FTM 45 - Proteoglycans and Glycoproteins

Question 1

What is a GAG, proteoglycan, and glycoprotein?

Answer 1

Question 2

Answer 2

Question 3

Describe the basic composition of a GAG.

Answer 3

Question 4

Are GAGs typically more positive or negative? Why?

Answer 4

GAGs have strong negative charges from the carboxyl and sulfate groups.

Question 5

What type of medium do GAGs produce and how? How does the medium help with stuctural integrity?

Answer 5

GAGs produce a gel-like matrix by binding large amounts of water. This matrix is resilient to compression because it just squeezes water out and then reabsorbs it upon relaxation.

Question 6

What are the four primary functions of GAGs?

Answer 6

Question 7

What are the GAGs we need to know?

Answer 7

Chondroitin Sulfate

Keratan Sulfate

Dermatan Sulfate

Heparin

Heparan Sulfate

Question 8

What is the most abundant GAG found in the body and where are they usually found?

Answer 8

Chondroitin Sulfates.

Found in bone, cartilage, ligaments, and the Aorta

Question 9

On what positions can chondroitin be sulfated?

Answer 9

4 or 6

Question 10

Things to know about Keratan Sulfates.

Answer 10

Question 11

Things to know about Dermatain Sulfates

Answer 11

Question 12

Things to know about heparan sulfate

Answer 12

Question 13

Things to know about heparin

Answer 13

Question 14

Why do proteoglycans have a bottle-brush structure? What properties does the structure convey to its medium?

Answer 14

Question 15

List the major steps of proteoglycan synthesis.

Answer 15

Question 16

Where does proteoglycan synthesis occur? Where does their aggregation occur?

Answer 16

They are synthesized intracellularly and they aggregate in the ECM.

Question 17

List the major steps in the synthesis of Glucuronic acid.

Answer 17

Question 18

List the major steps in the synthesis of amino sugars.

Answer 18

Question 19

What serves as the central GAG strand for proteoglycan aggregates? How many of these per central strand on average.

Answer 19

Hyaluronic acid (50,000 units)

Question 20

What are the two primary functions of proteoglycan aggregates?

Answer 20

Shock absorber

Lubricant

Question 21

What makes hyaluronic acid a unique GAG?

Answer 21

Question 22

Where is hyaluronic acid commonly found?

Answer 22

Vitreous humor of the eye

Synovial fluid of the joints

Cartilage

Loose connective tissues

Question 23

What does hyaluronic acid help facilitate?

Answer 23

Cell migration in embryogenesis, morphogenesis, and wound repair

Question 24

Do glycoproteins and proteoglycans contain mainly protein or sugar?

Answer 24

Glycoproteins are mainly protein

Proteoglycans are mainly sugar

Question 25

Things to know about glycoprotein structure.

Answer 25

Question 26

What type of protein are most serum proteins? What is the exception?

Answer 26

Glycoproteins Albumin

Question 27

Things to know about mucins

Answer 27

Question 28

Things to know about blood types and glycoproteins.

Answer 28

Question 29

What are the primary components of the glycocalyx? What are some of its main functions?

Answer 29

Question 30

The components of the glycocalyx have many beneficial functions? What are some of their detrimental functions?

Answer 30

Question 31

How does E. coli adhere to the human body initially?

Answer 31

Question 32

How does H. pylori adhere to the human body initially?

Answer 32

Question 33

What is Dolichol-PP? What is it used for?

Answer 33

A lipid containing many isoprene units (a small hydrocarbon) that is bound to the RER membrane. This compound is used to hold a mannose rich oligosaccharide that will later be transferred to an aspargine residue of a protein.

Question 34

Which proteins will be N-glycosylated?

Answer 34

All proteins that are synthesized by the RER will be N-glycosylated by a mannose rich precursor. This precursor will be modified later

Question 35

After a protein has been N-glycosylated, what happens to it?

Answer 35

The mannose-rich oligosaccharide begins to carbohydrates trimmed off while still in the RER lumen. This trimming continues in the golgi resulting in the protein becoming a high-mannose glycoprotein or a complex glycoprotein.

Question 36

How does a protein get sent to a lysosome?

Answer 36

During post-translational modification a _specific phosphotransferase_ which can recognize lysosomal proteins begins the process of N-glycosylating these proteins with mannose 6-P. A mannose 6-P receptor in the golgi will bind to the lysosomal enzyme and package them into vesicles for transport into lysosomes where they will be activated.

Question 37

What lysosomal storage disease do we need to know? What causes it and what are its symptoms?

Answer 37

I-cell disease Caused by a deficiency of the phosphotransferase needed to N-glycosylate a lysosomal protein with M6P. This leads to the lysosomal protein being secreted by the cell instead of being sent to the lysosome. Consequently, lysosomes cannot degrade waste molecules and they accumulate, forming inclusion bodies (I-cell).

Question 38

Which amino acids undergo O-glycosylation and which ones undergo N-glycosylation?

Answer 38

O-glycosylation - serine, threonine, hydroxylysine N-glycosylation - asparagine and glutamine

Question 39

What is a key differnce between O and N-glycosylation besides where the sugar is linked?

Answer 39

O-glycosylation involves _individual linkage_ of sugars _step by step_ directly to the protein while N-glycosylation involves the transfer of an oligosaccharide from Dolichol-PP to the protein