Dolichyl phosphates

Long-chain polyisoprenoid. molecules with a terminal alcohol moiety are called, polyprenols. The dolichols, one class of polyprenols (Figure 8.18), consist of 16 to 22 isoprene units and, in the form of dolichyl phosphates, function to carry carbohydrate units in the biosynthesis of glycoproteins in animals. Polyprenyl groups serve to anchor certain proteins to biological membranes (discussed in Chapter 9). 

This enzyme [EC 2.4.1.83] which catalyzes the following reaction GDP-mannose + dolichyl phosphate to yield GDP -h dolichyl D-mannosyl phosphate. 

PROTON INVENTORY TECHNIQUE Dolichyl-phosphate mannosyltransferase,... 

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. ... 

Pont Lezica355 speculated that the role of dolichyl phosphates, a-satu-rated polyisoprenyl phosphates of chain length between 80 and 105 carbon atoms, in glycosyl transfer during biosynthetic mechanisms is a general feature of eukaryotic cells, whereas, in prokaryotic cells, the lipids fulfilling this function are a-saturated polyisoprenyl phosphates of shorter chain-length, such as undecaprenyl phosphate (which contains 55 carbon atoms). 

Further work in plant systems confirmed, by different methods (biosynthesis from mevalonate,27 28 mass spectrometry,33 and the techniques already mentioned30), that the polyprenyl phosphate involved in glycosyl-transfer reactions is dolichyl phosphate. Table II shows different sources from which dolichyl phosphate has been identified in plants. 

SCHEME 1.—The Biosynthesis and Metabolism of Dolichyl Phosphate and Other Plant Isoprenoids. 

Grange and Adair73 isolated 2,3-dehydrodolichyl phosphate from in vitro studies on hen oviduct. It may be derived from 2,3-dehydrodolichyl diphosphate, a likely intermediate in the biosynthesis of dolichyl phosphate. Many questions still remain unanswered, such as is the substrate for the a-isoprene reductase, the diphosphate or the monophosphate of 2,3-dehy-drodolichol Are the unsaturated polyprenols a reserve pool for the synthesis of dolichol in plants What is the function of unsaturated, plant polyprenols How is the synthesis of saturated and unsaturated polyprenols regulated ... 

Dolichyl phosphate phosphatase has been described in animal tissues,74-76 and it is possibly responsible for the free dolichol found in tissues. This free dolichol can be rephosphorylated by a dolichol kinase using cytidine triphosphate (CTP) as phosphoric donor,77-78 or acylated by a dolichol acyltransferase79 (see Scheme 1). 

The concentration of dolichyl phosphate in eukaryotic tissues is very low and is probably rate-limiting for the glycosylation processes. Variation of the concentration in the endoplasmic-reticulum membranes is a possible way of controlling the rate of glycosylation. It is important to point out that the early steps in the dolichol biosynthesis are common to such other prenyl derivatives in plants as steroids, essential oils, hormones, phytol, and carotenes (see Scheme 1), and parameters affecting those reactions that may control the dolichol to dolichyl phosphate step could be another mechanism for regulation of the level of dolichyl phosphate. 

In those cases in which the initiation of polysaccharide chains is mediated by lipid-linked saccharides, it becomes clear that the level of dolichyl phosphate must be important for regulation. Because no experimental evidence is available at present, further work will be necessary in order to elucidate the regulation mechanisms. 

Figure 6.4 Two possible pathways for dolichyl diphosphate dephosphorylation in yeast cells Dol-PP, dolichyl diphosphate Dol-P, dolichyl phosphate.

Figure 6.5 The tentative coupling of PolyP and mannan biosynthesis in yeast Dol-PP, dolichyl diphosphate Dol-P, dolichyl phosphate GDPMan, GDPmannose Dol-PP-Man, dolichyl diphosphate mannose (Man) , mannan, where n is the number of mannose residues.

The putative pathway of coordination of mannan and PolyP biosynthesis by cell-wall formation has been proposed (Kulaev, 1994), which explains the presence of PolyP outside of the cytoplasmic membrane (Figure 7.4). Dolichyl-phosphates (Dol-Ps) act as transmembrane carriers of carbohydrate residues in glycoprotein biosynthesis. GDP-mannose at the... 

Yasugi, E., Yokoyama, Y., Seyama, Y., Kano, K., Hayashi, Y., and Oshima, M., 1995, Dolichyl phosphate, a potent inducer of apoptosis in rat glioma C6 cells. Biochem. 

Longer chain isoprenoids are synthesized via two other isoprenyl diphosphate enzyme systems in mammals [21]. Long E-isoprenyl diphosphate synthase (IDS) produces the side chains of ubiquinone. The length of the side chain varies amongst species, and in humans a C50 synthase has been identified [22]. Dehydrodolichyl diphosphate synthase, the only Z-IDS found in mammals, is responsible for the synthesis of the sugar carriers dohchol and dolichyl phosphate [23]. Plants have additional Z-IDS which can catalyze the production of very long isoprene species, such as natural... 

Ion conduction is increased when membrane fluidity is increased and molecular packing is decreased. The insertion of polar groups into the hydrocarbon core can increase the fluidity of a membrane by preventing close packing of acyl chains [53]. In contrast, low concentrations of lipophilic molecules such as dolichyl phosphate are oriented in a membrane with their... 

The biosynthesis of the N-linked oligosaccharide chain is initiated by the assembly of the high mannose type of oligosaccharide on the ER membrane (Figure 2). This assembly process involves the participation of a carrier molecule called dolichyl-phosphate (Dol-P), which is a component of the ER membrane, and is a lipid structure... 

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