MSKS BioChem Lecture 1_CT ECM

Question 1

What causes Williams-(Beuren) Syndrome?

Answer 1

Cause - chromosomal (#7) deletion of ~27 genes including elastin. This condition is typically a result of new mutations.

Question 2

Describe Marfan syndrome

Answer 2

Marfan syndrome is an autosomal dominant Pleiotropic mutation that effects the formation of fibrillin 1. This alters the structure of elastic fibers (becasue fibrillin provides the scafold for elastin in the formation of elastic fibers)

Question 3

Proteoglycans vs Glycoproteins

Answer 3

Proteoglycans are polysacrides with a little protein. Glycoproteins are proteins with a little carbohydrate.

Question 4

What are the properties of Karatin Sulphates?

Answer 4

See attached

Question 5

Describe the structure of collegen

Answer 5

Collegen is composed of three alpha chains that hydrogen bond together to from a collegen rope. Each alpha chain is ~1000 AA long. About 1/3 of the AAs are Gly and 20% proline (often get hydroxylated to form hydroxyproline)

Question 6

Describe the structure of elastic fibers

Answer 6

Elastic fibers are composed of amorphus elastin that is formed around a fibrillin scafold (fibrillin is a large family of glycoproteins)

Question 7

What are the properties of dermatan sulfate

Answer 7

see attached

Question 8

What are the general features of Ehlers-Danlos Syndrome (EDS)

Answer 8

General features: hyperextensible skin,
hypermobile joints and abnormal tissue
fragility (easy bleeding/bruising) which all result from Defective collagens

Question 9

What is the structure of GAGs?

Answer 9

See attached

Question 10

What are the 3 main types of collegen? What are the sub types and what do they form?

Answer 10

See attached

Question 11

What is the pathology of vitamin C deficiency (Scurvy)

Answer 11

The proline in the collegen alpha chain is often hydroxylated into hydroxyproline. This hydroxylation allows for increased hydrogen bonding between the three alpha chains. The proline is hydroxylated in the ER by the enzyme Prolyl Hydroxylase. Prolyl Hydroxylase requires Ascorbate (vitamin C) and Fe++ to function. A vit C deficiency prevents hydroxylation which results in collegen that has a reduced tensile strength. This manifests as:

‣Easy bruising
‣Loose teeth and bleeding gums
‣Poor wound healing
‣Poor bone development

Question 12

What are the properties of Hyaluronic Acid?

Answer 12

see attached

Question 13

What are the properties of chondroitin sulphates

Answer 13

See attached

Question 14

Describe Laminin

Answer 14

It is a heterotrimers extracellular protein that is responsible for holding together the components of the basement membrane. It binds to integrin on the cell surface and then to collegen and other components of the ECM. Mutations in LAMA2 gene can lead to muscular dystrophy

Question 15

What causes Menkes syndrome?

Answer 15

mutations in the ATP7A gene leads to lack of Cu2+. This makes lysyl oxidase less active and thus prevents crosslinking of collegen fibers. Menkes is an x linked condition but 30% of cases are a result of denovo mutations. The symptomes include:

Symptoms: weak muscle tone (hypotonia), sagging
facial features, seizures, intellectual disability, and
developmental delay. The patients have brittle hair
(kinky hair disease)

Question 16

Describe collegen crosslinking.

Answer 16

*They reffers to the reactive aldhydes

Question 17

What are the properties of heparin sulfate

Answer 17

see attached

Question 18

What are the properties of Heparin

Answer 18

see attached

Question 19

What is the role of Fibronectin?

Answer 19

Similar to the function of laminin

Question 20

What are the three components of the ECM?

Answer 20

1) Fibers (elastic, collegen, etc) 2) Grounding substance ( Proteoglycan, GAG) 3) Cells (generically refered to as fibroblasts)

Question 21

What typically causes ostiogenesis imperfecta?

Answer 21

Is typically a mutation that replaces the glysines with a different amino acid. This disrupts the alpha chain structure and leads to weaker hydrogen bonding.