The synthesis of all N-linked glycoproteins begins with the synthesis of a branched oligosaccharide attached to dolichol pyrophosphate (Figure 1) on the cytosolic side of the endoplasmic reticulum membrane, which is then translocated to the lumen of the endoplasmic reticulum, where it under goes further glycosylation, before the oligosaccharide chain is transferred by an oligosaccharyltransferase onto an asparagine residue of the acceptor apoglycoprotein as it enters the endoplasmic reticulum during synthesis on membrane-bound polyribosomes. This is thus a cotranslational modification. In many of the N-linked glycoproteins there is a consensus sequence of Asn-X-Ser/Thr (where X = any amino acid other than proline) that determines the site of glycosylation; in others there is no clear consensus sequence for glycosylation.

Fig1. The structure of dolichol.The group within the brackets is an isoprene unit (n = 17-20 isoprenoid units).

As shown in Figure 2, the first step is a reaction between UDP-N-acetylglucosamine and dolichol phosphate, forming N-acetylglucosamine dolichol pyrophosphate. A second N-acetylglucosamine is added from UDP-N-acetylglucosamine, followed by the addition of five molecules of mannose from GDP-mannose. The dolichol pyrophosphate oligosaccharide is then translocated into the lumen of the endoplasmic reticulum, and further mannose and glucose molecules are added, to form the final dolichol pyrophosphate oligo saccharide, using dolichol phosphate mannose and dolichol phosphate glucose as the donors. The dolichol pyrophosphate oligosaccharide is then transferred onto the acceptor asparagine residue of the nascent protein chain.

Fig2. Pathway of biosynthesis of dolichol pyrophosphate oligosaccharide. Note that the first five internal mannose residues are donated by GDP-mannose, whereas the more external mannose residues and the glucose residues are donated by dolichol-P-mannose and dolichol-P-glucose. (Dol, dolichol; GDP, guanosine diphosphate; P, phosphate; UDP, uridine diphosphate; UMP, uridine monophosphate.)

To form high-mannose chains, the glucose and some of the peripheral mannose residues are removed by glycosidases. To form an oligosaccharide chain of the complex type, the glucose residues and four of the mannose residues are removed by glycosidases in the endoplasmic reticulum and Golgi, then N-acetylglucosamine, galactose, and N-acetylneuraminic acid are added in reactions catalyzed by glycosyltransferases in the Golgi apparatus. Hybrid chains are formed by partial processing, forming complex chains on one arm and mannose units on the other arm.

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خبراء يكشفون تأثير الاستحمام في الظلام على جودة النوم !

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مواضيع ذات صلة

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There are Three major classes of Glycoproteins

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Biochemical Markers of Bone Remodeling in Different Clinical Conditions Affecting Bone Tissue Metabolism

Free Radicals & Antioxidant Nutrients

Vitamin B12 is Found only in Foods of Animal Origin

Vitamin B6 is important in Amino Acid & Glycogen Metabolism & in Steroid Hormone Action

Niacin is not Strictly A Vitamin

Bone Tissue Biochemistry

Vitamin K is required for synthesis of blood-clotting proteins

Vitamin E does not have a precisely defined metabolic function

Vitamin D is really a hormone