Proline dehydrogenase 1, mitochondrial (PRODH) (PRODH)

Proline dehydrogenase 1, mitochondrial (PRODH), also known as proline oxidase (POX), is a flavin-dependent enzyme located on the inner mitochondrial membrane that catalyzes the first and rate-limiting step of proline catabolism (UniProt P12788). It converts L-proline into (S)-delta-1-pyrroline-5-carboxylate (P5C), a reaction coupled to the reduction of ubiquinone in the electron transport chain, which can lead to the generation of reactive oxygen species (ROS) (NIH/PubMed 1.1.4). PRODH is a p53-inducible gene (PIG6) and plays a dual role in cancer: it can act as a tumor suppressor by inducing ROS-mediated apoptosis or as a survival factor by providing energy and metabolic intermediates under stress (Frontiers in Oncology 1.3.5). Genetic variations and deletions in the PRODH gene, particularly at the 22q11.2 locus, are strongly associated with susceptibility to schizophrenia and cognitive deficits (MedlinePlus 1.3.2, NIH/PubMed 1.4.2). Furthermore, mutations in PRODH cause hyperprolinemia type I, a condition characterized by elevated plasma proline levels which may have neurotoxic effects (NIH/PubMed 1.4.2). Therapeutic strategies targeting PRODH include the use of competitive inhibitors like L-tetrahydrofuroic acid and suicide inhibitors like N-propargylglycine, which are being investigated for their potential to exploit metabolic vulnerabilities in various malignancies (AACR Journals 1.2.2). The enzyme's involvement in both metabolic reprogramming and neuropsychiatric health makes it a complex but promising target for drug development. Research continues to explore how modulating PRODH activity can balance its apoptotic and survival-promoting functions in a context-dependent manner.

Other names

Proline oxidasePOXPRODH1p53-induced gene 6 proteinPIG6HSPOXSCZD4

Inhibition of the enzymatic conversion of L-proline to delta-1-pyrroline-5-carboxylate to modulate cellular redox state, ROS production, and metabolic flux.