mucopolysaccharides

1. 1
ANJU ANTHARJANAM V.S.
S2 Msc.Biochemistry
Dept.of Biochemistry
University of Kerala
Kariavattom campus

2. • Carbohydrates can be classified based on the
number of monomers.
– Mono-
– Oligo-
– Polysaccharides
• Carbohydrates associates with proteins.
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 GAGS
Proteo-
glycans
Glyco-
proteins

3. Heteroglycans
made up of
repeating units of
sugar derivatives
namely amino
sugars and uronic
acids.
Glycosaminoglycans
(GAG)
SULFATE
GROUPS
CARBOXYL
GROUPS
ACID MUCOPOLYSACCHARIDESNEGATIVE CHARGE
N- Acetyl Glucosamine/ N- Acetyl Galactosamine
D-Glucuronic acid/L-Iduronic acid.
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4. POLYMER REPEATING UNITS SIGNIFICANCE
Hyaluronic acid D-Glucuronic acid, N- Acetyl
Glucosamine.
Lubricant ,vitreous humor
consistency,ECM of cartilage
& tendons.
Chondroitin sulfate D-Glucuronic acid, N- Acetyl
Galactosamine 4-sulfate.
Tensile strength
Dermatan sulfate L-Iduronic acid. ,N- Acetyl
Galactosamine 4-sulfate.
Pliability of skin
Heparin N-Sulfo D-glucosamine 6-
sulfate,glucuronate 2- sulfate.
anticoagulant
Keratin sulfate D-Galactose,N-Acetyl
glucosamine 6-sulfate.
keeps cornea transparent
Some Important GAGs.
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5. Protein-carbohydrate Associations…
Carbohydrate > protein = proteoglycan
Carbohydrate < protein =Glycoprotein
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6. BIOSYNTHESIS
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7. Nucleotide Linked Sugars !!!
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GLYCOSYL
DONORS

8. UDP - Galactose Formation !
• UDP-Galactose 4-epimerase catalyzes
epimerization of UDP-Glucose to UDP-
Galactose.
• UDP-Galactose is also derived from free
galactose.
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9. Formation of N- Acetyl Glucosamine.
• Transamidation.
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10. Synthesis Of N- Acetyl Galactosamine
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11. Formation of D-Glucuronic acid.
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12. Formation of Iduronic acid
• The epimerization of D-Glucuronic acid to L-
Iduronic acid occurs after incorporation into
the polymer chain and is coupled with the
process of sulfation.
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13. Biosynthesis Of Gags…
• Mostly are synthesised as polymers attached
to proteins.
• Major steps are:
– Formation of linkage saccharide chain
– Initiation by glycosyl transferases and elongation.
– modifications--- sulfation, acetylation etc..
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14. HYALURONIC ACID
• Co-polymer of D-Glucuronic acid, N- Acetyl
Glucosamine.
• It is unsulfated.
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16. CHONDROITIN SULFATE
• Co-polymer of D-Glucuronic acid and N- Acetyl
Galactosamine 4-sulfate.
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17. DERMATAN SULFATE
• Co-polymer of L- Iduronic acid and N- Acetyl
Galactosamine 4-sulfate.
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18. • Chondroitin sulfate and dermatan sulfate are
synthesized as galactosaminoglycan polymers
containing N-acetylgalactosmine alternating with
glucuronic acid. Epimerization of any of the
glucuronic acid residues to Iduronic Acid at the
polymer level constitutes the formation of
dermatan sulfate.
• Chondroitin/dermatan glycosaminoglycans are
covalently attached by a common tetrasaccharide
sequence to the serine residues of core proteins.
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19. KERATAN SULFATE
• Co-polymer of D-Galactose and N-Acetyl
glucosamine 6-sulfate.
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20. • Keratan sulfate chain elongation is initiated at the
nonreducing terminus of oligosaccharides that link
the polymer to protein.
• Extension of the keratan sulfate chain occurs via the
action of glycosyltransferases that alternately add Gal
and GlcNAc to the growing polymer. Extension of
keratan sulfate involves transfer of both β-4-
galactose and β-3-N-acetylglucosamine to the
growing chain.
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21. • Sulfation of keratan sulfate occurs with the
help of sulfotransferases.
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23. HEPARIN
• Co-polymer of N-Sulfo D-glucosamine 6-
sulfate and glucuronate 2- sulfate.
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24. Biosynthesis….
• Many different cell types produce HS chains with many different
primary structures.
• enzymes consist of multiple glycosyl transferases,sulfotransferases
and an epimerase.
• HS synthesis initiates with the transfer of xylose from UDP-xylose by
xylosyltransferase(XT) to specific serine residues within the protein
core. Attachment of two galactose (Gal) residues by
galactosyltransferases I and II (GalTI and GalTII) and glucuronic acid
(GlcA) by glucuronosyltransferase I (GlcATI) completes the
formation of a core protein linkage tetrasaccharide.
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25. • After attachment of the first N-
acetylglucosamine(GlcNAc)
residue elongation of the
tetrasacchride linker is
continued by the stepwise
addition of GlcA and GlcNAc
residues. These are transferred
from their respective UDP-
sugar nucleotides.
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27. PROTEOGLYCANS
• Proteins are attached to a particular type of
polysaccharides called Glycosaminoglycans.
• Their properties are primarily determined by
the glycosamine content.
• Joint lubricants, structural components in CT..
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30. • A carbohydrate group can be covalently
attached to a protein to form a glycoprotein.
• Carbohydrate < protein =Glycoprotein
• They are components of cell membranes and
have role in cell adhesion.
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31. Linkage Through Asparagine (N-linked) Or
Through Ser/ Thr (O-linked).
• Sugars in glycoproteins are attached either to
the amide nitrogen atom in the side chain of
asparagine (termed an N-linkage) or to the
oxygen atom in the side chain of ser or
thr(termed an O-linkage).
• An asparagine residue can accept an
oligosaccharide only if the residue is part of an
Asn –X-Ser or Asn-X-thr sequence in which X
can be any residue except proline.
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32. • All N-linked oligosaccharides have in common
a pentasaccharide core consisting of three
mannose and two N-acetylglucosamine
residues.
• All other sugars are attached to this core to
form great variety of oligosaccharide patterns
found in glycoproteins.
• Glycosyltransferases
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33. Site of glycosylation..
• Protein glycosylation takes place inside the lumen
of the ER and in the Golgi complex.
• The protein is synthesised by ribosomes attached
to the cytoplasmic face of the ER membrane and
the peptide is inserted into the lumen of ER.
• The N-linked glycosylation begins in the ER and
continues in the golgi complex.
• O-linked glycosylation takes place exclusively in
the golgi complex.
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34. Involvement Of Dolichol Phosphate
• Dolichol phosphate (DP) is a specialized lipid
molecule located in the ER membrane and
contain about 20 isoprene units.
• The terminal phosphate group is the site of
attachment of the activated oligosaccharide
which is subsequently transferred to a specific
asparagine residue of the growing polypeptide
chain.
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35. • Oligosaccharyl transferase is the
enzyme responsible for the
recognition of the consensus
sequence and the transfer of the
precursor glycan to a polypeptide
acceptor which is being translated in
the endoplasmic reticulum lumen.
N-linked glycosylation is therefore, a
co-translational event.
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38. O-linked glycosylation N-linked glycosylation
Post transationally Co-trasitionally
No DP DP is involved
Oligosacchride chain synthesised
on protein
Oligosaccharide chain transferred
to protein
Enzymes are membrane bound Enzymes are not membrane
bound
Difference between..
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39. REFERENCES
Metabolism Of Acid Mucopolysaccharides,
Albert Dorfman.
Textbook Of Biochemistry With Clinical
Correlations by Thomas M.Devlin.
Biochemistry by Lubert Stryer Et.Al.,(6th
Edition).
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