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
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
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