Presentation on theme: "ESSENTIALS OF GLYCOBIOLOGY LECTURE 4 MONOSACCHARIDE METABOLISM AND SUGAR NUCLEOTIDE TRANSPORTERS Hud Freeze."— Presentation transcript:
ESSENTIALS OF GLYCOBIOLOGY LECTURE 4 MONOSACCHARIDE METABOLISM AND SUGAR NUCLEOTIDE TRANSPORTERS Hud Freeze
INTRODUCTION Traditional Approach--Study the enzymes and substrates in cells Holistic Approach--Add homeostasis and disease considerations Glucose is the central player, but not the only player Monosaccharides = sugars First Principles Meet the players Source of sugars: Transport into cells salvage them make them in cells Activate the sugars Deliver activated sugars to the proper location
Glc Man Gal GalNAcGlcNAc Fuc GlcA Xyl Sia THE SUGAR LEAGUE Fru-6-P
UDP-Glc + Gal-1-P Glc-1-P + UDP-Gal X Galactosemia Inability to metabolize Galactose--potentially lethal Treatment: Galactose restricted diet Even with proper diet: patients have dyspraxic speech, ovarian failure, poor growth, neurological impairment Knockout mouse does not have disease phenotype! Other genes important
Mannose supplements can treat a human disorder: Fru-6-P-->Man-6-P
Oral fucose supplements used to treat a human genetic disorder
?s These are the Major Leaguers, how about life in the Minors?
BIOSYNTHESIS OF UNUSUAL SUGARS KDN--2-keto-3-deoxy-D-glycero-D-galactonononic acid a sialic acid analog found mostly in fish eggs Man--->Man-6-P---> KDN---> CMP-KDN + + PEPCTP Glycoproteins, glycolipids Galactofuranose--Galf, found in bacteria and lower eukaryotes pf UDP-Galp---->UDP-Galf----> Glycoconjugates mutase Galactofuranosyl transferases
From: Schenk et al Glycobiol 11, 61R, 2001 SYNTHESIS OF DOLICHYL PHOSPHATE
All of the precursors are made in the cytoplasm or nucleus-- BUT, most glycoconjugates are made in the Golgi or ER
SUMMARY AND TAKE HOME MESSAGES Glucose can be made into all sugars (monosaccharides) All sugars require activation and most require transport of the activated forms Transporters deliver the sugars to cells Salvaged and imported sugars can contribute to glycoconjugate synthesis The relative contributions of each source may be cell/tissue specific Some disorders in sugar metabolism can be treated with dietary modifications Hard to know specificity of sugar nucleotide and monosaccharide transporters Sugar is good for you---mostly
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