72. Biochemistry of Connective Tissue Proteins: Collagens. Metabolism of hexosamines. Structure of Glycosaminoglycans.

Biochemistry of Connective Tissue Proteins – Collagens

• Collagen is the main structural protein in connective tissues (skin, bone, cartilage, tendons, cornea, blood vessels).
• It provides tensile strength, stability, and resistance to stretching.
• The basic unit of collagen is tropocollagen, which consists of three polypeptide α-chains twisted into a triple helix.
• The repeating amino acid sequence is Gly–X–Y, where X is often proline and Y is often hydroxyproline or hydroxylysine.
• Glycine is essential because it is the smallest amino acid, allowing tight packing of the triple helix.
• Collagen is exceptionally rich in proline and hydroxyproline which stabilize the helix and depend on Vitamin C for hydroxylation.

Biosynthesis of Collagen

Occurs partly in fibroblasts (intracellular) and partly extracellularly:

• Synthesis begins with preprocollagen in rough ER.
• Proline and lysine residues are hydroxylated (requires Vitamin C, Fe²⁺, O₂).
• Deficiency of Vitamin C prevents hydroxylation → weak collagen → scurvy.
• Some hydroxylysine residues are glycosylated.
• Chains assemble → procollagen (triple helix with loose ends).
• Procollagen is secreted outside the cell.
• Procollagen peptidase cleaves terminal peptides → tropocollagen.
• Tropocollagen molecules arrange in fibrils and are covalently cross-linked by lysyl oxidase (requires copper).
• Deficiency of copper or lysyl oxidase leads to weak connective tissue (e.g., Menkes disease, Ehlers–Danlos syndrome).