Connective Tissue Flashcards
Proteoglycans
Core protein is covalently attached to multiple, long/linear chains of glycosaminoglycans
Where are proteoglycans found?
Synovial fluid, arterial walls, bone/cartilage, ocular virtuous humor, and is a major component of the extra cellular matrix
Functions of proteoglycans
Molecular sieves (due to largeness), give some flexibility to substances
Glycosaminoglycans
Repeating disaccharide units found on proteoglycans Usually contain a hexosamine and uronic acid
How do the types of glycosaminoglycans differ?
Monosaccharides in repeating units change
Which glycosaminoglycan does not link covalently?
Hyaluronic acid
What proteins to 5 of 7 glycosaminoglycans covalently link to?
Serine and Threonine
Which amino acid does keratan sulfate I attach to?
Asparagine
How does hyaluronic acid associate with proteins?
Noncovalent linkage
Synthesis of proteoglycans
- Sugar attaches to serine/threonine
- UPD-sugar glycosyltransferases transfer monosaccharides from nucleotide-linked sugar to receptor
- 2 glycosyltransferases alt adding monosac.
- Sulfate groups added after sugars by PAPS
- Secreted and forms into ECM
Proteoglycan aggregate
Formed by noncovalent interactions b/t the core protein and hyaluronic acid
Glycoproteins
- Usually shorter carb chains than proteoglycans
- Carb portion is usually branched and not made of repeating disaccharides
- Make up most of the proteins circulating in the blood
Glycoprotein synthesis
- Carb monomers are added to protein (lumen of ER/Golgi)
- sugar added via O-linkage (ser, thr) or N-linkage (asn)
- Carb side chain extended by sequential addition of sugar residues to nonreducing end
O-Linked Glycosides
- Begin w/ N-acetyl-galactosamine to specific ser or thr side chain on protein
N-linked Glycosides
- Lipid-linked oligosaccharide is contracted (dolichaol molecules on the membrane)
- sugars added to dolichol by membrane bound glycosyltransferases
- Oligosaccharides transferred from dolichol to asn by protein-oligosaccharide transferase in ER
Degredation of proteoglycans and glycoproteins
- Lysosomes endocytose the molecules
- Glycosidases degrade carb portion of molecules
Endoglycosidase
Cleaves the carb chain to shorter oligosaccharides
Exoglycosidase
Removes sugar residue from the nonreducing end
Collagen Structure
- Triple helix made of 3 alpha chain, left handed helices (3 residues per turn)
- Chains wound together (right handed) and H-bonds stabilize
- Glycine-X-Y is repeated pattern
Proline and hydroxyproline: role in collagen helices
Increases rigidity in collagen helices
Synthesis of Collagen
- Preprocollagen synth. (has a signal sequence and polypeptide extension removed from N&C terminals)
- triple helix formed from C-terminal bc had the ability to form both inter- and intrachain disulfide bonds
Propel hydoxylase
- Hydroxylates the proline molecules, making necessary hydroxyproline
- Vitamin C and α-ketoglutarate are cofactors
Lysine/hydroxylysine
- Formed via Lysyl hydroxylase
- Either lysine or hydrated form can be in Y position
Interruptions
- Areas of globular structures interspersed in the triple helical structure
- Lack Gly-X-Y form
- Ex: Collagen IV
Type I and V of collagen
Skin, bone, tendon, blood vessels, cornea
Type II of Collagen
Cartilage, intervertebral disks, nitrous body
Type III of Collagen
Blood vessels, fetal skin
Type IV of Collagen
Basement membrane
Ehlers-Dalos Syndrome
- Inheritied genetic disorder affecting collagen
- Signs: hyperflexibility of skin, abnormal tissue fragility, increased joint mobility
- 10 types
Type IV of Ehlers-Dalos Syndrome
Most serious type that can cause ruptures of the bowl arteries due to abnormalities in type III collagen
Type VI of Ehlers-Dalos Syndrome
Hysyl hydroxylase deficiency results in joint hypermobility/ocular rupture
Type VIIC of Ehlers-Dalos Syndrome
Procollagen N-proteinase deficiency results in joint hypermobility (from abnormally thin, irregular collagen fibrils)
Alport Syndrome
- x and autosomal linked
- Affects Type IV collagen fibers
- Signs: hematuria, can developed ESRD due t orenal basal abnormaility
Scurvy
- Vitamin C deficiency that affects collagen production (prolysyl and lysyl hydroxylase cofactor)
- Signs: bleeding gums, subcutaneous hemorrhages, poor wound healing
Elastin
Add elastic properties of extensibility and elastic recoil in tissue (stretching without tearing)
Synthesis of Elastin
- synthesized in a single tropoelastin molecule
- No extention peptides in C/N terminals, Gly-X-Y, triple helices, or card portions
Lysyl oxidase
- involved with collagen processing
- Also deanimates lysyl residues from the tropoelastin
Desmosines
- Major cross-link of elastin (CL is unique to elastin)
- 3 lysine-derived aldehydes w/ an unmodified lysine
- CL makes it highly insoluable and extremely stable
Williams syndrome
- Developmental disorder affecting CNS and connective tissue
- 90% of subjects have elastin deletion – Probable cause of aortic stenosis found in condition
Fibrillin
- Large glycoprotein that is a structural component of microfibirls
- Secreted into the ECM to be incorporated into insoluable microfibrils
- Provides a scaffold for deposition of elastion
Marfan Syndrome
- Autosomal dominant – affects connective tissue
- Signs: Tall, long digits, hyperflexibility of joints, cardiovascular problems
- Fibrillin gene is deleted/missense mutations
Fibronectin
- Soluble glycoprotein found in large amounts in the ECM
- Dimmer joined by disulfide bonds near C-terminal
- Arg-Gly-Asp sequence (RGD) that binds to integrin
- 7 binding sites doe heparin, fibrin, collagen, DNA, cell surface proteins
Laminin
- 3 distinct polypeptide chains linked together to form elongated cruciform shape
- Binding site for Collagen IV, heparin, integrin
- Primary component of basal lamina
Basal lamina components
Laminin, enactin, type IV collagen
