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Year 2 - Committy 1 - Biochemistry > 3- Biochemistry Of Connective Tissue > Flashcards

3- Biochemistry Of Connective Tissue Flashcards

1
Q

What are the two components of the connective tissue ?

A

1- Inorganic components like hydroxyapatite crystals
2- Organic components like cells, proteins and other biomolecules.

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2
Q

What are the organic components of the connective tissue ?

A

1- cells 2- extracellular matrix : ( structural / fibrous proteins , adhesive glycoproteins , amorphous ground structures )

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3
Q

What is the extracellular matrix (ECM) ?

A

Its a mesh of protein fibers and glycoproteins around the cell provides structural and biochemical support to surroundings cells .

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4
Q

What are fibrillar collagens ?

A

They are the most abundant extracellular matrix proteins that provide tissues and organs with form, stability and connectivity.

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5
Q

How much dose collagen hold of the body’s total protein ?

A

About 25%.

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6
Q

What is the most abundant protein in the human body ?

A

Collagen

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7
Q

Where is the location of collagen ?

A

It is exclusive to the extracellular matrix.

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8
Q

What is collagen made from ?

A

It is a family of proteins made up of similar polypeptides, they are encoded by 34 different genes.

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9
Q

What is the diversity of collagens allow for ?

A

It allows for specialized functions in different tissues.

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10
Q

Where is collagen found in ?

A

It is found in connective tissues in skin, bone, teeth, tendons, ligaments, cartilage and artery walls.

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11
Q

What dose collagen accounts for around one third of all the protein in ?

A

Vertebrates.

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12
Q

What is the most abundant and the prototype of all collagens ?

A

Type I collagen

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13
Q

What 1/3 of amino acids in collagen ?

A

Glycine

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14
Q

What two types of amino acids dose collagen contain ?

A

1- Hydroxyproline ( HO-Pro ).
2- Hydroxylysine ( HO-Lys ).

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15
Q

What is the basic structure of collagen ?

A

It is three polypeptides twists around each other to form a triple helix.

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16
Q

What is the sequence of collagen ?

A

The sequence of Gly-X-Y where X and Y are frequently proline and hydroxyproline.

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17
Q

How is the triple helix stabilized of collagen stabilized by ?

A

(1) hydrogen bond, (2) water bridges between hydroxyls of hydroxyprolines and hydroxylysines and (3) hydrophobic repulsion of imidazole side chains of proline.

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18
Q

What is the collagen molecule subunit tropocollagen ?

A

It is a rod made of three left-handed helices ( distant from the right-handed alpha helix ).

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19
Q

How is collagen distinguished ?

A

It is distinguished by the regular arrangement of amino acids in each of the three chains of collagen subunits.

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20
Q

Where dose glycine nearly always occurs at ?

A

It occurs at every third residue .

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21
Q

What make up about 9% of collagen ?

A

Proline

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22
Q

Why is glycine is critical at every third residue ?

A

Because glycine is the only amino acid small enough to fit in an interior position.

23
Q

Where is the thermal stability of collagen is greater in ?

A

It greater in warm-blooded animals than cold-blooded animals and its correlated with the content of proline and hydroxyproline.

24
Q

What happens when collagen is heated ?

A

It loses its triple helical structure and is converted to amorphous from gelatin

25
Q

What are the 8 steps of collagen synthesis ?

A

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.

26
Q

How are proline and lysine are hydroxylated by dioxygenase ?

A

The are hydroxylated by prolyl- and lysyl hydroxylases.

27
Q

What dose metalloenzymes like prolyl hydroxylase and lysyl hydroxylase require ?

A

They require ferrous iron (fe++) and ascrobic acid (vit c) for activity.

28
Q

How dose O-glycosylation occurs ?

A

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 .

29
Q

Where dose disulfide bonds form ?

A

It forms at the carboxyl end , holding the three chains together and permitting them to wind into a triple helix

30
Q

What happen when the triple-helix formation of collagen ?

A

Its very rapid and stops at glycosylation where procollagen is ready for secretion.

31
Q

What happens at the collagen synthesis pathway ?

A

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.

32
Q

What is the difference between Tropocollagen and procollagen ?

A

Tropocollagen is formed from procollagen by the removal of terminal polypeptides in procollagen by procollagen peptides

33
Q

What is the difference between Tropocollagen and procollagen ?

A

Tropocollagen is formed from procollagen by the removal of terminal polypeptides in procollagen by procollagen peptides ( occurs extracellularly ).

34
Q

What is the final post-translational modification stabilizing and adding mechanical strength to collagen molecule ?

A

Addition of Lysyl oxidase as it converts a specific lysine and hydroxylysine residues to aldehydes.
This form a covalent intermolecular and intramolecular cross-links.

35
Q

What is Lysyl oxidase ?

A

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.

36
Q

Collagen is the major organic component of what ?

A

Bone tissue

37
Q

What is collagen bundles are surrounded by and what is its function ?

A

It is surrounded by a specific calcium and phosphate complex ( hydroxyapatite , Ca^10(PO40^6.(OH^2) ) .
Its function is structural reinforcement .

38
Q

How are collagen fibers formed ?

A

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.

39
Q

What is type IV collagen ?

A

Its a network-producing collagen organized into sheetlike meshwork , its found primarily in the basal lamina.

40
Q

What is the difference between type I and type IV collagen ?

A
  • 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

41
Q

What is collagenases ?

A

The only proteins that can hydrolyze the triple helical structure of collagen.

42
Q

What are the two type of collagenases ?

A

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

43
Q

What is hyperextensible skin ?

A

It is the first disorder related to connective tissue , it was first described by a surgeon in Amsterdam in 1682.

44
Q

What are the metabolic and nutritional diseases that affect the collagen synthesis ?

A

1- vitamin C deficiency (scurvy)
2- drugs and positions
3- metabolic disorders of copper

45
Q

What is the genetic diseases that affect collagen synthesis ?

A

1- osteogenesis imperfecta “brittle bone” : Gly replaced by Cystic in type I collagen
2- Ehlers-danlos syndrome (EDS)

46
Q

What is in the media layer in a typical artery ?

A

Its made up of very organized parallel bundles of smooth tissue and elastin.

47
Q

What dose elastic

A
48
Q

What dose elastic fibers consist of ?

A

Amorphous (elastin) and fibrillar (fibrillin)

49
Q

Why are many organs such as skin, lungs, arteries and ligaments require elasticity ?

A

For tensile strength

50
Q

What dose elastic fibers provide ?

A

It provides the ability to recoil after a stretch allowing many tissues in the body to resume their shape after stretching or contracting.

51
Q

What is the the meaning of amorphous ?

A

without a clearly defined shape or form

52
Q

What is the amorphous component of elastic fibers ?

A

Elastin

53
Q

What is elastin ?

A

It is a hydrophobic protein like collagen with a high content of glycine about 1/3 .

54
Q

How is elastin stabilized ?

A

It is stabilized by the Lysyl oxidase-mediated mechanism but involving only lysine ( not hydroxylysine ) residues

Year 2 - Committy 1 - Biochemistry (4 decks)

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