Proteoglycans/Glycoproteins/Glycolipids

Question 1

General properties of proteoglycans

Answer 1

Modest amount of protein and abundant neg charged polysaccs w/disacc repeats. Large vol role = large amount of carbs creates water absorbing = lube, shock absorb, and space fill. Major metabolic destination for glucose

Question 2

GAGs (proteoglycan) struc

Answer 2

Protein core with lots of sugar chains. Assembled in golgi. Hold CT together and btwn joints

Question 3

Glycoproteins structure

Answer 3

protein and sugar accessory, target signaling, applied at ER. Protein > sugar

Question 4

Determination of charge

Answer 4

Number of sulfur bonds determine neg charge strength

Question 5

Chondroitin 4/6 - sulfate

Answer 5

Disacc = GalNAc and GlcUA, most abundant, located in cartilage, tendons, ligaments, aorta. Binds collagen

Question 6

Keraten sulfates 1 and 2

Answer 6

Disacc - Gal and GlcNAc. In loose CT and cornea

Question 7

Dermatin Sulfate

Answer 7

Disacc = IdUA and Gal NAc. In skin, bv’s and heart valves

Question 8

Heparin/ Hep Sulfate

Answer 8

Disacc = GlcUA and GlcN. alpha linkage (rest beta), helps sequester Ca.

Heparin - IC = mast cells = anticoag
Hep Sulf - EC = Basement membrane and cell surface

Question 9

Hyaluronic Acid

Answer 9

No S group, not covalently attached to protein. Disacc = GlcUA and GlcNAC. Lube and shock absorb

Question 10

GAGs and protein core

Answer 10

Except Hyaluronic acid, all covalently bound to Serine (Thr is N-linked, AA residue = Asp)

Question 11

Proteoglycan synth

Answer 11

neg charges make it look like a bottle brush

1. Protein component on RER
2. Enters ER lumen - intial glycosylation
3. UDP sugars donate Carb units 1 by 1 always at nonreducing end of growing chain
4. To golgi
5. glycosyl transferase (specific to sugar added)
6. After primary sugars added, alt actions of 2 glycosyl transferases adds repeating sequences
7. Sulfation after sugar added, source = PAPs (phosphoadenosyl phosphosulfate)
8. Source of iduronate - epimerization of glucouronate
9. After synth - secreted from cell

Question 12

Sulfation of carb chains

Answer 12

After sugar attached to nascent carb chain, sulfotransferase attach SO4 from PAPs. Synth of PAPs (cost 3 ATP) via attach to ATP. Defect in sulfation leads to chondrodystrophy = less skl dev

Question 13

Synth of NANA

Answer 13

At terminus of chain, at each step UDP sugar present
To create 9C NANA, PEPs 3C body is required and inserted into hexose structure (fructose is source of acetyl glucosamine).
Hydrolysis of Phos = free NANA/ Sialic acid (from PEP step)

Question 14

Glucose to GAG synth

Answer 14

Around 20% enter golgi and ER lumen of liver. F6P is precursor of GlcNAc, GlNAc, NANA (recognition element)

NANA is sole sugar derivative activated by CMP (others need dinucleotide activation)

Question 15

Degradation of GAGs

Answer 15

Lysosomes via hydrolysis (M6P tag) and Glycosidases - remove sugar. Phagocytosis proceeds degradation. Glyco (endo = creates short oligos) (exo = specific to linkage and reduce sugars singlely from nonreducing end)

Question 16

Mucopolysaccharidosis

Answer 16

GAG degrade disorders, all but Hunters are AR. Accumulation prevents call and tissue remodeling. Defect in exo-glycosidases

Question 17

Hurlers Syndrome

Answer 17

Defect in alpha-L-iduronidase leading to coarse features, dwarf, corneal clouding. Accumulation of Hep sulfate and Dermatin Sulfate

Question 18

Hunters Syndrome

Answer 18

Def in Iduronate sulfatase. X-linked, no corneal clouding. accum of Hep sulfate and dermatin sulfate

Question 19

Sanflippos

Answer 19

Defect in removal of sulfated or acetylated glucosamines. severe CNS def and retardation. Acuum of hep sulfate

Question 20

Sly Syndrome

Answer 20

Def in beta-glucoramidase. Hepatosplenemegaly, corneal clouding, skl deform. Accum of Dermatin and Hep Sulfate

Question 21

Glycoproteins

Answer 21

Carb chains short and branched. No specific charge. Increased variability in function. Secreted globular proteins

Question 22

Glycoprotein Structure

Answer 22

Oligos are D-hexoses with NANA
N-linked (Asp link) - branched glycoprotein and have increased mannose content
O-linked (Ser/Thr) - abundant H bonds and NANA neg charge

Question 23

Synth of glycoproteins

Answer 23

1. Precursors are sugar nucleotides (also serine as recog molecule)
2. All attachments convalent and strongly exergonic
3. O link: Ser/Thr with single sugars added. N-link - Dolichol PP acquires oligo and transfers branched Carb to protein
4. Trimming and additions as GP passes through golgi: sorting and labeling at terminus via fructose or NANA

Question 24

I cell disease

Answer 24

M6P missing, def in golgi phosphotransferase leading to inclusion bodies

Question 25

Glycolipids

Answer 25

Derivatives of 18C aminoalchohol sphingosine
Connection to FA via ceramide bond = stable amide. Ceramide strong and long lipid structure permits stable Hydrophobic lodging in cell

Question 26

ABO

Answer 26

General structure is X-(Fruc)-GlcNAc-R
Distinct Ag termini only on A and B, O has no gal base.
R = protein or ceramide lodged in membrane

Question 27

Synth of glycolipids

Answer 27

Synth platform = Ceramide in golgi - resembles GP process
Cerebrosides = ceramide and single glucose or gal
Gangliosides = ceramide and oligosacc

Question 28

Defects in degrade of glycolipids

Answer 28

Cause sphingolipidoses, ceramide product accum

Question 29

Tay Sachs

Answer 29

def in Hexosaminidase A

Question 30

Fabry

Answer 30

def in alpha-galactosidase

Question 31

Niemann Pick

Answer 31

def in sphingomyelinase