Which amino acid is hydroxylated to form hydroxyproline in collagen, and what is the cofactor required for this post-translational modification?

Explanation

## Post-Translational Hydroxylation of Collagen **Key Point:** Hydroxyproline is formed by hydroxylation of proline residues in the collagen polypeptide chain after translation, not during it. This is a critical post-translational modification that stabilizes the collagen triple helix. ### The Hydroxylation Reaction 1. **Enzyme:** Prolyl hydroxylase (prolyl 4-hydroxylase) 2. **Substrate:** Proline residues in the Y position of collagen's Gly-X-Y tripeptide repeat 3. **Cofactor:** Vitamin C (ascorbic acid) — acts as a reducing agent 4. **Cosubstrates:** α-ketoglutarate, Fe²⁺ 5. **Product:** Hydroxyproline (~10% of collagen amino acids) ### Why Hydroxyproline Matters **High-Yield:** Hydroxyproline stabilizes the collagen triple helix through additional hydrogen bonding. Without adequate vitamin C, insufficient hydroxyproline is formed, leading to defective collagen and scurvy. ### Clinical Correlation: Scurvy **Clinical Pearl:** In vitamin C deficiency (scurvy), prolyl hydroxylase cannot function properly. This results in: - Defective collagen with insufficient hydroxyproline - Unstable triple helix - Poor wound healing, bleeding gums, petechiae, poor bone healing ### Hydroxylysine Formation Separately, lysine residues are also hydroxylated to hydroxylysine by lysyl hydroxylase (also vitamin C-dependent), which serves as attachment sites for carbohydrates and cross-linking. **Mnemonic:** **"CHOP"** — **C**ollagen needs **H**ydroxy modifications; **O**xygen and vitamin **C** required; **P**roline hydroxylated