4-hydroxyproline dehydrogenase (HYPDH)

Hydroxyproline dehydrogenase (HYPDH, also known as hydroxyproline oxidase or encoded by the human gene PRODH2) is an FAD-dependent oxidoreductase enzyme that catalyzes the first step in the degradation of trans-4-hydroxy-L-proline, a major amino acid released during collagen catabolism[6][2][7]. The enzyme specifically oxidizes trans-4-hydroxy-L-proline to (3R,5S)-1-pyrroline-3-hydroxy-5-carboxylate, with a quinone acting as the electron acceptor[6]. This pathway primarily results in the production of glycine and glyoxylate, which contribute to general amino acid and energy metabolism[7]. Defects or alterations in hydroxyproline metabolism are relevant in contexts of bone turnover, tissue degradation, and certain metabolic disorders[7][9]. The enzyme has been identified and studied in diverse organisms, including humans, bacteria (*Pseudomonas putida*, *Pseudomonas aeruginosa*), and is structurally distinct from proline dehydrogenase[1][2]. While not presently a major focus for direct pharmacological targeting, its function underpins key metabolic and diagnostic markers for connective tissue health and disease[7][9].

Other names

Hydroxyproline oxidaseHYPDHPRODH2trans-4-hydroxy-L-proline dehydrogenase

Inhibition would block hydroxyproline catabolism, leading to its accumulation and altered levels of glycine and glyoxylate, potentially disrupting collagen turnover and related pathways.