Collagen Biochemistry

This lecture will cover

Collagen as a vital connective tissue
protein
Distribution of collagen in nature
The key collagen types
Collagen biosynthesis
Collagen cross-linking and
stabilisation

Most of us are probably aware that

collagen is a widely used cosmetic age

 Collagen is the most abundant

protein in the animal kingdom

6.Major collagen types

Collagen is essential for maintaining

tissue integrity

Whats the proof?

Collagen biosynthesis
INTRACELLULAR EVENTS

Collagen hierarchy

Intracellular processing

Collagen undergoes posttranslational modification

Lysine and proline hydroxylation
Result from lysyl & prolyl hydroxylase
action, ferrous iron, oxygen & ascorbate
Residues provide stability
In case of OH-lysine, they serve as
glycosylation sites and cross-linking sites
OH-lysine glycosylation
Glucosyl & galactosyl transferases
May aid in collagen shipment to ECS

Extracellular processing

Extracellular modifications
N & C-propeptide extensions are
removed
N & C-procollagen proteinases
Reduces solubility, enables fibril
formation
Optimises subsequent cross-linking

Ehlers Danlos
Highly elastic skin In rare cases it can
be fragile Chronic joint pain, joint
laxity Scoliosis Increased risk of bone
fracture Fragile blood vessels Mitral
valve prolapse

Extracellular processing II
Collagen cross-linking

Lysyl oxidase initiates cross-link

formation
Copper containing amine oxidase
Converts the -amino group of lysine
and hydroxylysine to corresponding
aldehydes

Lathyritic agents underpin the critical

importance of collagen cross-links
-aminoproprionitrile

The cross-links of bone & dentine

collagen
The lysyl and hydroxylysyl aldehydes
react with adjacent -amino groups
of other lysine/hydroxylysine
residues KETOAMINES
Bivalent cross-links, 1st phase cross-links
Ketoamines converted to trivalent or 2 nd
phase cross-links by reaction with another
lysyl/hydroxylysyl aldehyde
Pyrrole & pyridinium cross-links

Pyrrole & Pyridinium Crosslinks

Collagen Abnormalities Congenital,

Metabolic & Age-related phenomena

Congenital Osteogenesis imperfecta

The biochemical basis of OI

Metabolic & Age-related alterations

to collagen
Why is collagen vulnerable?
long lived protein
Susceptible to modification
Turnover/renewal and function of tissues
are compromised

Diabetes will result in collagen

changes

Diabetes & collagen

changes
Glycation modified amino acids
e.g., pentosidine, N-carboxymethylarginine

Lipid peroxidation
Malondialdehyde, product of FA
oxidation, also reacts with some
collagen cross-links (Slatter et al. 1999)
Collectively they alter the material
properties (e.g., stiffness) and
proteolytic susceptibility.

N-Carboxymethylarginine

Metabolic bone diseases

What are the changes?

Bone collagen accumulation
Raised bone collagen turnover
Very large increases in PICP
Large increases in catabolic enzymes
Hypomineralised collagen

Cartilage splitting, cartilage loss

Osteoporosis

Pagets Disease