Harpers

516 / CHAPTER 47Table 47–4. The principal sugars found in human glycoproteins. Their structures are illustrated inChapter 13.NucleotideSugar Type Abbreviation Sugar CommentsGalactose Hexose Gal UDP-Gal Often found subterminal to NeuAc in N-linked glycoproteins.Also found in core trisaccharide of proteoglycans.Glucose Hexose Glc UDP-Glc Present during the biosynthesis of N-linked glycoproteinsbut not usually present in mature glycoproteins.Present in some clotting factors.Mannose Hexose Man GDP-Man Common sugar in N-linked glycoproteins.N-Acetylneur- Sialic acid (nine NeuAc CMP-NeuAc Often the terminal sugar in both N- and O-linkedaminic acid C atoms) glycoproteins. Other types of sialic acid are alsofound, but NeuAc is the major species found in humans.Acetyl groups may also occur as O-acetylspecies as well as N-acetyl.Fucose Deoxyhexose Fuc GDP-Fuc May be external in both N- and O-linked glycoproteinsor internal, linked to the GlcNAc residue attachedto Asn in N-linked species. Can also occurinternally attached to the OH of Ser (eg, in t-PA andcertain clotting factors).N-Acetylgalactosamine Aminohexose GalNAc UDP-GalNAc Present in both N- and O-linked glycoproteins.N-Acetylglucosamine Aminohexose GlcNAc UDP-GlcNAc The sugar attached to the polypeptide chain viaAsn in N-linked glycoproteins; also found at othersites in the oligosaccharides of these proteins.Many nuclear proteins have GlcNAc attached to theOH of Ser or Thr as a single sugar.Xylose Pentose Xyl UDP-Xyl Xyl is attached to the OH of Ser in many proteoglycans.Xyl in turn is attached to two Gal residues,forming a link trisaccharide. Xyl is also found in t-PAand certain clotting factors.NUCLEOTIDE SUGARS ACTAS SUGAR DONORS IN MANYBIOSYNTHETIC REACTIONSThe first nucleotide sugar to be reported was uridinediphosphate glucose (UDP-Glc); its structure is shownin Figure 18–2. The common nucleotide sugars involvedin the biosynthesis of glycoproteins are listed inTable 47–4; the reasons some contain UDP and othersguanosine diphosphate (GDP) or cytidine monophosphate(CMP) are obscure. Many of the glycosylation reactionsinvolved in the biosynthesis of glycoproteinsutilize these compounds (see below). The anhydro natureof the linkage between the phosphate group andthe sugars is of the high-energy, high-group-transferpotentialtype (Chapter 10). The sugars of these compoundsare thus “activated” and can be transferred tosuitable acceptors provided appropriate transferases areavailable.Most nucleotide sugars are formed in the cytosol,generally from reactions involving the correspondingnucleoside triphosphate. CMP-sialic acids are formedin the nucleus. Formation of uridine diphosphate galactose(UDP-Gal) requires the following two reactions inmammalian tissues:UTP + Glucose 1-phosphateUDP-GlcUDP-GlcPYROPHOS-PHORYLASEUDP-GlcEPIMERASEUDP-Glc + PyrophosphateUDP-Gal