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The Essentials of Nucleotide Sugars !
!Lance Wells
X 11
Sugar Activated form Glc
] UDP-sugar
Gal GlcNAc GalNAc GlcA Xyl Man ] GDP-sugar Fuc Sia ] CMP-Sia !
Sugar Nucleotides (high energy donors) in Mammals
What mammalian sugars are missing? IdoA (epimerized in glycan chains, not added)
Ribitol (CDP-ribitol, new sugar nucleotide/O-Man structures)
Glucose is only Sugar Needed for Synthesis of All Sugar Nucleotides
Note: No salvage Pathway for GlcA!
Key Control Points: Early step enzymes that are inhibited by end-‐product Sugar nucleo<de
Salvage PathwaysExample: Glc à Glc-6-P à Glc-1-P à UDP-Glc
Example: Fuc à Fuc-1-P à UDP-Fuc
Example: Neu5Ac à CMP-Neu5Ac
None or Unknown:
General Principles for Synthesis
1: ini&ated by kinase reac&on, consumes 2 NTP example: Glc à Glc-‐6-‐PàGlc-‐1-‐PàUDP-‐Glc
2: mul&ple ways (epimeriza&on, decarboxyla&on, etc.)
example: UDP-‐GlcNAcàUDP-‐GalNAc ; UDP-‐GlcA àUDP-‐Xyl 3: nucleo&de-‐exchange reac&on
example Gal-‐1-‐P +UDP-‐Glc à Glc-‐1-‐P + UDP-‐Gal
Leloir PathwayUDP-Gal/UDP-Glc
AndUDP-GalNAc/UDP-GlcNAc
Interconversion
Galactosemia and potentially CDGs?? (for ‘19 lecture)
Conversion of activated sugar donors
Chapter 4 Figure 2 Essentials of Glycobiology
Second Edition
Generation of UDP-GlcNAc
UDP-GlcNAc as a Nutrient Sensor
GDP-Fuc from GDP-Man UDP-GlcA from UDP-Glc
UDP-Xyl from UDP-GlcA
Reminder: No salvage pathway for GlcA (not clear for Xyl)
CMP-Sialic AcidSynthesis
Glucose is only Sugar Needed for Synthesis of All Sugar Nucleotides
Note: No salvage Pathway for GlcA!
Key Control Points: Early step enzymes that are inhibited by end-‐product Sugar nucleo<de
Transporters for nucleotide sugars
Chapter 4, Figure 4 Essentials of Glycobiology
Second Edition
Getting sugars in cells
Dolichol phosphate: The “other” high energy sugar donor
Chapter 8, Figure 2Essentials of Glycobiology
Second Edition
Dol-P-Man N-link, O-Man, C-Man, GPI anchors
Dol-P-Glc N-linked biosynthesis
Dol-P-GlcNAc N-linked biosynthesis
Generated enzymatically using corresponding sugar
nucleotides (GDP-Man, UDP-Glc, UDP-GlcNAc)…must be “flipped” into lumen of ER
Chapter 4, Figure 1
Biosynthesis and interconversion of monosaccharides
Essentials of Glycobiology Second Edition
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