Biochemistry Of connective Tissue ECM Flashcards
Fibrin-forming types of collagen
Type 1-3
Type 1 collagen
Forms fibrils in skin,bone,tendon, blood vessels and cornea
- made up of 2 (a1) and 1 (a2) chains
Type 2 collagen
Fibrin-forming in cartilage, intervertebral disks, vitreous bodies
-made up of 3 (a1) chains
Type 3 collagen
Forms fibrils in blood vessels, skin and muscle
Network-forming types of collagen
Types 4 and 8
Type 4 collagen
Network-forming collagen found in basement membrane
Type 8 collagen
Network-forming collagen found in corneal and vascular endothelium
Fibril-associated collagen types
Types 9 and 12
Type 9 collagen
Fibril-associated collagen found in cartilage
Collagen type 12
Fibril-associated collagen found in tendons and Ligaments
Collagen basic structure
Fibrous protein shaped in via 3-(a) chains. Stabilized by intrachained H-bonds.
- each (a)-chain is encoded by a different gene
- Rich in Gly and Pro amino acids.
- every 3rd amino acid is a “Gly”
Hydroxylated amino acids found in collagen
HydroxyPROLINE
hydroxyLYSINE
- requires, oxygen, iron and vitamin C (ascorbate) to hydroxylate amino acids*
- occurs in rough ER
Cross linking of collagen
Cooper-containing extracellular enzymes delaminates lysine and hydroxylysine residues to reactive aldehyde groups.
These aldehyde groups can cross link with each other in mature collagen fibers, further promoting tension strength.
Collagen synthesis occurs where?
Endoplasmic reticulum = procollagen (immature) formation
Extracellular matrix = mature collagen
Steps of transforming procollagen into collagen in the extracellular matrix
N and C proteinases cleave propeptides
- collagen fibrils are formed
- Lysyl oxidase begins formation of aldehyde groups that covalently crosslink with each other.
Collagenopathies
Genetic diseases due to defects in one of the steps of collagen fiber synthesis
Elastic fiber composition
Inner core of elastin protein surrounded by microfibils of fibrilin
- very interconnected via cross linking, allowing it to “bounce back” to its original structure.
- lysyl oxidase is the enzyme that does the cross-linking.
Fibrillins
Glycoproteins that provide scaffold for elastin
major group is Fibrillin-1
Laminin
Large cross shaped glycoproteins that consists of 3 polypeptide chains encoded by different genes (heterotrimer)
Functions to hold components of the basement membrane together, trigger physiological responses, growth and movement of the body.
Quarternary protein
Fibronectin
large protein formed by two polypeptide chains linked by disulfide bonds. Binds to heparan sulfate proteoglycans.
Functions to glue cells to fibrous matrix in ECM, movement of cells In embryogenesis and metastasis of cancer
Most abundant multi-adhesive protein
Proteoglycans vs Glycoproteins
Proteoglycans: high carb, low protein percentages
(95% carbs: 5% proteins)
Heteropolysaccharide chains
Glycoproteins: high protein, low carb percentages
Proteoglycans functions
Gel-like matrix that provides flexible support in ECM and lubricating properties.
Influences movement of material through ECM
Lubricating properties of mucus
Glycosaminoglycans (GAGs)
Large complexes of negatively charged heteropolysaccharide chains.
Formed by a repeating disaccharide unit of an acidic sugar and an N-acetylated amino sugar.
Attracts water via the N-acetylated sugar
6 major classes Sorted by composition, type of glycosidic linkage and degree/location of sulfate units.
How is collagen synthesized
Synthesized in the cells of CT in their endoplasmic reticulum.
Ribosomes synthesize the individual chains of collagen fibers.
Move to the lumen of the ER and hydroxylation and glycosylation of the proline/lysine residues
Forms the procollagen
Moves to extracellular matrix via transport vesicles Where the terminals of procollagen are cleaved
Lysyl oxidase then binds procollagen fibers together to generate mature collagen
Structures in proteoglycans aggregates
GAGs
A core protein
Hyaluronic acid
A link protein
Chondroitin 4-6 sulfate
Class of GAG
Most abundant GAG in the body that is found in cartilage, tendons ligaments and aorta.
From aggregates via noncovalent bonds with hyaluronic acid
Keratan sulfates
Class of GAG
Most heterogenous GAG containing additional monosaccharides
Found in cornea (subtype 1) and loose connective tissue (subtype 2).
Aggregates with non-covalent bonding with chondroitin sulfate
Hyaluronic acid
Class of GAG
NOT sulfates and not covalently bound to any protein.
Found in bacteria as well as animal tissue
Serves as lubricant and shock absorber
Found in synovial fluid of joints, vitreous humor of the eye, loose CT and cartilage.
Dermatan sulfate
Class of GAG
Found in skin, blood vessels and heart valves
Heparin
Class of GAG
(A)-sulfur linkages joins disaccharides, only one to do so
ONLY INTRACELLULAR GAG, in Mast cells exclusively
Serves as an anticoagulant
Heparan sulfate
Class of GAG
Found in basement membrane and as a ubiquitous component of cell surfaces.
Metabolism of GAGs
Synthesized in this order
- core protein
- carb chains
- sulfonation post-modification in carb chains
Degradation:
By endocytosis and Lysosomes
Chondrosytrophies
Defects in the sulfonation of GAGs (affects synthesis)
Autosomal recessive
Causes dwarfism
Mucopolysaccharidoses
Deficiency of lysosomal hydrolysis in heparan sulfate or dermatan sulfate (affects degradation)
Autosomal recessive
-except for Hunter syndrome subtype (X-linked recessive)
Progressive disorder with GAGs accumulating in lysosomes
Oligosaccharides in the urine is present
Causes skeletal and ECM deformities and mental retardation.
Hurler syndrome (MPS 1)
Subtype of mucopolysaccharidoses
Deficient of L-iduronidase (cant degrade dermatan and heparan sulfate)
Affects corneas of eyes and coronary arteries leading to ischemia. Coronal clouding
Treated by bone marrow transplants and enzyme replacement therapy
Most severe form and one of the most common types
Hunter syndrome (MPS 2)
Subtype of mucopolysaccharidoses
iduronate sulfatase deficiency (cant degrade dermatan and heparan sulfate)
X-linked recessive
Mild-severe physical deformities (specifically rashes) No coronal clouding.
Treated via enzyme replacement therapy
One of the most common types
Sanfilippo Syndrome (MPS 3)
Affects various steps of removing sulfate residues from heparan sulfate
Severe nervous system disorders and developmental disorders
No coronal clouding
Sly syndrome (MPS 7)
Glucuronidase deficiency (impairs degradation of dermatan and heparan sulfate)
Hepatosplenomegaly, Skeletal deformity, short store and corneal clouding
