Connective Tissue And Components Flashcards
what are the structural function of ECM?
maintains the three-dimensional structure of the body, forms the sheet of the basement membrane (basal lamina), and holds cells and tissues together
What are the regulatory functions of the ECM?
Regulates processes like proliferation, differentiation, migration, and cell-cell recognition. It can prevent of limit the movement of cancer cells and microorganisms…
Matrix Metallo-proteinases
MMP-group of enzymes that constantly remodel the ECM, includes the collagenases
What does the dysregulation of MMPs lead to?
The spread of cancer-due to the fact that the ECM can limit cancer cells from moving, so if it’s not being maintained then the cells could move
What are the insoluble proteins of the extracellular matrix?
Collagen and elastin
Collagen
Most abundant fibrous protein (25-30% of total body protein mass).
What is the structure of a typical collagen molecule?
A triple helix of three alpha chains which are tightly wound around each other and form a rope like structure
Glycine in Collagen
Glycine is found in each third position of the alpha chain, which allows a tight-winding of the triple helix.
Proline in Collagen
Abundant and lead to “kinks” (due to their ring structure) in the protein chain that allow for tight winding
Hydroxyproline and Collagen
Hydroxyproline residues stabilize the triple helix via MANY hydrogen bonds between the alpha chains
Lysine and collagen
Form covalent bonds and cross-link tropocollagen
Hydroxylysine
Hydroxylysine residues allow for the additions of sugars
What are the 3 general types of collagen fibers?
Fibril forming, network forming, and fibril associated.
Collagen Type 1
Most common type. Fibril Forming. Makes up the skin, bone, tendon, blood vessels, and cornea
Collagen Type2
Cartilage, intervertebral disk, and vitreous body. Fibril forming.
Collagen Type III
Fibril forming. Makes up blood vessels and fetal skin
Collagen Type IV
Network forming. Makes up the basement membrane.
Collagen Type VII
Network Forming. Found beneath stratified squamous epithelia.
Collagen Type IX
Fibril Associated. Found in cartilage
Collagen Type XII
Fibril Associated. Found in tissue, ligaments, and some other issues.
Collagen in the bones
Arranged to resist mechanical shear
Collagen in tendons
Bundles in tight, parallel fibers and provides great strength
Collagen Biosynthesis
Collagen is created at the level of a soluble procollagen (still has pro-peptides)
The 3 pro-alpha-chains are modified by specific hydroxylation or glycosylation and a triple helix is formed.
Molecule is released into the ECM and the propeptides are cleaved forming an insoluble collagen.
Collagen molecules associate to form a collagen fibril.
Extracellular cross linking with lysine or modified lysine results in mature collagen fibers.
Where is procollagen synthesized?
Fibroblasts, osteoblasts, and chondroblasts
What do COL1A1 and COL1A2 lead to?
Two a1 chains and one a2 chain for the triple helix.
What is the cofactor for prolyl hydroxylase and lysyl hydroxylase?
Vitamin C (ascorbic acid)
Hydroxyproline
A hydroxylated proline molecule that allows hydrogen bonds between the three alpha chains (stabilizes the triple helix)
Hydroxylysine
Hydroxylated lysine that can be further glycosylated by glucose or galactose
What are the three functions of propeptides?
1) needed in cytosol for the linkage of the correct three pro-alpha-chains to each other by disulfide bonds
2) Allow efficient winding during triple helix formation
3) Keep the procollagen soluble
Procollagen Peptidases
Enzymes that cleave the propeptides from the procollagen.
Tropocollagen
Collagen after the propeptides have been cleaved. Tropocollagen molecules spontaneously associate to form a collagen fibril (each overlaps its neighbor) leading to a striated appearance.
What does scurvy cause?
Decreased stability and tensile strength of collagen, which leads to bleeding gums, hemorrhages, and poor wound healing.
Is is extracellular cross-linking performed?
The EC enzyme lysyl oxidase (require copper) oxidatively deaminates lysine residues in collagen. This results in a free ammonia and an aldehyde residue known as allysine (or hydroxyallysine). The reactive aldehyde forms a covalent bond with other lysine or modified lysine residues.
What happens if there is a copper deficiency?
reduced collagen cross-linking
What can cause Ehlers-Danlos Syndrome?
Connective tissue disorder. Can result from a mutation of a gene for the pro-alpha chains of collagen or result from a hereditary defect related to one of the enzymes that are needed for correct collagen synthesis/
What types of collagen are usually affected by Ehlers-Danlos Syndrome?
Type I, III, and V
What are the symptoms of classic (Type V) Ehlers-Danlos syndrome?
Hypermobility of joints and hyperextensibility of the skin
Vascular Ehlers-Danlos Sndrome
Caused by defects of type III collagen and leads to fragility of skin and vascular walls. It is most serious as arteries can rupture.