BI6.1-3 | Extracellular Matrix — Summary & Reflection

REFLECT

A 30-year-old woman presents with multiple joint dislocations from minimal trauma, hyperextensible skin (can stretch the skin of her elbow 8 cm away from the joint), and poor wound healing. She says her father had similar problems.

Using your knowledge of collagen types and synthesis: (1) Which ECM component is most likely defective? (2) Which collagen type would you suspect? (3) What enzyme or cofactor deficiency could cause a similar picture? (4) What single biochemical feature distinguishes Ehlers-Danlos from Marfan syndrome at the molecular level?

KEY TAKEAWAYS

ECM Components:
- Fibrous proteins (collagen, elastin, fibronectin) + GAGs/proteoglycans + adhesive glycoproteins
- Basement membrane: type IV collagen + laminin + perlecan

Collagen:
- Gly-X-Y repeat → triple helix
- Synthesis requires hydroxylation (needs Vitamin C for Fe²⁺ maintenance)
- Scurvy: Vit C deficiency → underhydroxylated collagen → perifollicular haemorrhages, bleeding gums
- Type I: bone/skin (OI with blue sclerae and brittle bones)
- Type III: blood vessels/gut (Ehlers-Danlos vascular — arterial rupture risk)
- Type IV: basement membranes (Alport syndrome — haematuria)

GAGs and Proteoglycans:
- Sulphated GAGs: chondroitin sulphate, heparan sulphate, dermatan sulphate, keratan sulphate, heparin
- Unsulphated: hyaluronic acid (largest; backbone for aggrecan aggregates in cartilage)
- MPS disorders: lysosomal enzyme deficiency → GAG accumulation → multisystem disease
- MPS I (Hurler): α-L-iduronidase; MPS II (Hunter): iduronate-2-sulphatase (X-linked)