Glycobiolgy 1

Question 1

GAGs can be classified based on 3 characteristics, what are they

Answer 1

Monomeric composition
Type of glycosidic linkages
Location of sulfate units

Question 2

What are the three types of acidic sugars?

Answer 2

Glucuronic acid
Iduronic acid
Galactose

GIG

Question 3

Three types of amino sugars

Answer 3

N-Acetylgalactosamine
N-acetylglucosamine
Glucosamine

NNAAG

Question 4

Chondroitin 4 and Chondroitin 6 sulfate

Answer 4

Most abundant GAG in the body. Found in cartilage, tendons, ligaments, and aorta

Question 5

Dermatan Sulfate

Answer 5

In the skin, blood vessels, and heart valves

Associated with hunter disease, hurler disease, sanfilippo disease, and sly disease

Question 6

Keratin sulfate I and II

Answer 6

Has a beta1,4-glycosidic linkage
— as opposed to the usual 1,3

I - mostly in the cornea
II - mainly in connective tissues

Associated with morquio syndrome A and B

Question 7

Heparin/heparan sulfate

Answer 7

Heparin - anticoagulant
- involved with intracellular mast-cells lining arteries especially the liver, lungs , and skin

Associated with hunter disease, hurler disease, sanfilippo, and sly disease

Question 8

Hyaluronic acid

Answer 8

No sulfate is the distinguishing feature
Not limited to animals
Acts as a lubricant, shock absorber, synovial fluid in joints, vitreous humor of eye, umbilical cord, loose connective tissue and cartilage

Question 9

Structure of proteoglycan monomers

Answer 9

Except for Hyaluronic acid, they are all covalently bound to proteins.
The connection to the core protein is as follows: connected to the core protein is a serine side chain, and then there is a linker region made up of xylose, galactose, galactose. Then finally we have the repeating dissacharide unit.

Question 10

Where are most cytoplasmic proteins synthesized?

Answer 10

Free standing cytosolic ribosomes

Question 11

Where are most integral membrane, cell surface, lysosomal, extracellular, or secreted proteins synthesized?

Answer 11

On ribosomes attached to the RER and then extruded into the lumen

Question 12

What is the optimal ph for lysosomal enzymes? Why

Answer 12

Around 5. This way In the neutral cytosol they won’t do much damage if there is a leaky lysosome.

Question 13

What is the half life of GAGs?

Answer 13

3-10 days

Question 14

How are GAGs degraded?

Answer 14

Because gags are extracellular or pm cell surfaces, they are just phagocytized and then fuse with a lysosome - very efficient
Endoglycosidases first cleave polysaccharide chains into oligosaccharides
From there, the oligosaccharide is degraded sequentially from the non-reducing end of the chain. Therefore, the last one to be put on will be the first one degraded.

Question 15

Mucopolysaccharidoses

Answer 15

Autosomal recessive diseases (except hunter)
Progressive disease that causes deterioration over time
Caused by any one of the lysosomal hydrolases involved I he degradation of heparan sulfate or dermatan sulfate
Presence of oligosaccharides in urine

Question 16

Hunter

Answer 16

Iduronate sulfatase deficiency
Affects degradation of dermatan sulfate, heparan sulfate
Symptoms: physical deformity and mental retardation

Question 17

Hurler

Answer 17

Alpha-L-Idurodianse deficiency
Affects degradation of dermatan sulfate, heparan sulfate
Symptoms: corneal clouding, dysmorphic facial features, upper airway obstruction, hearing loss, deposition in coronary artery may lead to ischemia And early death

Question 18

Sanfilippo

Answer 18

Affects the degradation of heparan sulfate

Symptoms: severe nervous system disorders, profound mental retardation

Question 19

What are the two categories of glycoproteins?

Answer 19

N or O glycoproteins

Question 20

Synthesis Fo O-linked glycoside

Answer 20

Synthesized in the rough ER and then extruded into the lumen and transported to the Golgi.
Glycosylation then occurs onto the serine or threonine residue.
Oligosaccharide chain extension involves specific glycotransferases that add nucleotide sugar residues to the previously bound sugar

Question 21

Synthesis of N-linked glycoside

Answer 21

Begins in the RER, branched oligosaccharide is synthesized on dolichol pyrophosphate. It is then transferred onto an asparagine residue of a growing polypeptide chain. It is continually trimmed on the RER and the Golgi

Question 22

How does transport of n linked glycoproteins to lysosomes work?

Answer 22

There is a specific phosphotransferase that phosphorylates mannose6-phosphate residues of the N-linked oligosaccharide

• acid hydrolases in the lysosome contribute to the breakdown of substances
• without the phosphorylated M6P, the acid hydrolases are instead secreted
• this leads to a substance build up in the lysosomes and the I-cell phenotype

Question 23

I cell

Answer 23

Skeletal abnormalities
Restricted joint movement
Dysmorphic facial features
Severe psychomotor impairment

• high concentrations of acid hydrolases in the blood instead of exclusively in the lysosome

Question 24

Molecular structure of GAGs

Answer 24

Repeating disaccharides units of one acidic and one amino sugar.
Amino group is usually acetylated so it neutral charged
Heteropolysaccharide chains repel each other due to the negative charges
When brought together the chains slip past each other giving rise to the general slippery consistency