 Differences between glycoproteins and

proteoglycans
 Functions and structures of glycoproteins and
proteoglycans
 Synthesis and degradation of glycoproteins and
proteoglycans
 Pathology related to glycoproteins and
proteoglycans
 Proteins conjugated to
Glycoproteins saccharides lacking a
Protein>>carbohydrate
serial repeat unit

Proteoglycans Proteins conjugated to Carbohydrate>>protein

polysaccharides with
serial repeat units

Glycosaminoglycans Repeat unit

Mucopolysaccharides HexN and HexUA
These molecules function in the extracellular matrix (ECM)
Overview of glycoproteins:
--carbohydrate chain short
--no serial repeats
--often branched, not linear
--variable amounts of carbs
--wide range of functions
 Some Functions of Glycoproteins
_________________________________________________
Function Glycoprotein
_________________________________________________
1. Structural molecule Collagens
2. Lubricant Mucins
3. Transport molecule e.g. Transferrin,
Ceruloplasmin
4. Immune system Immunoglobulins,
Histocompatibility antigens,
Blood group determinants
5. Hormone e.g. HCG, TSH
6. Enzymes e.g. Alkaline phosphatase
7. Blood clotting e.g. Fibrinogen
8. Cell surface recognition Lectins
__________________________________________________
One or more carbohydrate chains--covalently linked to a
protein.
The chains may be neutral or negatively charged. They are
frequently branched.

There are two types of glycosidic links:

1. O-glycosidic link
O-glycosidic link between galactose or glucose and the hydroxyl
group of hydroxylysine (i.e. collagen).
Other O-linked glycoproteins have a glycosidic link between N-
acetyl galactosamine and either serine or threonine (i.e. blood
group substances and salivary mucins).
2. N-glycosidic link
N-glycosidic links exist between N-acetylglucosamine and
asparagine. There are two types:
A. High mannose
B. Complex. For example, in addition to mannose they may
contain N-acetylglucosamine, galactose, fucose and N-
acetylneuraminic acid (sialic acid)
Lippincott
SYNTHESIS OF GLYCOPROTEINS

Synthesized on ribosomes attached to the RER, then

transported via vesicles to the Golgi for sorting

The units in the saccharide chains are added from

UDP-glucuronic acid, UDP-N-acetylgalactosamine and
GDP-mannose.
Sialic acid in glycoproteins is added from CMP-NANA.
These additions are catalyzed by specific
glycosyltransferases.

For synthesis of O-linked glycoproteins, addition is direct.

For N-linked glycoproteins, the chain is formed on
dolichol pyrophosphate and then transferred to the
protein.
DEGRADATION OF GLYCOPROTEINS

Degradation of the saccharide chains is achieved

by hydrolytic enzymes present in lysosomes.
The enzymes act on the ends of the chains on a
last-on-first-off basis.

Defects can lead to a number of

diseases/disorders
 I-cell disease results from an enzyme
deficiency so that lysosomal enzymes do not
aquire the targeting signal, mannose 6-
phosphate.
 Fibroblasts in this disease have dense
inclusion bodies (I-cells) and are deficient in
many lysosomal enzymes.
 The lysosomes become engorged with
indigestible substrates, leading to death in
infancy.
Proteoglycans are usually
structural components of the
extracellular
matrix; some have a lubricant
role.
--bind large amounts of water
--cell/cell signalling and adehsion
roles

Heparin is normally intracellular

and it inhibits blood clotting.
SYNTHESIS OF PROTEOGLYCANS
Synthesized in Golgi

The units in the saccharide chains are elongated in

alternating acidic/amino sugars, donated from UDP
derivatives. Last step is sulfation of some amino sugars.

For glycosaminoglycan synthesis and synthesis of O-linked

glycoproteins, the addition is direct.
For N-linked glycoproteins, the chain is formed on
dolichol pyrophosphate and then transferred to the
protein.
DEGRADATION OF PROTEOGLYCANS

Some proteoglycans must be phagocytosized first

Degradation of the saccharide chains is achieved

by hydrolytic enzymes present in lysosomes.
The enzymes act on the ends of the chains on a
last-on-first-off basis.

Defects can lead to a number of

diseases/disorders
Rare inborn errors in the degradation of glycosaminoglycans
result in a series of diseases called mucopolysaccharidoses;
characterized by mental retardation and/or structural defects.

MPS Type I
Hurler’s syndrome results from a deficiency of alpha-L-
iduronidase. Heparan sulfate and dermatan sulfate accumulate.
There is growth and mental retardation with characteristic
facial changes.
MPS Type II
Hunters syndrome is similar to Hurler’s syndrome but the
enzyme deficiency is for iduronate sulfatase and the inheritance
is X-linked.
MPS Type III
Sanfilipo’s syndrome is caused by a deficiency of one of four
enzymes of which three are hydrolases and one is an N-
acetyltransferase. There is severe mental retardation but only
mild structural features.

Other MPS Types are IV, VI and VII. There is no MPS Type V.
MPS I (Hurler
Syndrome)

A deficiency of L-
iduronidase leads to
mental retardation and
structural changes due
to accumulation of
dermatan sulfate and
heparan sulfate
MPS II (Hunter Syndrome)
X-linked disease due to a
deficiency of iduronate
sulfatase
MPS III (Sanfilippo Syndrome)

Deficiency in one of four

degradative enzymes leads to
severe mental retardation but
little structural change
MPS IV (Morquio Syndrome)
Deficiency of a galactose-6-sulfatase or a beta-
galactosidase leads to accumulation of keratan sulfate
with normal intelligence but severe deformity
Summary

Glycoproteins and proteoglycans are distinct:

--functions/structures
--synthesis/degradation
--associated pathologies