Collagen Flashcards
T or F: collagen is an integral membrane protein.
False, it is located completely outside of cells
What sequence is common to all types of collagen?
Gly-X-Y sequence
What type of proteins degrade collagen?
Metalloproteinases
What is primary structural element of connective tissue?
Collagen
T or F: collagen undergoes minimal amounts of post translational processing
False, Collagen is highly post translationally processed
Type I collagen
- Form
- Where
Form:
Fibrillar (fiber form)
Where:
Bone, Skin, Tendon, Cornea, Many others
Type II collagen
- Form
- Where
Form:
Fibrillar
Where:
Cartilage, Vitreous of eye
Type III
- Form
- Where
Form:
Skin, Blood vessels, many other
Type IV
- Form
- Where
Form:
Network
Where:
Basal Lamina Sheets
Type V
- Form
- Where
Form:
Fibrillar
Where:
Bone, Skin, Tendon, Cornea, Many others
***Note: this is the same as type I
Type VIII
- Form
- Where
Form:
Network
Where:
Endothelial Lining, cornea
What features are common to all collagen regardless of tissue type?
- structure
- sequence
- Post-Translational Modifications
Structure:
- 3 domains wound around each other into a triple helix
Sequence:
- Each subunit contains a Gly-X-Y repeating sequence
PTMs:
- Hydroxylation of proline and lysine
T or F: a single collagen fibril contains many collagen strands
True
End to end aggregation of small fibrils form longer fibrils that aggregate to form ____________.
Fibers, collagen fibers self assemble from collagen subunits
T or F: different forms of collagen are genetically distinct
True, many different collagen genes encode for different types
What proteins commonly fill the x, y positions in Gly-X-Y.
- Hydroxyproline (HYP, and PRO)
Why is glycine nesessary at every 3rd amino acid in collagen?
- is H for an R group is the only thing small enough to fit in the triple helix
What is the result of changing gly to cys in the collagen sequence Gly-X-Y?
- Resultant disease
- Cysteine has a larger side chain and puts a bulge in the collagen
- This weakens the collagen
- Osteogenesis imperfecta results (aka brittle bone disease)
**Normally this is a small defect but in collagen this glycine is vital
What it is needed for production of hydroxyproline and hydroxylysine needed for collagen formation?
- what does a deficiency result in?
- Vitamin C
- Vitamin C deficiency leads to scurvy
What enzyme is uses vitamin C as a cofactor?
- Prolyl Hydroxylase enzyme
What are the substrates and products of prolyl hydroxylase?
- Coefactors
Substrates:
Proline + alpha KG + O2
Products:
Hydroxyproline + Succinate + CO2
Cofactor:
VITAMIN C
Lysyl Hydroxylase
- Reaction
- Substrates
- Products
- Coefactors
- make hydroxylysine
Substrate:
Lysine
Product:
Hydroxylysine
Cofactor:
Vitamin C
What addition can be made to hydroxylysine?
***this is important
It can be O-glycosylate for collagen specific glycosylation
Slow wound healing and bleeding of gums and lips are symptoms of what disease related to collagen?
- Scurvy, resulting from Vitamin C deficiency
- Scurvy results from lack of Hyroxyproline and Hydroxylysine
T or F: hydroxyproline and hydroxylysine are essential to collagen formation
True, scruvy is the result of not having these residues
Why would you measure someone’s urine hydroxyproline levels?
- It tells you about bone turnover
***note: hydroxyproline is peed out because it is post-translationally modified and can’t be reused
What would you expect urine hydroxyproline levels to be like in a patient that has scruvy.
Levels will likely be LOW because they lack the appropriate enzymes to make it
Why shouldn’t you eat jellow before a hydroxyproline urine test?
**Don’t eat jello before one of these tests because it contains collagen and will artificially raise your hydroxyproline levels
7 steps of collagen synth.
- Synthesis of Pro-alpha chain
- Hydroxylation of Selected Prolines and lysines
- Glycosylation of selected hydroxylysines
- Self-Assembly of 3 pro-alpha chains
- Procollagen Triple Helix Formation
- Secretion
- Cleavage of Pro-Peptides
Why does lack of hydroxylation causes the effects seen in scurvy?
- Collagen is destabilized and has a lower melting temperature
- Once dissociated the chains are simply degraded
What differentiates Procollagen from collagen?
- what is the importance of this difference?
Procollagen:
- Contains GLOBULAR portions
Purpose of Globular parts:
- help align the 3 strands into a triple helix
T or F: the globular domains must be removed from procollagen to form collagen which can assemble into fibrils and fibers
True
What happens if the globular domains are not removed from the procollagen protein?
Dermatosparaxis:
- Fragile Skin
- Abnormally elastic Skin and Tissues
**Skin loss in cattle and sheep
Why does presence of globular domains on procollagen cause skin to be brittle?
- Collagen needs its ends to be free so that it can bind to other collagens and form large strands
After collagen is assembled what allows for cross linking between strands?
- enzyme
- residues
- Lysyl Oxidase (not hydroxylase) form ALDEHYDES of lysine and hydroxylysine
- Schiff Base is formed
Issues in what 3 areas of collagen formation lead to all of the diseases observed?
- Biosythesis
- Procollagen processing
- Crosslinking
Where does translation of collagen polypeptides typically occur?
RER
What causes Scurvy?
Lack of Vit C, coefactor needed for hydroxylation of proline and lysine
What causes Ehlers-Danlos VI?
- Lysyl Hydroxylase Deficiency
**so you still have your hydroxyprolines
What do you need procollagen domains?
- why is it bad if they are never cleaved?
- Needed for proper alignment
- Must get rid of so that fiber formation can happen
Ehlers-Danlos VII
- Defect
- What part of collagen formation is messed up?
N-propetidase defect
- Globular ends (procollgen domains) are not cleaved
Ehlers-Danlos IX
- Defect
- What part of collagen formation is messed up?
- Lysyl Oxidase deficient
- No Allysine formation so Schiff bases and therefore cross-links can’t be formed
What do lathrogens do?
- effect?
- Inhibit Lysyl Oxidase
- This mimics the effects of Ehlers-Danlos (IX)
Metalloproteinases (MMP)
- Function
- procollagenase
- inhibitor
- Break Down Collagen
Procollagenase:
- activates the MMP
Inhibitor:
TIMPs
What physiologic processes involve metalloproteinases (MMP)?
- Tissue Development
- Cancer Metastasis
- Wound Healing
T or F: globular ends are maintained in Type IV collagen
True, allows it to form a tetramer
**Note: Type IV collagen needed to form a scaffold for the basal lamina
Besides type IV collagen, what other type maintains its globular domain?
Type IX
What is located at the globular end of Type IX collagen?
- what type of collagen is Type IX typically associated with?
a GAG chain
- Type II
What is the relationship between type II and Type IX collagen?
- Type II fiber size is regulated by type IX collagen
ALSO, GAG components of Type IX can interact with other collagens
What forms the sievelike structure of basal laminae?
- Networks Formed by Type IV collagen
What is the job of fibril associated collagens?
- example?
Coat other collagens to:
- Limit Growth of the Fiber
- Enhance interaction of fiber with ECM
What collagen has the job of anchoring fibril to hold epithelia onto underlying CT?
Type VII
