Collagen Synthesis

Question 1

Collagen Structure

Answer 1

very high amounts of glycine & proline;
Nearly every third amino acid is glycine, critical for formation of a collagen molecule’s triple helix
High tensile strength due to:
1. the compact triple helix
2. the highly ordered polymerization
3. intra- & interchain cross-linking

Question 2

CT Fibroblasts

Answer 2

synthesize collagen & elastin fibers and GAGs, proteoglycans &; glycoproteins of ECM

Active –cytoplasmic processes; large oval nucleus; prominent nucleolus; lots RER; well-dev Golgi.

Quiescent – smaller, spindle-shaped; fewer processes; dark flat nucleus

Question 3

Collagen Synthesis: Intracellular

Answer 3

Intracellular: within fibroblasts: happen within nucleus, ER, Golgi, and secretory vesicles

Question 4

Nucleus of Fibroblast

Answer 4

Formation of mRNA from collagen gene that happens in nucleus, mRNA leaves nucleus to ER where a number of steps take place
mRNA bind to ribosome on ER and synthesis of pro-alpha chains of collagen molecule
Add hydroxyl groups to Gly and Pro AAs

Question 5

rER of Fibroblast

Answer 5

Without addition of hydroxyl groups, the final structure does not form
Need vitamin C; lack of it collagen cannot form and skin cannot heal and bone formation is impaired
Once Gly hydroxylated then we add sugars to them = glycosylation then form pre-procollagen
Once have pre-procollagen then chains will form into triple helix and stabilized by addition of H+ and disulfide bonds plus p47 protein = procollagen (precursor of collagen molecule)

Question 6

Summary of rER

Answer 6

1. Synthesis of alpha chain
2. Add hydroxyls to Pro and Gly
3. Add sugars to make pre-procollagen (glycosylation)
4. Pre-procollagen form a triple helix to make procollagen
5. Stabilized by hydrogen and disulfide bonds

Question 7

Golgi and Secretory Vesicles

Answer 7

From the ER, procollagen molecule goes to Golgi, which packages it into secretory vesicles which are transported into cytoplasm of fibroblasts to the plasma membrane along microtubules and once fuses with membrane the contents are exocytosed

Question 8

Extracellular Steps

Answer 8

Exocytosis of procollagen molecules into the Cove (invagination of cell surface)

Cleavage of the carboxy- and amino- ends by proteinases. Now a collagen molecule.

Polymerization into collagen fibrils with cross-linking

Incorporation of small amounts of other types of collagen

Question 9

Alignment of Collagen Molecules

Answer 9

Extracellular
Align in head to tail arrangement and there will be a gap between the collagen molecules = banding pattern
Fibrils will be bundled into larger collagen fibers and those are bundled into the bundle of collagen fibers = what we can see with a light microscope

Question 10

Clinical Importance

Answer 10

Connective Tissue is able to regenerate after inflammation or injury.

The healing of surgical incisions depends on the reparative capacity of CT.

The fibroblast is the main cell involved in repair.

In tissues with non-dividing cells (i.e., cardiac muscle), the spaces left after injury are filled by CT, forming a scar.