Biochem Lecture 32: Collagen

collage n

This is the most abundant protein in the body

connective tissues

component of ECM, tendons, cartilage, bones, cornea, gumns

collagen is an important constituent of _______ ______

fibroblasts

collagen is secreted by _______

fibrous proteins (scleroproteins)

proteins that form fibrous structures and provide strength and integrity to a tissue

strain

high tensile strength

elasticity

fibrous proteins are highly resistant to applied ____

gingival connective

collagen fibers are the main constituent of _______ ______ tissue

highly regulated

deposition and degredation of collagen fibers are _____ ______ to maintain a healthy periodontium

alternative splicing

most collagen genes have multiple isoners through ______ _____

COL1A1

_______ gene encodes for a Type I collagen subunit

gums

collagen type I forms the ___

left handed helix (spins counterclockwise)

is collagen a left handed or right handed helix

right

a triple helix of collagen is ____ handed

glycine, proline

each collagen strain is a long ___ and ____ rich sequence

hydroxylated

prolines and lysines are _______ post-translationally

2,1

Three collagen chains, ___ a1 and __ a2 intertwine into the right-handed superhelical triple helix

endo and exo

in proline hydroxylation, the ___ proline and ____ hydroxyproline forms of proline are in equilibrium

exo hydroxyproline

which form must proline be in for the triple helix formation

stability

Loss of hydroxylation leads to dramatic decrease in _____

hydroxy-proline

the formation of _______ _____ is very important

dioxygenase

hydroxylation of prolines is catalyzed by an akg dependent ______

one atom of oxygen is attached to proline and one to the product succinate

what happens in the akg dependent dioxygenase reaction

no

is any external energy source required for the hydroxylation of collagen prolines?

True

True or false: Humans cannot biosynthesize ascorbic acid (Vitamin C)

another reaction takes place, resulting in a heme iron of the enzyme becoming oxidized and inactivated

Vitamin C gives an electron to the iron, regenerating the active form of the enzyme

How does Vitamin C contribute to collagen processing?

Scurvy

A disease associated with Vitamin C deficiency

collagen

causes gums to receed

scurvy leads to shortage of _____

Hydrogen

_____ atoms from glycine allows for very tight packing in the triple helix structure of collagen

intracellulary, secreted

Collagen is synthesized _______, and eventually _____ out of the cell

in and outside

post-transcriptional modifications of collagen occur ___ and _____ the cell

amplifies strength

processing and crosslinking ____ ____ of the collagen fibers

fibrils

triple helices crosslink in a regular pattern to make _____

lysine residues

triple helices are crosslinked together via modified ______ _____

strength

degree of crosslinking affects ______

disease

_____ can arise from anything that interferes with the crosslinked collagen structure

structure

genetic mutations can disrupt the ____ of collagen

replaces glycine center with a bulkier amino acid preventing tight packing

disrupts the inter strand hydrogen bonding - no longer close enough

example of how genetic mutations disrupt the structure of collagen

osteogenesis imperfecta

_______ _____ is an example of a mutation that causes there to be a bulkier amino acid than glycine

D

What can cause a collagen-deficient phenotype?

A. Mutation in the COL1A1 gene that replaces a glycine with a valine

B. Chronic vitamin DC deficiency

C. mutation in the active site of ADAMTS

D. All of the above