The Biosynthesis of Glycoproteins

Enzymic transfer of D-xylose from uridine 5 -(D-xylopyranosyI-HC pyrophosphate) to L-serine residues of endogenous protein acceptors from (a) a cell tumor of the mouse188 and (b) chick-embryo cartilage189 occurs in cell-free extracts of both of these tissues, in the absence of biosynthesis of protein. The enzyme preparations employed were from the supernatant liquor, although activity was also present in the insoluble fractions. In these two types of tissue, the acceptors are heparin and chondroitin sulfate, respectively, but the presence of other D-xylose-containing glycoproteins in ascites fluid from 

A large number of glycosyl ester nucleotide transferases are known to exist these include those involving cytidylic acid-sialic acid336,337 

The incorporation of sulfate into the carbohydrate moieties of glycoproteins occurs after incorporation of the sugar moieties, and thus, here again, is a post-ribosomal event. The process is, therefore, not directly under control of the genome. 

Sulfation of the sugar moieties of chondroitins occurs by a sequence of steps, the first of which involves formation of 3 -0-phosphono-5 -adenylyl hydrogen sulfate, the sulfate donor.346,347 This enzyme is present in a number of the tissues in which these glycoproteins 

As already mentioned (see p. 470), it is probable that sulfation of the carbohydrate chains occurs, to a considerable extent at least (if not wholly), after the polymerization has occurred. This probability was suggested by Meyer and coworkers,351352 because of their finding of chondroitin in ox cornea that was free from, or very low ( 2%) in, sulfate this substance was later shown to be enzymically sulfated by extracts of the isthmus of hen oviduct at a higher rate than all other substances assayed.353 

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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). 

Table 47-15. Some diseases due to or involving abnormalities in the biosynthesis of glycoproteins.

Mucins are a class of O-linked glycoproteins that are distributed on the surfaces of epithelial cells of the respiratory, gastrointestinal, and reproductive tracts. The Golgi apparatus plays a major role in glycosyla-tion reactions involved in the biosynthesis of glycoproteins. 

Besides cell-wall polysaccharides, plants contain glycoproteins, as do animal cells, and it is in the biosynthesis of glycoprotein that evidence for involvement of lipid-linked sugars has accumulated. Most of the data have been obtained for animal cells, and the subject is well covered in several reviews.1113178 Since 1964, when glycoproteins were first detected in plants,179 their wide distribution has become evident, and reviews are available.15,16,180 We shall describe aspects of this subject not as yet covered. 

Nojirimycin (5-amino-5-deoxy-D-glucose) is an antibiotic used in studies of the biosynthesis of glycoproteins. Write its open-chain and pyranose ring structures. 

Fig. 16. Schematic presentation of the present hypotheses on the biosynthesis of glycoprotein of halobacteria (for details see the text). From ref. [117].

The reaction sequences by which glycoproteins of yeasts and fungi are synthesized are not completely understood. A portion of the work on the biosynthesis of glycoproteins in yeast conducted in Ballou s laboratory is discussed elsewhere in this volume (J.) and therefore will not be considered here. 

D. and their esters are present in practically all membranes of eukaryotic cells (except those of mitochondria and plastids) and function in the biosynthesis of glycoproteins and glycolipids as carriers of and transport molecules for oligosaccharides. D. are also com-... 

The role of undecaprenyl phosphate (C55, allylic) as a carrier of glycosyl units in the biosynthesis of bacterial cells walls is well established. Dolichyl phosphate plays a similar role in the synthesis of glycoproteins in animal systems. Evidence that prenyl lipids serve as glycosyl carriers in the biosynthesis of glycoproteins in plants is accumulating rapidly (Pont Lezica et al., 1976 Delmer al., 1978 Erickson et al., 1978). Several authors have recently reviewed the literature on the role of polyprenols as glycosyl carriers in plants (Hemming, 1978 Pont Lezica, 1979 Elbein, 1979). 

The biosynthesis of glycoproteins in the retina of chicken embryos involves the partition of o-mannolipids. ... 

Derivatives of cholesterol which inhibit the biosynthesis of cholesterol in aortic smooth muscle, presumably by suppressing the activity of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, also effect a corresponding decrease in the levels of glycosylated lipid intermediates with an apparent inhibition of the biosynthesis of glycoproteins. ... 

Compound (602b) has been suggested as a carrier molecule in the biosynthesis of glycoproteins, and it has been possible to synthesize it by an in vitro enzymatic reaction (De Luca et aL, 1979 Rask and Peterson, 1980). 

The biosynthesis of glycoproteins is reviewed twice once in connection with glycosaminoglycans and again in a separate section dealing with the assembly and attachment of carbohydrates to proteins to give macromolecules that are not glycosaminoglycans. 

Lipid intermediates are formed during the biosynthesis of glycoproteins in microsomes. Column chromatography was used to separate dolichyl D-[ C]mannosyI phosphate from a D-[ C]manno-oligosaccharide which was also bound to lipid after removal of the lipid, the oligosaccharide fraction appeared to be heterogeneous in its reaction with concanavalin A. 

The assembly of the macroinolecuJar proteoglycans from small precursor molecules presents a number of problems which arc also encountered in other fields, especially the biosynthesis of glycoproteins. Apart from the special features in the biosynthetic pathways, which arise from the presence of two major, covalently linked components, the synthesis of... 

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