STEPTRACKERBIOCHEMISTRY + PATHOLOGY + GENETICS | CELL BIOLOGY | HIGH-YIELD REVIEW

Collagen

Know the types by location, the synthesis steps inside and outside the cell, and the disease that follows each broken step.

FOCUS ON
Collagen = Gly-X-Y repeats (X/Y often proline, hydroxyproline, hydroxylysine). Inside the fibroblast: translation (RER) → hydroxylation (vitamin C → scurvy) → glycosylation → triple helix (OI if defective). Outside: propeptide cleavage (EDS dermatosparaxis) → lysyl oxidase cross-links (copper → Menkes). Type I bone · II cartilage · III reticulin/vessels · IV basement membrane.
TYPE · STEP
LOCATION · WHAT HAPPENS
DEFECT → DISEASE
CLUE
Type I
most abundant
Bone, skin, tendon, dentin, fascia, cornea, late wound repair
↓ production → osteogenesis imperfecta
Bone, skin, tendon
Type II
Cartilage (hyaline), vitreous body, nucleus pulposus
Some chondrodysplasias
Cartilage, vitreous
Type III
Reticulin: skin, blood vessels, uterus, fetal tissue, early granulation tissue
Vascular EDS (COL3A1)
Vessels, granulation tissue
Type IV
Basement membrane, lens
Alport (α5 chain) · Goodpasture (antibodies to α3)
Basement membrane
1. Translation
Preprocollagen α chains (Gly every third residue) made on RER
Glycine substitution mutations → OI
Glycine is the smallest residue → fits inside the helix
2. Hydroxylation
Proline and lysine hydroxylated in RER; needs vitamin C, Fe²⁺, O₂
Scurvy: gum bleeding, perifollicular hemorrhage, corkscrew hairs, poor wound healing
Tea-and-toast diet, elderly
3. Glycosylation & triple helix
Hydroxylysines glycosylated; three α chains wind into procollagen (disulfide-linked C-propeptides)
Defective helix → osteogenesis imperfecta
Mostly COL1A1/COL1A2, autosomal dominant
4. Secretion & cleavage
Procollagen exocytosed; peptidases trim N- and C-terminal propeptides → tropocollagen
Some EDS types (procollagen peptidase)
—
5. Cross-linking
Lysyl oxidase (copper-dependent) links lysines → fibrils with tensile strength
Menkes (ATP7A, X-linked): kinky brittle hair, hypotonia, growth delay, ↓ serum copper and ceruloplasmin
Also many EDS and vascular weakness
Osteogenesis imperfecta
Abnormal type I collagen
Multiple fractures with minimal trauma, blue sclerae, hearing loss (ossicles), dental defects (dentinogenesis imperfecta)
Can mimic child abuse
Ehlers-Danlos syndrome
Faulty collagen processing or structure
Hyperextensible skin, hypermobile joints, easy bruising; vascular type → arterial, bowel, uterine rupture; berry aneurysms, MVP
Classic (type V collagen), hypermobility (most common), vascular (type III)

Mechanism — collagen assembly line

Translate α chainRER
→
HydroxylateVit C · scurvy
→
Glycosylate
→
Triple helixOI
Exocytose procollagen
→
Cleave propeptidesEDS
→
Lysyl oxidase cross-linksCu · Menkes
→
Fibril

Look-alike collagen disorders

DISEASE
STEP
KEY SIGN
INHERITANCE
Scurvy
Hydroxylation
Bleeding gums, corkscrew hairs
Dietary
OI
Triple helix (type I)
Fractures, blue sclerae
AD (mostly)
EDS
Processing/structure
Stretchy skin, loose joints
Mostly AD
Menkes
Cross-linking (Cu)
Kinky hair, neurodegeneration
XR

How it's tested

COMMON CONFUSIONBlue sclerae + fractures = OI; stretchy skin + loose joints = EDS. Both can present as "suspected child abuse."
THE TRAPMenkes is copper deficiency at the tissue level with low serum copper and ceruloplasmin — the opposite of Wilson disease (copper overload).
YOUR APPROACHFind the step (inside vs outside the cell) → cofactor (vitamin C, copper) or gene → disease.

If you see… think…

Child with many fractures and blue sclerae → osteogenesis imperfecta (type I)
Bleeding gums, corkscrew hairs, poor healing → scurvy (hydroxylation)
Boy with kinky brittle hair, hypotonia, low ceruloplasmin → Menkes (lysyl oxidase)
Hyperextensible skin, easy bruising, joint dislocations → Ehlers-Danlos
Young adult with spontaneous arterial or bowel rupture → vascular EDS (type III)
Hematuria, deafness, lens problems → Alport (type IV)
Antibodies to the α3 chain of type IV → Goodpasture
Collagen of cartilage and vitreous → type II
Granulation tissue collagen replaced later by → type I (from type III)
Every third residue in collagen → glycine