Category: amino-acid
Aliases: Hyp, 4-Hydroxyproline, trans-4-hydroxy-L-proline
4-Hydroxyproline is not incorporated co-translationally; it is produced post-translationally by prolyl-4-hydroxylase (requires ascorbate, 2-oxoglutarate, O₂, Fe²⁺) on proline residues within newly synthesised pro-collagen, stabilising the triple helix. Released only during collagen turnover, urinary Hyp was historically a bone-resorption marker (now supplanted by CTX/NTX). After oral collagen hydrolysate, plasma Hyp rises as free AA plus Hyp-containing di/tripeptides (Gly-Pro-Hyp, Pro-Hyp) that are resistant to brush-border hydrolysis and absorbed intact via PEPT1. Free Hyp cannot be reused to make new collagen (prolyl hydroxylation is post-translational on Pro, not on free Hyp) — systemic Hyp is catabolised hepatically via 4-hydroxy-2-oxoglutarate aldolase.