Glycobiolgy 1 Flashcards
GAGs can be classified based on 3 characteristics, what are they
Monomeric composition
Type of glycosidic linkages
Location of sulfate units
What are the three types of acidic sugars?
Glucuronic acid
Iduronic acid
Galactose
GIG
Three types of amino sugars
N-Acetylgalactosamine
N-acetylglucosamine
Glucosamine
NNAAG
Chondroitin 4 and Chondroitin 6 sulfate
Most abundant GAG in the body. Found in cartilage, tendons, ligaments, and aorta
Dermatan Sulfate
In the skin, blood vessels, and heart valves
Associated with hunter disease, hurler disease, sanfilippo disease, and sly disease
Keratin sulfate I and II
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
Heparin/heparan sulfate
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
Hyaluronic acid
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
Structure of proteoglycan monomers
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.
Where are most cytoplasmic proteins synthesized?
Free standing cytosolic ribosomes
Where are most integral membrane, cell surface, lysosomal, extracellular, or secreted proteins synthesized?
On ribosomes attached to the RER and then extruded into the lumen
What is the optimal ph for lysosomal enzymes? Why
Around 5. This way In the neutral cytosol they won’t do much damage if there is a leaky lysosome.
What is the half life of GAGs?
3-10 days
How are GAGs degraded?
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.
Mucopolysaccharidoses
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
Hunter
Iduronate sulfatase deficiency
Affects degradation of dermatan sulfate, heparan sulfate
Symptoms: physical deformity and mental retardation
Hurler
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
Sanfilippo
Affects the degradation of heparan sulfate
Symptoms: severe nervous system disorders, profound mental retardation
What are the two categories of glycoproteins?
N or O glycoproteins
Synthesis Fo O-linked glycoside
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
Synthesis of N-linked glycoside
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
How does transport of n linked glycoproteins to lysosomes work?
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
I cell
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
Molecular structure of GAGs
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
