L7 Structure And Chemistry Of CT Ground Substance Flashcards
What is the ground substance
An amorphous gelatinous material
Its transparent and fills the spaces between fibers and cells. Consists of a large molecule called glycosaminoglycans(GAGs) which link together to form even larger molecules called proteoglycans
What are GAGs
Large complexes of negatively charged heteropysaccharide chains
Generally associated with small amount of protein forming proteoglycans
They have the special ability to bind to large amounts of water and produce a gel like matrix that forms the basis of the body’s ground substance
Hydrated gags serve as a flexible support for the ECM
Structure of gags
Heteropolysaccharide chains composed of a repeating disaccharide unit
Acidic sugar is D-glucoronic acid
Amino sugar is either D-glucosamine or D-galactoseamine
Amino sugar may also be sulfated
Source of sulfates is PAPS
What gives the GAGs its strongly negative nature
Sulfate groups together in presence of the acidic sugar
What is the structure function relationship of GAGS
Due to high conc of -ve charges these heteropolysaccharide chains tend to be extended in solution
Repel each other and are surrounded by shell of water molecules
When brought together they slide past each other much as 2 magnets with the same polarity seem to slide past each other which produces the slippery consistency of mucous and synovial fluid
When GAG is compressed the water squeezes out and gag is forced to occupy smaller volume and gag springs back to hydrated volume due to negative charges repulsion
Contributes to resilience of synovial fluid and vitreous humor of the eye
What are the specific gags
HA Chondroitin sulfate Heparin Keratin sulfate Proteoglycans
Hyaluronic acid
▪️doesnt contain sulfate
▪️not found covalently attached to proteins forming a proteoglycan
▪️polymers are the largest polysaccharides produced by humans
▪️can displace large vol of water
▪️ubiquitous in body tissues and attracts water molecules
▪️plays a key role in lubrication of synovial joints and wound healing processes
Also used for tissue regeneration
Chondroitin sulfate
▪️Most abundant GAG in body
▪️Principally associated with protein to form proteoglycans
▪️sulfation occurs in several positions
▪️found in cartilage,tendons and ligaments and aorta
What is one of leading causes of osteoarthritis
Loss of chondroitin sulfate from articular cartilage in joints leading to inflammation and catabolism of cartilage
Heparin
▪️Unlike other GAGS that are extracellular compounds heparin is an intracellular component of mast cells lining the arteries of lungs,liver and skin
▪️highly sulfated
▪️used as an injectable anticoagulant
Keratin sulfate
▪️Present in cornea,bone and cartilage aggregated with chondroitin sulfates usually associated with protein forming proteoglycans
▪️cornea comprises the richest known source of keratin sulfate in body
▪️plays important role in regulatory development of neural tissue and might have key roles in promotion of axonal repair following injury
Proteogylcans
▪️Found in ECM on outer surface of cells
▪️monomer consists of a core protein to which up to 100 linear chains of GAG are covalently attached. These chains, which may be composed of up to 200 disaccharide units extend out from core protein and remain separated due to charge forming a bottle brush
In which proteogylcans do the species of gag include chondroitin sulfate and keratin sulfate
Cartilage proteoglycans
What is the GAG protein linkage
Covalent linkage is most commonly through a (galactose-galactose-xylose) and a serine residue in the protein
O glycosidic bond is formed between xylose and the hydroxyl group of serine
What is aggregate formation
Many proteoglycan monomers can associate with one molecule of hyaluronic acid to form proteoglycan aggregates
Not covalent occurs through ionic interactions between core protein and hyaluronic acid
Stabilized by additional proteins called link proteins
