L8 Structure And Chemistry Of C.T Fibers

Question 1

What are the types of CT fibers

Answer 1

Collagen and elastic fibers

Question 2

Describe the structure of collagen

Answer 2

Long triple helix of peptide chains known as a chains
A chain are about 1400 residues
Each a chain is coded by a separate mRNA
Every third amino acid is glycine with a very high proportion of proline and lysine in the other 2 positions

Question 3

What is the importance of proline and glycine in collagen

Answer 3

Proline: facilitates formation of helical confirmation of each a chain because its ring structure has kinks in the peptide chain

Glycine: the smallest amino acid and is found every third position as it fits in to restricted places where the 3 helix chains come together

Question 4

What is the function of collagen

Answer 4

Most abundant protein
Found in tissues of high tensile strength and rigidity where collagen resists tensile forces thus providing rigidity to connective tissue

Question 5

Which is hydroxylated more and why

Answer 5

Proline, hydroxyproline residues are imp for collagen folding and stability
50% of proline residues im collagen are hydroxylated

Question 6

What does the extent on hydroxylation depend on

Answer 6

Can vary from 15 to 19% depending on:
Collagen types
From tissue to tissue even within same type of collagen
Under physiological/pathological conditions to tissue

Question 7

What are the steps of collagen synthesis

Answer 7

▪️a chain(pre pro collagen) is first targeted to ER with a signal sequence that is immediately removed by ER
▪️selected proline and lysine residues are hydroxylated in ER to form hydroxylysine and hydroxyproline
▪️pro a chains spontaneously assemble in to pro collagen triple helices within ER
▪️resulting mol has propeptide extensions on both ends still preventing spontaneous assembly in to collagen fibrils
▪️procollagen is translocated from ER in to golgi app and packaged in secretory vesicles
▪️secreted in to ECM by exocytosis
▪️procollagen peptidases remove propeptide ends
▪️procollagen then forms units called tropocollagen which spontaneously assemble in to collagen

Question 8

How is collagen protected from spontaneously assembling in to fibrils

Answer 8

Precursor forms are first synthesized

Question 9

What is needed for hydroxylation

Answer 9

Fe2+ and reducing vit agent C

Question 10

What does collagen look like under the microscope

Answer 10

Packed regularly to form bundles that appear white glistening in the fresh state
When stained with hematoxylin and eosin they appear as ling,wavy pink fiber bundles

Question 11

What are metalloproteins and how are they balanced

Answer 11

Can remodel collagen
Can degrade collagen
Balanced by tissue inhibitor of metalloproteins (TIMP)

Question 12

How are collagen fibers further strengthened

Answer 12

By cross linking between adj lysine side chains by enzyme lysyl oxidase

Question 13

What does cross linking do

Answer 13

Permits scar tissue to strengthen after wound is healed but also contributes to decline in collagen quality with aging causing collagen to stiffen and to decline in vascular elasticity

Question 14

What happens in case of ascorbic acid deficiency (scurvy)

Answer 14

Interchain h bond formation is impaired as is formation of a stable triple helix
Collagen fibrils mat not be cross linked greatly decreasing the tensile strength of assembled fiber
Symptoms: ecchymoses(bruise like) on limbs as a result of subcutaneous extravasation(leakage) Of blood due to capillary fragility

Question 15

What is collagenopathies

Answer 15

Defects in any one of the many steps in collagen fiber synthesis

Question 16

What is ehlers danlos syndrome

Answer 16

Connective tissue disorder caused by a deficiency of collagen processing enzymes (lysyl hydroxylase)
Characterized by skin extensibility and joint hyper mobility
Vascular form is more serious as its associated with potentially lethal arterial rupture

Question 17

What is osteogenesis imperfecta

Answer 17

Brittle bone disease
Genetic disorder
Characterized by bones that fracture easily with minor or no trauma
Due to replacement of glycine by amino acids with bulky side chains

Question 18

What is the function of elastic fibers

Answer 18

Provide elasticity to CT

So abundant in areas such as lungs, walls of arteries and elastic ligaments

Question 19

What is the structure of elastic fibers

Answer 19

Usually slender long and branching in loose connective tissue or form coarser bundles in ligaments and fenestrated sheets

Question 20

What is elastic fibers made of

Answer 20

Rich in proline and lysine but not many hydroxylated

Core is composed of elastin surrounded by sheath of microfibrils which is composed of glycoprotein fibrillin

Question 21

How can elastin be degraded and how is it counteracted

Answer 21

By neutrophils which secrete elastase enzyme

Counteracted by enzyme in the liver a1 antitrypsin

Question 22

What happens to patients with defects in AAT and how is it treated

Answer 22

Emphysema

Can be treated with IV AAT

Question 23

Why can smoking cause emphysema

Answer 23

Methionine residue is essential in AAT for binding to elastase which is vulnerable to oxidation by cigarette smoke

Question 24

What is Marfan syndrome

Answer 24

Defect in gene on chromosome 15
Codes for fibrilin so elastic fibers dont develop normally
Patients typically have tall stature and aortic root dilation
Severely affected: predisposed to fatal rupture of aorta