2.6.1. Part 2 of 2 Collagen and Proteoglycan (Proteoglycan Only)

Question 1

Function of proteoglycans?

Answer 1

Mechanical resiliency

Question 2

What provides for the mechanical resiliency?

Answer 2

Unique structure of the carbohydrates

Question 3

What does proteoglycan fuse with and what does this give us?

Answer 3

When combined with collagen, forms “composite material” properties of the ECM

Question 4

Structure of proteoglycan

Answer 4

Uronic acid + “-osamine” [amino sugar]

Question 5

What structure determines the properties of proteoglycan?

Answer 5

Properties vary based on the type and amount of glycosaminoglycans present

Question 6

What major monosaccharide units make up hyaluronate?

Answer 6

Glucoronic acid

N-Acetyl glucosamine

Question 7

What major monosaccharide units make up Dermatan sulfate?

Answer 7

L-iduronate

N-Acetyl galactosamine 4-sulfate

Question 8

What major monosaccharide units make up Chondroitin 6-sulfate?

Answer 8

Glucoronic acid

N-Acetyl galactosamine 6-sulfate

Question 9

What major monosaccharide units make up Keratan sulfate?

Answer 9

Galactose

N-Acetyl glucosamine 6-sulfate

Question 10

What major monosaccharide units make up Heparin

Answer 10

L-iduronate 2 sulfate

Glucosamine 6-sulfate

Question 11

What are the 5 types of monosaccharides found in GAGs?

Answer 11

N-Acetyl glucosamine
N-Acetyl-galactosamine
Glucuronic acid
Iduronic acid
Galactose

Question 12

What is the first step of proteoglycan synthesis?

Answer 12

Sugars are added to a protein, one at a time, with UDP sugars serving as the precursors.

Question 13

What happens in proteoglycan synthesis after this step:

Sugars are added to a protein, one at a time, with UDP sugars serving as the precursors.

Answer 13

Two galactose residues are added, followed by a glucuronic acid and an N-acetylglucosamine

Question 14

What happens in proteoglycan synthesis after these steps:

Sugars are added to a protein, one at a time, with UDP sugars serving as the precursors.

Two galactose residues are added, followed by a glucuronic acid and an N-acetylglucosamine

Answer 14

Subsequent additions occur by the alternating action of two enzymes that produce the repeating disaccharide units.

One adds GlcUA
One adds CalNAc

Question 15

In proteoglycan synthesis, as the chain starts to grow, what groups are added and by what?

Answer 15

As the chain grows, sulfide groups are added by phosphoadenosine phosphosulfate (PAPS)

Also known as “active sulfate”

Question 16

Hunter syndrome is caused by a deficiency in what?

Answer 16

iduronate sulfatase

Question 17

Hurler Syndromeis caused by a deficiency in what?

Answer 17

L-iuronidase

Question 18

Maroteaux-Lamy Syndrome is caused by a deficiency in what?

Answer 18

N-acetylgalactosamine sulfatase

Question 19

Sandhoff disease is caused by a deficiency in what?

Answer 19

B-hexosaminidase A and B

Question 20

Sly syndrome (MPS VII) is caused by a deficiency in what?

Answer 20

B-glucuronidase

Question 21

What are characteristics, etiology, cause, and diagnosis method for Hurler syndrome?

Answer 21

Deficiency of a-L-iuronidase

Osmotically active polymers accumulate in many tissues

Diagnosis at 6-24; need to demonstrate enzyme deficiency in cultured fibroblasts from the patient

Characterized by developmental delays, mental retardation, coarse facial features with macroglossia, skeletal abnormalities and mental retardation

Palliative treatment

Question 22

What is hyaluronic acid?

Answer 22

a glycosaminoglycan found in synovial fluid and cartilage

Question 23

Hunters vs. Hurlers genetic pattern

Answer 23

Hunters: X-linked; Hurlers: autosomal recessive; MPSI resulting from the buildup of glycosaminoglycans

Question 24

Mucopolysaccaridoses?

Answer 24

• generic name for diseases resulting from the accumulation of mucopolysaccharides

Question 25

Glycosaminoglycan?

Answer 25

various disaccharide repeating units and usually occuring in proteoglycans

Question 26

Order of the enzymes used to degrade proteoglycans

Answer 26

1. Iduronate sulfatase
2. a-L-iduronidase
3. N-acetylgalactosamine-sulfatase
4. B - Hexosaminidase A and B
5. B - glucuronidase