the synthesis pathways of cholesterol and dolichol branch, with dolichol synthesis proceeding with the addition of isoprenyl units to farnesyl pyrophosphate by cis-prenyltransferase, yielding polyprenylpyrophosphate as the product. An important step in the synthesis of dolichol is the reduction of polyprenol, with a double bond in every isoprene unit, to dolichol, in which the a isoprene, the one nearest the hydroxyl unit, is saturated (Figure 1 and [7]). 

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