45. Glycoproteins and lysosomal diseases

Question 1

Glycoproteins

Answer 1

short carb-chain + protein.

Includes collagens, mucins, transport molecules, immunoglobins, hormones, fibronigen, lectin.

Question 2

Glycoprotein- O-linked

Answer 2

Collagen: between glucose/galactose and hydroxylysine

Others :between N-acetylgalactoamine and serine/threonine

Question 3

Glycoprotein - N-linked

Answer 3

Between N-acetylglucoamine and asparagine.

Simple (high mannose) or complex (mannose + galactose, fucose, NANA and N-acetylglucoamine) side chains.

Question 4

Proteoglycans

Answer 4

protein + long carb chain.

Includes ECM components, heparin, some lubricants and transporters

Question 5

Proteoglycans: glycoaminoglycans

Answer 5

Disaccharide motifs-gal-gal-xyl-SERINE
Includes hyaluronic acid (no sulfate), chondriotin sulfate, dermatan sulfate, heparan sulfate, haparin (most sulfate) and keratan sulfate

Question 6

Proteoglycan polymers

Answer 6

Proteoglycan monomers are non-covalently linked to hyalurnoic acid through linker proteins in “bottle brush” arrangements

Question 7

Synthesis of glycoproteins and proteoglycans

Answer 7

Saccharide chains: NDP-activated carbs are added by specific glycocyltransferases (CMP-NANA)
O-linked glycoaminoglycans are added directly one by one.
N-linked glycoaminoglycans are pre-assembled then added.

Question 8

Degradation of proteoglycans and glycoproteins

Answer 8

hydrolytic enzymes in lysosomes take each molecule off in last-on-first-off basis.

Question 9

I-cell disease

Answer 9

Lack of targeting signal (mannose6P) in lysosomal enzymes lead to deficiency in lysosomal enzymes in lysosome while the enzymes are secreted.
Fibroblasts have dense inclusion bodies (I-cells)

Sx: corneal clouding, dysostosis multiplex, mental retard, HM, cardioM, URI, death in infancy

Question 10

Type I lysosomal disease

Answer 10

Hurler.
Defective iduronidase
Dermatan&heparan sulfates accum.
Clouding of cornea, mental, dysostosis

Question 11

Type II lysosomal disease

Answer 11

Hunter–X-linked
Defective iduronate sulfatase
Dermatan and heparan sulfate accum.
NO corneal clouding, milder than type I

Question 12

Type III A&B lysosomal disease

Answer 12

Sanfillipo A&B
Heparan-n-sulfamidase or N-acetyl-glucosaminidase
Heparan accum.
Severe CNS but little somatic sx.

Question 13

Type IV

Answer 13

Morquio
Hexosamine 6-sulfatase
Keratan sulfate accum.
Severe somatic and bone sx. Little CNS