Hydroxyproline dehydrogenase (HYPDH)

Hydroxyproline dehydrogenase (HYPDH, also historically known as proline dehydrogenase 2, PRODH2, and hydroxyproline oxidase) is a mitochondrial FAD-dependent enzyme that catalyzes the initial and rate-limiting step in the catabolism of trans-4-hydroxy-L-proline, converting it to Δ¹-pyrroline-3-hydroxy-5-carboxylate with ubiquinone-10 as the physiological electron acceptor. The enzyme is highly specific for hydroxyproline and is involved in collagen turnover and energy metabolism, linking amino acid breakdown to the mitochondrial electron transport chain. Dysfunction or overactivity in the pathway involving HYPDH/PRODH2 can contribute to excessive glyoxylate and oxalate production, promoting kidney stone formation in conditions such as primary hyperoxaluria; therefore, it is considered a promising drug target for the treatment of this metabolic disorder. Research has identified experimental inhibitors, but no approved drugs target HYPDH in clinical use as of 2024.

Other names

PRODH2Proline dehydrogenase 2Kidney and liver proline oxidase 1Probable proline dehydrogenase 2Probable proline oxidase 2Hydroxyproline dehydrogenaseHydroxyproline oxidaseHsPOX1HSPOX1HYPDH

Inhibition of hydroxyproline dehydrogenase activity to reduce the generation of glyoxylate, aiming to decrease oxalate accumulation and treat primary hyperoxaluria