Hydroxyproline

Hydroxyproline refers to the hydroxy derivatives of the amino acid proline. The most common forms are trans-4-hydroxyproline and, to a lesser extent, trans-3-hydroxyproline. 4-hydroxyproline is particularly abundant in collagen and gelatin, where hydroxylation occurs after translation.

Biosynthesis and role: Hydroxylation of proline residues in collagen is catalyzed by prolyl hydroxylases, especially prolyl 4-hydroxylase. The reaction requires molecular oxygen, iron(II), ascorbate, and α-ketoglutarate. The enzyme converts specific proline residues to 4-hydroxyproline, a modification essential for stabilizing the collagen triple helix through enhanced hydrogen bonding and interactions with water. This increased stability is critical for the structural integrity of connective tissues.

Occurrence and function: Hydroxyproline is a post-translational modification rather than a genetically encoded amino acid. It is a major component of collagen and contributes to the physical properties of extracellular matrices. 3-hydroxyproline is present at lower levels in some proteins.

Clinical and analytical relevance: Measurement of hydroxyproline in urine or serum serves as an indicator of collagen turnover and bone resorption; elevated levels can be associated with metabolic bone disorders, cancer metastasis, or inflammatory conditions. Hydroxyproline is quantified in clinical chemistry by amino acid analysis, chromatography, or mass spectrometry. Vitamin C deficiency impairs proline hydroxylation, contributing to the symptoms of scurvy.

Summary: Hydroxyproline is a non-encoded, post-translational derivative of proline that is vital for collagen stability and serves as a biomarker for connective tissue metabolism in research and clinical settings.