7.3 Glycoconjugates · Biochemistry 2027

Proteoglycans carry GAG chains at the cell surface and in the matrix

Glycoconjugates are molecules in which glycans are joined to proteins or lipids
Glycan structure is set by sugar type, linkage position, branching, terminal sugar and sulfation
A proteoglycan is a core protein carrying covalently attached GAG chains
GAGs are repeating disaccharides of an amino sugar with a uronic acid or galactose, and carboxylate and sulfate charges support hydration and compression resistance
Chondroitin and heparan sulfate attach through serine to xylose, two galactoses and glucuronic acid
That linkage cannot be generalised to every GAG
Aggrecan carries many chondroitin and keratan chains and binds hyaluronan non-covalently to form large aggregates
Example: with 20 repeats each carrying one carboxyl and 0.8 sulfate the mean formal charge is about -20 x 1.8, that is -36

GAG amount reflects a balance of biosynthesis, degradation and extracellular traffic
Defects in glycosyltransferases or sulfotransferases change chain length or sulfation and affect tissue formation and signalling
Deficiency of lysosomal hydrolases or sulfatases lets GAG fragments accumulate
MPS I results from reduced alpha-L-iduronidase activity through IDUA variants, impairing breakdown of dermatan and heparan sulfate
Undegraded GAG accumulates in lysosomes and affects many tissues, with highly variable clinical features
The model dM/dt = P - kM gives M* = P/k, so P = 6 with k = 0.30 gives 20 units and k = 0.10 gives 60
Those values are a teaching model, not measured patient data

A glycoprotein carries glycans covalently attached to protein
N-linked glycosylation attaches GlcNAc to the amide nitrogen of asparagine, with the candidate sequon Asn-X-Ser/Thr where X is usually not proline
A sequon alone does not guarantee glycosylation, since accessibility, structure and localisation also act
O-linked mucin-type glycosylation starts with GalNAc on the hydroxyl of Ser or Thr
Glycosylation is enzymatic, whereas glycation is the non-enzymatic reaction of a reducing sugar with protein
Glycans support folding quality control, secretion, stability and recognition, and the many O-linked chains of mucin favour lubrication and protection
Signals at 28.0 and 31.2 kDa in mass data suggest a difference of about 3.2 kDa in glycan content

A glycolipid carries glycan on a lipid, and in animal cells the glycosphingolipids built on ceramide are the main example
Gangliosides are glycosphingolipids containing at least one sialic acid
ABO antigens differ in terminal sugar: adding GalNAc to the H antigen gives A and adding Gal gives B
Type O usually retains the H antigen because the transferases that add the A or B terminal sugar are inactive
Gram-negative lipopolysaccharide is lipid A for membrane anchoring plus a core oligosaccharide and the O antigen polysaccharide
LPS and animal glycosphingolipids have different membrane anchors and cannot be placed in one family

The formal charge model for a GAG is Q = -n x (1 + s), where n is the number of repeats and s the mean sulfates per repeat
With 20 repeats and 0.5 sulfate per repeat Q = -20 x 1.5 = -30
The model ignores ionic strength, counterions and steric constraints, so it does not map one-to-one onto real charge, hydration or viscoelasticity
In scanning for N-X-S/T the window with proline at X is excluded, and candidates are not guaranteed to be glycosylated
The number of attached glycans changes mass and glycan mass fraction, and apparent electrophoretic mass can differ from mass spectrometry
One sequence gives several glycoforms through site occupancy, branching and cell-type-specific enzyme expression

References

**표 7.3-1**The four families of glycoconjugates
Family	Composition and linkage	Examples	Main function
Proteoglycan	Core protein with long GAG chains	Aggrecan, syndecan	Hydration, compression resistance, signalling
Glycoprotein	Protein with N- or O-linked oligosaccharides	Mucin, antibodies, membrane receptors	Recognition, folding, protein trafficking
Glycolipid	Lipid anchor with outward glycan	Glucosylceramide, GM1	Membrane recognition, signalling, membrane properties
Lipopolysaccharide	Lipid A with core sugar and O antigen	Gram-negative outer membrane	Barrier function and immune recognition

**표 7.3-2**A simple model of GAG accumulation
Term	Normal model	Reduced degradation	Interpretation
Production rate P	6 units per day	6 units per day	Unchanged
Degradation constant k	0.30 per day	0.10 per day	Falls to one third
Steady state M*	20 units	60 units	Threefold rise

**표 7.3-3**N-linked and O-linked glycosylation compared
Feature	N-linked	O-linked (mucin type)
Linked residue	Asparagine (Asn)	Serine or threonine
First sugar	GlcNAc	GalNAc
Initial synthesis	Assembled on a lipid carrier in the ER then transferred	Usually added stepwise in the Golgi
Typical function	Folding quality control, secretion, recognition	Mucus formation, lubrication, surface protection
Caution	Asn-X-Ser/Thr is only a candidate and is not always glycosylated	Not every O-linked glycan is mucin type

**표 7.3-4**Animal glycosphingolipids and bacterial LPS
Feature	Animal glycosphingolipid	Bacterial lipopolysaccharide
Membrane anchor	Ceramide	Lipid A
Typical location	Non-cytosolic leaflet of animal membranes	Outer leaflet of the Gram-negative outer membrane
Glycan structure	Various oligosaccharides on ceramide	Core sugar with repeating O antigen
Biological role	Cell recognition, signalling, membrane organisation	Barrier function, surface diversity, immune recognition