3 cellular Collagen Collagen synthesis and structure Osteogenesis imperfecta Ehlers-Danlos Menkes Disease Elastin

Question 1

What is the most abundant protein in the human body and what is its function?

Answer 1

Collagen; it strengthens and organizes the extracellular matrix

Question 2

What type of collagen is found in the basement membrane, basal lamina, and lens?

Answer 2

Type IV (under the floor [IV])

Question 3

What type of collagen is found in the vitreous body, nucleus pulposus, hyaline cartilage, and articular surface of joints?

Answer 3

Type II (cartwolage [cartilage])

Question 4

What is another name for type III collagen? In what structures can type III collagen be found?

Answer 4

Reticulin; found in skin, blood vessels, uterus, granulation tissue, and fetal tissue

Question 5

What is the most common type of collagen? In what structures can this type of collagen be found?

Answer 5

Type I collagen (90%); found in bone, skin, dentin, tendon, fascia, and cornea; also involved in late wound repair

Question 6

A baby is born with multiple fractures, loose joints, and blue sclerae. What type of collagen is defective?

Answer 6

Insufficient production of type I collagen (disease is osteogenesis imperfecta type I)

Question 7

A 13-year-old boy presents with hearing loss, hematuria, and end-stage kidney disease. What type of collagen is most likely defective?

Answer 7

Type IV—disease is Alport syndrome

Question 8

A patient has autoantibodies attacking his glomerular basement membranes. What type of collagen is most likely being targeted?

Answer 8

Type IV collagen—disease is Goodpasture syndrome

Question 9

Which type of collagen is deficient in the vascular type of Ehlers-Danlos syndrome?

Answer 9

Type III collagen (type III, which is deficient in the uncommon vascular type of Ehlers-Danlos syndrome [ThreE D])

Question 10

A man takes a drug that interferes with posttranslational modification. Will this affect his bone, skin, and tendon production?

Answer 10

Yes, because collagen (including type I, which is found in bone, skin, and tendon) undergoes extensive posttranslational modification

Question 11

What form of collagen is exocytosed from the cell into the extracellular space?

Answer 11

Procollagen

Question 12

What form of collagen is exocytosed from the cell into the extracellular space?

Answer 12

Procollagen

Question 13

The conversion of preprocollagen to procollagen requires what process?

Answer 13

Glycosylation

Question 14

A single-collagen α chain during collagen synthesis is referred to as what?

Answer 14

Preprocollagen

Question 15

Many staggered tropocollagen molecules with covalent lysine-hydroxylysine cross-links are referred to as ____.

Answer 15

Collagen fibrils

Question 16

Where does collagen synthesis mainly occur in the cell?

Answer 16

In the rough endoplasmic reticulum

Question 17

Is tropocollagen formed inside or outside fibroblasts?

Answer 17

Outside

Question 18

British sailors present with an inability to hydroxylate proline and lysine residues. Why do you prescribe them limes?

Answer 18

They have scurvy, and limes supply the vitamin C that they need (and earn them the nickname “limeys”)

Question 19

Which vitamin is required for the hydroxylation of proline and lysine residues in collagen?

Answer 19

Vitamin C

Question 20

A triple helix that is composed of three collagen α chains with the terminal disulfide-rich regions cleaved off is referred to as what?

Answer 20

Tropocollagen

Question 21

Which enzyme covalently cross-links lysine residues to hydroxylysine residues to make collagen fibrils? Which disease does a defect cause?

Answer 21

Lysyl oxidase (containing copper); Menkes disease

Question 22

• _____ (Proline/Glycine/Lysine) content best reflects collagen synthesis.

Answer 22

Glycine, as collagen is one third glycine

Question 23

A man presents with easy bruising and ecchymoses. You find that he has defective cross-linking of tropocollagen. What disease does he have?

Answer 23

Ehlers-Danlos syndrome

Question 24

What type of inheritance does the most common variant of osteogenesis imperfecta show?

Answer 24

Autosomal dominant

Question 25

Of what process is osteogenesis imperfecta a defect?

Answer 25

Production of type I collagen—production of otherwise normal type I collagen is insufficient

Question 26

The dental imperfections seen in osteogenesis imperfecta are due to lack of ____ in the teeth.

Answer 26

Dentin

Question 27

A young woman with blue sclerae also has hearing loss. What is the pathophysiology of her hearing loss?

Answer 27

Abnormal ossicles (this is osteogenesis imperfecta)

Question 28

Like polycystic kidney disease, Ehlers-Danlos syndrome is associated with what defects of the brain vasculature?

Answer 28

Berry aneurysms (also associated with aortic aneurysms)

Question 29

Ehlers-Danlos syndrome is transmitted through what inheritance pattern(s)?

Answer 29

Can be either autosomal dominant or recessive

Question 30

A patient presents with hyperextensible skin, easy bruising, and hypermobile joints. What is the most likely mutation?

Answer 30

A mutation in type V collagen, resulting in Ehlers-Danlos syndrome, classical type (joint and skin symptoms)

Question 31

Autopsy of a 50 year old with recurrent joint dislocations reveals death from splenic rupture. What is the mechanism of action of his death?

Answer 31

Poor type III collagen synthesis resulting in weak connective tissue is the vascular type Ehlers-Danlos syndrome

Question 32

A patient presents with brittle, "kinky" hair, growth retardation, and hypotonia. What gene mutation is responsible?

Answer 32

This is Menkes disease, caused by a defect in Menkes protein (ATP7A)

Question 33

Impaired copper absorption and transport could result in which connective tissue disease?

Answer 33

Menkes disease

Question 34

Why is copper a critical factor in the development of Menkes disease?

Answer 34

Copper is a required cofactor for lysyl oxidase, an enzyme that makes collagen fibrils from tropocollagen

Question 35

What enzyme is inhibited by α1-antitrypsin?

Answer 35

α1-antitrypsin inhibits elastase, which degrades elastin

Question 36

A man presents with long, slender limbs as well as long fingers and toes. You found that he has defective fibrillin. What is your diagnosis?

Answer 36

Marfan syndrome

Question 37

What is the function of fibrillin?

Answer 37

It acts as a scaffold for tropoelastin

Question 38

A man with no smoking history presents with emphysema. He was also found to have excess elastase activity. What deficiency might he have?

Answer 38

α1-antitrypsin deficiency

Question 39

Name six locations in the body where elastin may be found.

Answer 39

Lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect vertebrae with relaxed and stretched conformations), skin

Question 40

A patient is distraught about her aging and wants to know why her skin is becoming more wrinkled. What is a good explanation to give her?

Answer 40

As she ages, she has decreased collagen and elastin production, which leads to wrinkle formation