Collagen Synthesis and Vitamin C

Gene Transcription & Translation

Preprocollagen is synthesized on ribosomes of the Rough Endoplasmic Reticulum (RER) with a signal peptide.

Cleavage of Signal Peptide

The signal sequence is cleaved to yield procollagen containing terminal propeptides

Hydroxylation (Vitamin C Dependent)

Specific Proline and Lysine residues on procollagen are hydroxylated by the enzymes Prolyl Hydroxylase and Lysyl Hydroxylase to form hydroxyproline and hydroxylysine.

Role of Vitamin C

These hydroxylase enzymes require ferrous iron (Fe^2+) as a cofactor. During the reaction, Fe^2+ is oxidized to ferric iron (Fe^3+), inactivating the enzyme. Ascorbic Acid acts as a reducing agent, donating an electron to convert Fe^3+ back to active Fe^2+

_{^{Without Vitamin C, unhydroxylated procollagen cannot form stable interstrand hydrogen bonds}}

Glycosylation & Triple Helix Formation

• Hydroxylysine residues undergo glycosylation with glucose and galactose

• Three procollagen chains wrap around each other to form a stable triple-helix (Procollagen) held together by hydrogen bonds

Secretion

Procollagen is packaged into vesicles by the Golgi apparatus and secreted into the extracellular matrix

Cleavage of Propeptides

Extracellular Procollagen Peptidases cleave the non-helical N-terminal and C-terminal ends of procollagen, converting it into insoluble Tropocollagen

Cross-Linking (Fibril Formation - Copper Dependent)

• ropocollagen molecules spontaneously self-assemble into collagen fibrils.

• The enzyme Lysyl Oxidase covalently cross-links tropocollagen molecules via oxidative deamination of lysine and hydroxylysine residues.

• Cofactor Requirement: Lysyl Oxidase requires Copper (Cu^2+). Defective copper transport leads to Menkes Disease (k*nky hair, w*ak collagen)