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. 2023 Jan 26;12:1118675. doi: 10.3389/fonc.2022.1118675

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Copyright © 2023 Phang

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The metabolic link between proline synthesis, collagen formation, formation of free PRO and OH-PRO and epigenetics. Collagen formation by Cancer-associated fibroblasts is linked to biosynthesized proline. The hydroxylation of procollagen, by P4-H exhausts a-KG and ascorbate which decreases demethylation by Tet and Jmj. Free hydroxyproline is formed by early intracellular collagen degradation as well as by extracellular degradation of collagen fibrils. Prolidase is necessary for the hydrolysis of imidodipeptides, i.e. proline and hydroxyproline as C-terminal dipeptides.