Glycans

Glycans

1. History

   • Historical Roles
     • Targeting signals
     • Cancer progression
     • Reaggregation of sponge cells
     • Mediating proteins
     • Energy production and metabolism
   • Knowledge lag in the study of function
     • More rapidly evolving
     • Diverse and complex
   • Study of genetic alterations in glycosylation in various organisms
     • Discovery of genetic defect in I-cell disease
     • Defect in PAPS formation
     • deficiency of a glycosaminoglycan core galactosyltransferase
     • Knocking out class or subclass of glycan is fatal, altering outer sugars gives living organism with species-specific defects

2. Important examples in vertebrates

   • Sialic acid
     • Sialoadhesins, or siglecs, are lectin proteins that bind to it
     • Modulates function of certain proteins
   • Mannose
     • Intraorganismal target signalling
   • Mannose 6-phosphate
     • Intraorganismal target signalling
     • Mediates transport of enzymes to locations in the lysosome
   • Heparin
     • Interacts with antithrombin
     • Anticoagulant effect

3. I-cell disease

   • Genetic defect in this disease proved the biological importance of the mannose 6 phosphate targeting pathway
   • Inhibits body's ability to break down fats
   • Causes low muscle tone, developmental delay, and some physical abnormalities.

4. Glycoproteins

   • Lectins
     • Bound by glycans which mediate their function
   • Selectins
     • Cell adhesion molecules
     • Play a crucial role in leukocyte trafficking
   • Galectins
     • Found in animals
     • Facilitates crosslinking of the ECM in animals
   • Other types of lectins
     • R - signal targeting, glycoprotein hormone turnover
     • L protein sorting
     • P - protein sorting, signal targeting, degradation of glycoproteins
     • C - cell adhesion, glycoprotein clearance and innate immunity

5. Glycosylation

   • Most common form
     • Nucleocytoplasmic modification
     • O-type glycosylation
   • Congenital disorders
     • multisystem disorders caused by enzymatic and genetic defects