Biochemistry: The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Biosynthesis: How New Molecules Are Formed
Polysaccharide Synthesis
Highly Specific Transferases

As discussed earlier, we examined the synthesis of one of the Homopolysaccharides, Glycogen (Ch. 11, Section E,3). In animals, glycogen is synthesized from UDP-glucose, whereas in Bacteria it is formed from ADP-glucose. The latter compound also serves as a donor of glucosyl units in starch synthesis (Fig. 12-1) [10a]. Branched molecules of glycogen and amylopectin grow from the non-reducing ends of the chain. The combination of growth and degradation at the same ends of the molecule ensures the rapid accumulation or utilization of glucosyl units. A similar mechanism of glucose residue transfer from UDP derivatives to the non-reducing ends of the carbohydrate chain is also characteristic of the synthesis of many oligosaccharide groups linked to Proteins and Lipids.

The synthesis of complex Polysaccharides via genetically determined reaction sequences has already been briefly discussed (Ch. 11, Section E,3). Here we examine The formation of such polysaccharides as hyaluronic acid and chondroitin sulfate, along with their distinct terminal structural units (Ch. 2, Sections B,3 and B,4). The synthesis of these compounds requires the sequential action of a large set of specific transferases. The first transferase transfers a xylose residue from UDP-xylose to the OH group of a Serine residue in the protein. Next, a specific enzyme transfers galactose from UDP-galactose to xylose, linking the sugar residues via a 1,4-bond. A third enzyme transfers the next galactose residue to the first, forming a 1,3-bond. Subsequently, a specialized glucuronic acid transferase, distinct in Specificity from The enzyme catalyzing the Synthesis of the main chain, completes the Formation of the serine-linked terminal structural unit. Then, the subsequent transfer reactions proceed through the sequential action of two Enzymes. In the case of hyaluronic acid synthesis, one enzyme, specific for UDP-GlcNAc, catalyzes The transfer of this carbohydrate residue exclusively to the end of the glucuronic acid chain. The second enzyme, characterized by specificity for UDP-glucuronic acid, attaches a glucuronic acid residue solely to the terminus of the N-acetylglucosamine unit. The formation of chondroitin sulfates proceeds via another pair of enzymes with different specificities (see Structure in Fig. 2-16). The attachment of sulfate groups to the corresponding sites requires additional specific transferases.

The addition of a carbohydrate unit to Cell Membrane Proteins or to proteins secreted by The Cell is mediated by specialized transferases. As an example, let us consider the synthesis of Blood Group Antigens. The Role of specific Glycosyltransferases in determining blood group specificity has already been discussed in Ch. 5, Section B,1.