OtherMMBDiseases ,  Charmian Dawson, Charmane Dawson, Alan Bates Steve Perkins, fibrous proteins

1) Cell secretes 3
chains which form a
PROCOLLAGEN triple
helix.
The chains are held together
by disulphide bridges .
Procollagen contains a lot of
glycine & proline

1.5) An enzyme called
prolyl hydroxylase
converts
proline +
(🍊vitamin C co
factor)→ hydroxyproline

2) This is cleaved by
procollagen
peptidase, forming
tropocollagen (triple
helix but only shown as
one for simplicity)

3) Hydroxyproline has nice OH
groups which form hydrogen
bonds = assembly of
tropocollagen TRIPLE HELIX.
Between each tropocollagen
there are 40nm gaps

4) The enzme lysl oxdiase cross
links tropocollagen chains
together to form a triple helix
The chains are linked together
with aldol links
(between lysine and hydroxylysine)

OSTEOGENESIS

IMPERFECTA

1) 3 chains form a
PROCOLLAGEN
triple helix.
1.5) prolyl hydroxylase
proline → hydroxyproline
(VIT C NEEDED)

2) Cleaved by procollagen
peptidase, forming
tropocollagen
3) Tropocollagen assembly
with OH bonds w/ 40nm
gaps

4) Lysl oxidiase forms aldol
links between two triple
helixes
Type II: prenatal death
(severe forms are
normally recessive)
with multiple fractures

GENETICS: MAY BE DUE TO DOMINANT

NEGATIVE EFFECT
• In COL1A1/COL1A2 gene POINT

MUTATIONS

• Point mutation in a1 and a2 chains of
type 1 collagen
➔Buried Gly –> Cys (just one allele
mutating can affect the whole protein –
MUTATED ALLELE IN COLLAGEN TYPE 1
GENE – disrupts the whole triple helix
fibril!)

Germline mosaicism =

-Mutation randomly occurs in a sex cell -but
then the majority of sex cells will not have
that mutation -therefore offspring will have a
mix of phenotypes – mosaic

Type 1: (dominant
inheritance)
May cause hearing loss,
deformity, impaired tooth
development , impaired
statures, blue sclera (eyes
have a blue tinge) ,
Normal lifespan but
increased risk of fractures
bones) especially tip of
olecranon

❌OSTEOGENESIS IMPERFECTA

Triple helix unfolds = tropocollagen cannot pack nicely
child often presents with frequent fractures (brittle

bones) especially tip of olecranon

EHLER’SDANLOS

SYNDROME

1) 3 chains form a
PROCOLLAGEN
triple helix.
1.5) prolyl hydroxylase
proline
→ hydroxyproline
(VIT C NEEDED)

2) Cleaved by procollagen
peptidase, forming
tropocollagen
3) Tropocollagen assembly
with OH bonds w/ 40nm
gaps

4) Lysl oxidiase forms aldol
links between two triple
helixes

❌Ehlers Danlos
syndrome (type 7)
Reduced procollagen peptidase ,
tropocollagen not FULLY formed.
40nm gaps bw tropocollagen molecules
become blocked by uncleaved peptides
= prevents lysl oxidase forming aldol
links bw Tropocollagen

Very stetchy skin., hypermobile joints,

short stature

SCURVY

1) 3 chains form a
PROCOLLAGEN
triple helix.
1.5) prolyl hydroxylase
proline
→ hydroxyproline
(VIT C NEEDED)

2) Cleaved by procollagen
peptidase, forming
tropocollagen
3) Tropocollagen assembly
with OH bonds w/ 40nm
gaps

4) Lysl oxidiase forms aldol
links between two triple
helixes

❌
s
Curvy (3rd letter of alphabet is C =
stage 3 defect) -No vitamin C
-So no hydroxyproline – No OH groups -So no H bonds form

Haemhorrages and ecchymoses

(bruises)