Lecture 23 Flashcards
Collagens are the most _______ protein in the body
Abundant
What are four characteristics of fibrous proteins (collagens and elastin)?
1) Insoluble
2) Stable
3) Long biological half-life
4) High tensile strength and contractibility, respectively
Where do elastins and collagens function?
Elastins and collagens function in extracellular space (matrix)
What are 3 types of collagens?
1) Fibril-forming (classic)
2) Network-forming
3) Fibril-associated
What are characteristics of the structure of collagen?
1) All collagens are triple-helically structured
2) They all have the amino acid structure Gly-X-Y (X is frequently proline; Y is frequently (hydroxy)-proline or (hydroxy)-lysine)
3) They are all rich in (hydroxy)-proline and (hydroxy)-lysine
What modification occurs to the collagen protein post-translationally?
1) Some proline residues are hydroxylated by prolylhydroxylase. Some lysine residues are hydroxylated by lysylhydroxylase
2) Some of these hydroxylated residues are further modified by glycosylation with glucose and galactose
3) Three pro-alpha-chains assemble and form disulfide bonds at the C-terminal propeptide extension. They use a zipper-like folding to form a triple helix
4) Procollagen molecule is secreted from a Golgi vacuole into the extracellular matrix
5) The N-terminal and C-terminal propeptides are cleaved by procollagen peptidases, allowing assembly of collagen into fibrils
Summary:
1) Hydroxylation & Glycosylation
2) Chain association
3) Secretion
4) Cleavage
5) Assembly into fibrils
In order to hydroxylate proline and lysine, what cofactors are required?
Iron 2+ ion and vitamin C
How does collagen structure stabilize its triple helix?
Collagen is cross-linked by lysyl oxidase. Lysyl oxidase requires copper as a cofactor to do so
What are two diseases that affect lysyl oxidase?
1) Menkes Disease
2) Wilson’s Disease
What is Menkes disease?
Menkes disease is an X-linked recessive disorder that is the result of a mutation in the ATP7A gene. Copper is poorly distributed to cells in the body. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels. The lack of copper in certain areas disallows proper structure of collagen due to a lack of function of lysyl oxidase
What is Wilson’s disease?
Wilson’s disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease. The condition is due to mutations in the Wilson disease protein (ATP7B) gene
What is scurvy?
Scurvy is a non-genetically based collagen disorder resulting from a lack of Vitamin C. It results in easily bruised skin, bleeding gums, loosened teeth, “corkscrew hairs”, & poor wound healing. Only common now in places of the world with malnutrition
Who conducted the first clinical trial, what was the disease being tested for, & what was the cure?
Dr. James Lind in 1747; Scurvy; Citrus fruit
What are two genetically-based collagen disorders?
Osteogenesis imperfecta (OI) & Ehlers-Danlos syndrome
Describe the types of Osteogenesis imperfecta (OI)
Type 1 - presents in infancy or early childhood (least severe)
Type 2 - Most severe; usually die in utero or shortly after
2>3>4>1 (in terms of severity)
