Glycosyl Group Transferases

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Glycosyl group transfer underlies the biosynthesis and breakdown of all nucleotides, polysaccharides, glycoproteins, glycolipids, and glycosylated nucleic acids, as well as certain DNA repair processes. Glycosyl transfer consists of the transfer of the anomeric carbon of a sugar derivative from one acceptor to another, as in, which describes the transfer of a generic pyranosyl ring between nucleophilic atoms :X and :Y of acceptor molecules. The stereochemistry at the anomeric carbon is not specified in eq. 12-1, but the leaving group occupies the axial position in an α-anomer or the equatorial position in a β-anomer. The overall transfer can proceed with either retention or inversion of configuration. In biochemistry, the acceptor atoms can be oxygen, nitrogen, sulfur, or in the biosynthesis of C-nucleosides even carbon. The great majority of biological glycosyl transfer reactions involve transfer between oxygen atoms of different acceptor molecules. Enzymes catalyzing glycosyl transfer are broadly grouped according to whether the acceptor :Y–R2 in is water or another molecule. In the actions of glycosidases, the acceptor is water, and glycosyl transfer results in hydrolysis of a glycoside, a practically irreversible process in dilute aqueous solutions. In the action of glycosyltransferases, the acceptors are molecules with hydroxyl, amide, amine, sulfhydryl, or phosphate groups. The simplest nonenzymatic glycosyl transfer reaction is the hydrolysis of a glycoside, and early studies revealed the fundamental fact that glycosides are much less reactive toward hydrolysis in basic solutions than in acidic solutions. This fact underlies much that is known about the mechanism of glycosyl transfer; that is, the anomeric carbon of a glycoside is remarkably unreactive toward direct nucleophilic attack, but it becomes reactive when one of the oxygens is protonated by an acid, as illustrated in fig. 12-1 for the acid-catalyzed hydrolysis of a generic glycoside. The reaction by both mechanisms in fig. 12-1 proceeds by pre-equilibrium protonation of the glycoside to form oxonium ion intermediates, which are subject to hydrolysis by water. The two mechanisms in fig. 12-1 are of interest. The mechanism proceeding through exocyclic cleavage of the glycoside has historically been regarded as the more likely, and for this reason, the route through endocyclic cleavage has received little consideration.