- Most abundant protein in the human body.
- Extensively modified by posttranslational
- Organizes and strengthens extracellular matrix.
- Be (So Totally) Cool, Read Books.
Type I Most common (90%)—Bone (made by osteoblasts), dermis, Tendon, dentin, fascia, cornea, late wound repair (scar tissue). Type I: bone.
↓ production in osteogenesis imperfecta type I.
Type II Cartilage (including hyaline), vitreous body,
Type II: cartwolage. Type III Reticulin—skin, blood vessels, lungs, intestines, bone marrow, lymphatics, uterus, fetal tissue, granulation tissue.
Pliable, stretchy stuff.
Type III: deficient in the uncommon, vascular
type of Ehlers-Danlos syndrome (ThreE D).
Type IV Basement membrane, basal lamina, lens. Type IV: under the floor (basement membrane).
Defective in Alport syndrome; targeted by
autoantibodies in Goodpasture syndrome.
- Collagen synthesis and structure
- Synthesis—translation of collagen α chains (preprocollagen)—usually Gly-X-Y (X and Y are proline or lysine). Glycine content best reflects collagen synthesis (collagen is 1⁄3 glycine).
- Hydroxylation—hydroxylation of specific proline and lysine residues. Requires vitamin C; deficiency → scurvy.
- Glycosylation—glycosylation of pro-α-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen α chains). Problems forming triple helix → osteogenesis imperfecta.
- Exocytosis—exocytosis of procollagen into extracellular space.
- Proteolytic processing—cleavage of disulfide-rich terminal regions of procollagen → insoluble tropocollagen. Problems with cleavage → Ehlers-Danlos syndrome.
- Cross-linking—reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (by copper-containing lysyl oxidase) to make collagen fibrils. Problems with N-terminal propeptide removal → Ehlers-Danlos syndrome. Problems with lysyl oxidase → Menkes disease.
- Osteogenesis imperfecta
- Genetic bone disorder (brittle bone disease) caused by a variety of gene defects (most commonly COL1A1 and COL1A2).
- Most common form is autosomal dominant with ↓ production of otherwise normal type I collagen. Manifestations can include:
- Multiple fractures with minimal trauma (A,B); may occur during the birth process
- Blue sclerae (C) due to the translucent connective tissue over choroidal veins
- Some forms have tooth abnormalities, including opalescent teeth that wear easily due to lack of dentin (dentinogenesis imperfecta)
- Hearing loss (abnormal ossicles)
- May be confused with child abuse.
- Treat with bisphosphonates to ↓ fracture risk.
- Patients can’t BITE:
- Bones = multiple fractures
- I (eye) = blue sclerae
- Teeth = dental imperfections
- Ear = hearing loss
- Ehlers-Danlos syndrome
- Faulty collagen synthesis causing hyperextensible skin (A), hypermobile joints (B), and tendency to bleed (easy bruising).
- Multiple types. Inheritance and severity vary. Can be autosomal dominant or recessive. May be associated with joint dislocation, berry and aortic aneurysms, organ rupture.
- Hypermobility type (joint instability): most common type.
- Classical type (Type I & II) (joint and skin symptoms): caused by a mutation in type V collagen (eg, COL5A1, COL5A2).
- Vascular type (fragile tissues including vessels [eg, aorta], muscles, and organs that are prone to rupture): deficient type III procollagen.
- Menkes disease
- X-linked recessive connective tissue disease caused by impaired copper absorption and transport due to defective Menkes protein (ATP7A). Leads to ↓ activity of lysyl oxidase (copper is a necessary cofactor) ↓ defective collagen.
- Results in brittle, “kinky” hair, growth retardation, and hypotonia.