3- Biochemistry Of Connective Tissue Flashcards
What are the two components of the connective tissue ?
1- Inorganic components like hydroxyapatite crystals
2- Organic components like cells, proteins and other biomolecules.
What are the organic components of the connective tissue ?
1- cells 2- extracellular matrix : ( structural / fibrous proteins , adhesive glycoproteins , amorphous ground structures )
What is the extracellular matrix (ECM) ?
Its a mesh of protein fibers and glycoproteins around the cell provides structural and biochemical support to surroundings cells .
What are fibrillar collagens ?
They are the most abundant extracellular matrix proteins that provide tissues and organs with form, stability and connectivity.
How much dose collagen hold of the body’s total protein ?
About 25%.
What is the most abundant protein in the human body ?
Collagen
Where is the location of collagen ?
It is exclusive to the extracellular matrix.
What is collagen made from ?
It is a family of proteins made up of similar polypeptides, they are encoded by 34 different genes.
What is the diversity of collagens allow for ?
It allows for specialized functions in different tissues.
Where is collagen found in ?
It is found in connective tissues in skin, bone, teeth, tendons, ligaments, cartilage and artery walls.
What dose collagen accounts for around one third of all the protein in ?
Vertebrates.
What is the most abundant and the prototype of all collagens ?
Type I collagen
What 1/3 of amino acids in collagen ?
Glycine
What two types of amino acids dose collagen contain ?
1- Hydroxyproline ( HO-Pro ).
2- Hydroxylysine ( HO-Lys ).
What is the basic structure of collagen ?
It is three polypeptides twists around each other to form a triple helix.
What is the sequence of collagen ?
The sequence of Gly-X-Y where X and Y are frequently proline and hydroxyproline.
How is the triple helix stabilized of collagen stabilized by ?
(1) hydrogen bond, (2) water bridges between hydroxyls of hydroxyprolines and hydroxylysines and (3) hydrophobic repulsion of imidazole side chains of proline.
What is the collagen molecule subunit tropocollagen ?
It is a rod made of three left-handed helices ( distant from the right-handed alpha helix ).
How is collagen distinguished ?
It is distinguished by the regular arrangement of amino acids in each of the three chains of collagen subunits.
Where dose glycine nearly always occurs at ?
It occurs at every third residue .
What make up about 9% of collagen ?
Proline
Why is glycine is critical at every third residue ?
Because glycine is the only amino acid small enough to fit in an interior position.
Where is the thermal stability of collagen is greater in ?
It greater in warm-blooded animals than cold-blooded animals and its correlated with the content of proline and hydroxyproline.
What happens when collagen is heated ?
It loses its triple helical structure and is converted to amorphous from gelatin
What are the 8 steps of collagen synthesis ?
1- translation of pre-procollagen on membrane-bound polyribosomes.
2- removal of signal peptide giving procollagen.
3- hydroxylation of prolin and lysine residues by prolyl- and lysyl-hydroxylases.
4- O-Glycosylation of some HO-lysine by galactosyl- and glucosyl transferases.
5-disulfide bond formation intrachain (at N-ends) and interchain (at C-ends).
6- Triple helix formation ( proceeds from C- to N-terminus in zipper-like fashion )
7- Triple-helix formation stops glycosylation
8- secretion of the procollagen triple-helix int the extracellular space.
How are proline and lysine are hydroxylated by dioxygenase ?
The are hydroxylated by prolyl- and lysyl hydroxylases.
What dose metalloenzymes like prolyl hydroxylase and lysyl hydroxylase require ?
They require ferrous iron (fe++) and ascrobic acid (vit c) for activity.
How dose O-glycosylation occurs ?
By the consecutive reaction of two transverse:
1- a galactose from UDP-gal transferred to the hydroxyl of the OH-lys from its first carbon by galactosyl transferase .
2- a glucose from UDP-Glucose is transferred to the second hydroxyl of the attached galactose from its first hydroxyl by glucosyl transferase .
Where dose disulfide bonds form ?
It forms at the carboxyl end , holding the three chains together and permitting them to wind into a triple helix
What happen when the triple-helix formation of collagen ?
Its very rapid and stops at glycosylation where procollagen is ready for secretion.
What happens at the collagen synthesis pathway ?
The procollagen with N and C terminal Cleavage domains is secreted into the extracellular space into the extracellular space by fibroblasts.
The N and C terminal chains are cleaved by peptides resulting in a tropocollagen.
The peptides then self-assembly into fibrils.
What is the difference between Tropocollagen and procollagen ?
Tropocollagen is formed from procollagen by the removal of terminal polypeptides in procollagen by procollagen peptides
What is the difference between Tropocollagen and procollagen ?
Tropocollagen is formed from procollagen by the removal of terminal polypeptides in procollagen by procollagen peptides ( occurs extracellularly ).
What is the final post-translational modification stabilizing and adding mechanical strength to collagen molecule ?
Addition of Lysyl oxidase as it converts a specific lysine and hydroxylysine residues to aldehydes.
This form a covalent intermolecular and intramolecular cross-links.
What is Lysyl oxidase ?
Its a copper-dependent amine oxidase that plays a critical role in biogenesis of connective tissue matrices by crosslinking the extracellular matrix proteins, collagen and elastin.
Collagen is the major organic component of what ?
Bone tissue
What is collagen bundles are surrounded by and what is its function ?
It is surrounded by a specific calcium and phosphate complex ( hydroxyapatite , Ca^10(PO40^6.(OH^2) ) .
Its function is structural reinforcement .
How are collagen fibers formed ?
The lateral interactions of triple helices of collagens result in the formation of fibrils, the packing of collagen is such adjacent molecules are displaced approximately 1/4 of their length (67nm). This is produces a striated effect that can be seen in the electron microscope.
What is type IV collagen ?
Its a network-producing collagen organized into sheetlike meshwork , its found primarily in the basal lamina.
What is the difference between type I and type IV collagen ?
- Type I:
1-organization into rope like structure, which provides high tensile strength.
2- helical portion continues (rod-like)
3-poly peptides removed after secretion
4-molecules lineup in a parallel area.
-Type IV:
1-interwoven with extra cellular metrics components to form basil lamina
2- helical portion interrupted, allowing bends
3- molecules lineup in an antiparallel fashion
What is collagenases ?
The only proteins that can hydrolyze the triple helical structure of collagen.
What are the two type of collagenases ?
1- endogenous / mammalian collagenase which is essential biological mechanism that regulates matrix remodeling and encourages normal turnover of tissue and removal of dead tissue.
2- Bacterial (clostridial) collagenase causes a disease “gas gangrene“ (myonecrosis) cleaves the collagen molecule at multiple sites along the triple helix
What is hyperextensible skin ?
It is the first disorder related to connective tissue , it was first described by a surgeon in Amsterdam in 1682.
What are the metabolic and nutritional diseases that affect the collagen synthesis ?
1- vitamin C deficiency (scurvy)
2- drugs and positions
3- metabolic disorders of copper
What is the genetic diseases that affect collagen synthesis ?
1- osteogenesis imperfecta “brittle bone” : Gly replaced by Cystic in type I collagen
2- Ehlers-danlos syndrome (EDS)
What is in the media layer in a typical artery ?
Its made up of very organized parallel bundles of smooth tissue and elastin.
What dose elastic
What dose elastic fibers consist of ?
Amorphous (elastin) and fibrillar (fibrillin)
Why are many organs such as skin, lungs, arteries and ligaments require elasticity ?
For tensile strength
What dose elastic fibers provide ?
It provides the ability to recoil after a stretch allowing many tissues in the body to resume their shape after stretching or contracting.
What is the the meaning of amorphous ?
without a clearly defined shape or form
What is the amorphous component of elastic fibers ?
Elastin
What is elastin ?
It is a hydrophobic protein like collagen with a high content of glycine about 1/3 .
How is elastin stabilized ?
It is stabilized by the Lysyl oxidase-mediated mechanism but involving only lysine ( not hydroxylysine ) residues
