BIOCHEM2027 Specialised Subject · 4.4
2027 · High School Specialised Subject · Biochemistry

7.4 Carbohydrates as Information Molecules: the Sugar Code

Structural diversity of glycans and SNFG notation, selective recognition by lectins with Kd and avidity, adhesion, trafficking and immunity, microbial attachment, and glycomics methods.

5 SECTIONS20 FIGURESEnglish edition
01

Glycans carry information through structural diversity

  • Glycans differ by sugar type, anomeric configuration, linkage position, chain length, branching and acetylation or sulfation
  • Glycans of identical formula can interact differently with other molecules and therefore carry information
  • Complex glycans are built in the ER and Golgi by enzymes that transfer sugars from nucleotide donors or trim existing chains
  • The final structure depends on cell type, the distribution of glycosyltransferases and glycosidases, donor supply and trafficking
  • The simple idea that one gene determines one glycan therefore fails
  • The phrase sugar code is a metaphor for the whole recognisable structure, not a translation rule like the base sequence
  • SNFG assigns each monosaccharide a shape and colour so that complex structures can be drawn compactly, with blue circles for Glc, yellow for Gal and green for Man
표 7.4-1Features that distinguish glycan structures
Figure 7-65Glycans that differ in arrangement and branching despite identical composition
Figure 7-66Number of orders grows as 2 to the n when two sugars are allowed at each position
Figure 7-67Examples of glycans differing in linkage direction and position
Figure 7-68Guide to simplified SNFG symbols for monosaccharides
02

Lectins recognise glycan structure selectively

  • Lectins are a large class of proteins that recognise and bind glycans, while glycan-binding protein is the broader term covering lectins, antibodies and microbial adhesins
  • Binding rests on hydrogen bonds, dispersion forces, electrostatics, hydrophobic contacts and shape complementarity, and is mostly non-covalent
  • For one site at equilibrium P + L to PL, Kd = [P][L]/[PL] and occupancy theta = [L]/(Kd + [L])
  • A smaller Kd gives higher occupancy at the same concentration, and [L] equals Kd when theta is 0.5
  • Example: Kd 0.50 micromolar with 2.0 micromolar ligand gives theta = 0.80
  • Affinity at a single site and avidity across several sites are separate concepts
  • When several sites engage at once, a broken contact can re-form nearby, which raises total avidity
표 7.4-2Representative lectin families
Figure 7-69Conceptual model of selective glycan recognition and failed binding by lectins
Figure 7-70Relation between Kd and occupancy for a single binding site (theoretical)
Figure 7-71Model comparing monovalent affinity with multivalent avidity
03

Glycan recognition underlies adhesion, trafficking and immunity

  • Leukocytes first roll along the endothelium through weak and repeated binding before reaching an inflammatory site
  • Selectins and glycan determinants on glycoprotein ligands act in this step, while integrins mediate firm adhesion
  • Sialyl Lewis x contains sialic acid and fucose, yet functional selectin binding also depends on how the glycan is presented and on neighbouring sulfated residues
  • ABO antigens arise by adding GalNAc to the H antigen for A and Gal for B, while type O lacks the transferase and keeps H
  • Mannose 6-phosphate marks many lysosomal hydrolases for sorting from Golgi to endosome, though not every lysosomal protein uses only this route
  • The glycocalyx contributes hydration, surface charge, physical contact, receptor accessibility and cell interaction, with composition and thickness varying by cell
Figure 7-72Repeated selectin-glycan binding that contributes to leukocyte rolling
Figure 7-73Simplified terminal sugar difference of ABO antigens, omitting exact stereochemistry
Figure 7-74Typical mannose 6-phosphate-dependent transport of lysosomal enzymes
Figure 7-75Composition and functions of the cell surface glycocalyx
04

Microbes can recognise host surface glycans

  • Viruses and bacteria can use particular host glycans as attachment targets
  • Attachment influences the first stage of infection, but protein receptors, host defence and tissue environment also determine whether infection establishes
  • Binding to a glycan does not by itself establish infectivity or virulence
  • Influenza haemagglutinin recognises sialylated glycans, with human-adapted lineages tending toward alpha2,6 and avian lineages toward alpha2,3 linkages
  • Lineage and variant properties vary widely, so linkage preference alone does not fix host range
  • Decoy molecules that mimic the receptor are under study, but binding in vitro does not guarantee a therapeutic effect
Figure 7-76Principle of pathogen attachment and host surface glycan specificity (concept, not an infection experiment)
Figure 7-77Comparison of alpha2-3 and alpha2-6 sialic acid linkages
Figure 7-78Competitive binding of compounds that mimic a receptor glycan
05

Glycomics methods and data interpretation

  • Mass spectrometry gives molecular mass and fragment ions, and combining it with chromatography, specific glycosidases, labelling and linkage analysis strengthens the case
  • Equal composition can still differ in branching and linkage, so equal mass does not fix structure
  • Lectin microarrays immobilise lectins while glycan microarrays immobilise glycans, and both compare selective binding signals
  • Either format requires control of background, non-specific binding, sample amount, labelling, concentration and layout
  • Example: readings of 0.90, 0.95 and 0.84 for G4 give a mean of 0.897, and 0.78, 0.86 and 0.75 for G2 give a sample standard deviation of 0.057
  • Reproducibility alone does not prove specificity, so negative controls and competition experiments are needed
  • One chromatographic peak does not imply a single chemically pure structure
표 7.4-3Controls for glycan array experiments
Figure 7-79Main stages of glycan analysis and why mass alone does not fix structure
Figure 7-80Simulated fluorescence signals from a replicated glycan microarray (not measured data)
Figure 7-81Mean and sample standard deviation of three simulated microarray measurements
Figure 7-82Simulated chromatogram representing separation of a glycan population
Figure 7-83Teaching diagram of the difference between similar composition and equivalent structure
Figure 7-84Integrated flow of the main glycomics concepts in unit 7
2027 High School Specialised Subject · Biochemistry · Sangil Park (Asan High School) · Reference material is printed as an appendix.
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