The document discusses glycoproteins, which are proteins with attached oligosaccharide chains, and their biochemical roles, types, and mechanisms of glycosylation. It outlines the differences between O-linked and N-linked glycoproteins, their synthesis, and associated diseases such as Hematopoietic System Dysfunction, Leukocyte Adhesion Deficiency, and Paroxysmal Nocturnal Hemoglobinuria. Additionally, it highlights the impact of glycoproteins on various congenital disorders of glycosylation affecting multiple organ systems.

1. Glycoproteins
(N & O glycosylation)

2. • Objectives
• Glycoproteins
• Biological role of glycoproteins
• Glycosylation
• Disease

3. Glycoproteins
• They are proteins that contain oligosaccharide
(glycan) chains covalently attached to their
polypeptide backbones.
• Eight sugars predominate in human
glycoproteins
• Glucose, Galactose, Mannose, N-Acetyl
neuraminic acid, Fucose, N-Acetylgalactosamine,
N-Acetylglucosamine, Xylose .

4. Functions Served by Glycoproteins

5.  Classes of Glycoproteins:
 O-Linked
Glycoproteins
GalNAcSer(Thr)
linkage
GlcNAc-Ser[Thr]
linkage
 N-Linked
Glycoproteins
Amide nitrogen of asparagine and Nacetylglucosamine (GlcNAcAsn)
 GPI-Linked
Glycoproteins

6.  O-glycosidic linkage-hydroxyl side chain of serine or threonine and a
sugar such as Nacetylgalactosamine (GalNAc-Ser[Thr])
 N-glycosidic linkage-amide nitrogen of asparagine and Nacetylglucosamine
(GlcNAcAsn)
 Glycosylphosphatidylinositol-anchored
(GPI-anchored, or GPI-linked)- carboxyl terminal amino acid of a
protein via a phosphoryl-ethanolamine moiety joined to an oligosaccharide
(glycan), which in turn is linked via glucosamine to phosphatidylinosito

7. O-linkage
(N -acetylgalactosamine to serine)

8.  N-linkage
(N -acetylglucosamine to asparagine

9. DIFFERENCES BETWEEN O- & N- LINKED
GLYCOPROTEINS:

N-Linked Glycoproteins
Synthesis:-
• Cotranslationally
• En-bloc transfer of
Oligosachharide chain on
the protein and further
modification.
• Enzymes not membrane
bound.
• Dolichol P-POligosaccharide involved.
• Inhibited by Tunicamycin
 O-Linked Glycoproteins
Synthesis:-
• Post- translationally
• Oligosaccharide chain
synthesized on the protein.
• Enzymes membrane bound.
• Dolichol not involved.
• Not inhibited by Tunicamycin

10. SOME DISEASES DUE TO GLYCOPROTEINS:
Disease
HEMPAS
Leukocyte adhesion deficiency, type II
Paroxysmal nocturnal hemoglobinuria
I-cell disease
Congenital disorders of glycosylation

11.  HEMPAS:
 Hereditary Erythroblastic Multinuclearity With A Positive Acidified
Lysis Test .
 Also known as Congenital Dyserythropoietic Anemia Type II.
 Claimed to be due to defects in alpha–mannosidase II
 Characterized by
– Ineffective erythropoiesis
– Hemolysis & erythroblast morphological abnormalities
– Hypoglycosylation of some red blood cell (RBC) membrane proteins.
 Treatment consists of frequent blood transfusions and chelation
therapy

12.  Leukocyte adhesion deficiency (LAD)
 A congenital disorder of glycosylation
 Mutations affecting the activity of a Golgi-located GDP-fuc
transporter
 Marked decrease in neutrophil rolling
 Subjects suffer
– Life-threatening, recurrent bacterial infections
– Psychomotor and mental retardation
 The condition appears to respond to oral fucose

13.  Paroxysmal Nocturnal Hemoglobinuria:

14. I-CellDisease:

15.  Congenital Disorder of Glycosylation
Previously called carbohydrate-deficient glycoprotein
syndrome.
 Glycosylation of a variety of tissue proteins and/or lipids is
deficient or defective.
 CDG-I mainly in ER & related to steps prior processing of
glycan chains and transfer of oligosac chain to protein.
 CDG-II includes all defects localized in the processing of Nglycans on the
glycosylated protein. These are situated mainly
in the Golgi compartment.
 Often cause serious, sometimes fatal, malfunction of several
different organ systems (especially the nervous system,
muscles, and intestines) in affected infants