3 cellular Collagen Collagen synthesis and structure Osteogenesis imperfecta Ehlers-Danlos Menkes Disease Elastin Flashcards
What is the most abundant protein in the human body and what is its function?
Collagen; it strengthens and organizes the extracellular matrix
What type of collagen is found in the basement membrane, basal lamina, and lens?
Type IV (under the floor [IV])
What type of collagen is found in the vitreous body, nucleus pulposus, hyaline cartilage, and articular surface of joints?
Type II (cartwolage [cartilage])
What is another name for type III collagen? In what structures can type III collagen be found?
Reticulin; found in skin, blood vessels, uterus, granulation tissue, and fetal tissue
What is the most common type of collagen? In what structures can this type of collagen be found?
Type I collagen (90%); found in bone, skin, dentin, tendon, fascia, and cornea; also involved in late wound repair
A baby is born with multiple fractures, loose joints, and blue sclerae. What type of collagen is defective?
Insufficient production of type I collagen (disease is osteogenesis imperfecta type I)
A 13-year-old boy presents with hearing loss, hematuria, and end-stage kidney disease. What type of collagen is most likely defective?
Type IV—disease is Alport syndrome
A patient has autoantibodies attacking his glomerular basement membranes. What type of collagen is most likely being targeted?
Type IV collagen—disease is Goodpasture syndrome
Which type of collagen is deficient in the vascular type of Ehlers-Danlos syndrome?
Type III collagen (type III, which is deficient in the uncommon vascular type of Ehlers-Danlos syndrome [ThreE D])
A man takes a drug that interferes with posttranslational modification. Will this affect his bone, skin, and tendon production?
Yes, because collagen (including type I, which is found in bone, skin, and tendon) undergoes extensive posttranslational modification
What form of collagen is exocytosed from the cell into the extracellular space?
Procollagen
What form of collagen is exocytosed from the cell into the extracellular space?
Procollagen
The conversion of preprocollagen to procollagen requires what process?
Glycosylation
A single-collagen α chain during collagen synthesis is referred to as what?
Preprocollagen
Many staggered tropocollagen molecules with covalent lysine-hydroxylysine cross-links are referred to as ____.
Collagen fibrils
Where does collagen synthesis mainly occur in the cell?
In the rough endoplasmic reticulum
Is tropocollagen formed inside or outside fibroblasts?
Outside
British sailors present with an inability to hydroxylate proline and lysine residues. Why do you prescribe them limes?
They have scurvy, and limes supply the vitamin C that they need (and earn them the nickname “limeys”)
Which vitamin is required for the hydroxylation of proline and lysine residues in collagen?
Vitamin C
A triple helix that is composed of three collagen α chains with the terminal disulfide-rich regions cleaved off is referred to as what?
Tropocollagen
Which enzyme covalently cross-links lysine residues to hydroxylysine residues to make collagen fibrils? Which disease does a defect cause?
Lysyl oxidase (containing copper); Menkes disease
• _____ (Proline/Glycine/Lysine) content best reflects collagen synthesis.
Glycine, as collagen is one third glycine
A man presents with easy bruising and ecchymoses. You find that he has defective cross-linking of tropocollagen. What disease does he have?
Ehlers-Danlos syndrome
What type of inheritance does the most common variant of osteogenesis imperfecta show?
Autosomal dominant
Of what process is osteogenesis imperfecta a defect?
Production of type I collagen—production of otherwise normal type I collagen is insufficient
The dental imperfections seen in osteogenesis imperfecta are due to lack of ____ in the teeth.
Dentin
A young woman with blue sclerae also has hearing loss. What is the pathophysiology of her hearing loss?
Abnormal ossicles (this is osteogenesis imperfecta)
Like polycystic kidney disease, Ehlers-Danlos syndrome is associated with what defects of the brain vasculature?
Berry aneurysms (also associated with aortic aneurysms)
Ehlers-Danlos syndrome is transmitted through what inheritance pattern(s)?
Can be either autosomal dominant or recessive
A patient presents with hyperextensible skin, easy bruising, and hypermobile joints. What is the most likely mutation?
A mutation in type V collagen, resulting in Ehlers-Danlos syndrome, classical type (joint and skin symptoms)
Autopsy of a 50 year old with recurrent joint dislocations reveals death from splenic rupture. What is the mechanism of action of his death?
Poor type III collagen synthesis resulting in weak connective tissue is the vascular type Ehlers-Danlos syndrome
A patient presents with brittle, “kinky” hair, growth retardation, and hypotonia. What gene mutation is responsible?
This is Menkes disease, caused by a defect in Menkes protein (ATP7A)
Impaired copper absorption and transport could result in which connective tissue disease?
Menkes disease
Why is copper a critical factor in the development of Menkes disease?
Copper is a required cofactor for lysyl oxidase, an enzyme that makes collagen fibrils from tropocollagen
What enzyme is inhibited by α1-antitrypsin?
α1-antitrypsin inhibits elastase, which degrades elastin
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?
Marfan syndrome
What is the function of fibrillin?
It acts as a scaffold for tropoelastin
A man with no smoking history presents with emphysema. He was also found to have excess elastase activity. What deficiency might he have?
α1-antitrypsin deficiency
Name six locations in the body where elastin may be found.
Lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect vertebrae with relaxed and stretched conformations), skin
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?
As she ages, she has decreased collagen and elastin production, which leads to wrinkle formation
