Pyrroline-5-carboxylate reductase 1 (PYCR1) (PYCR1)

Pyrroline-5-carboxylate reductase 1 (PYCR1) is a mitochondrial enzyme that catalyzes the final, NAD(P)H-dependent step in the biosynthesis of proline, converting pyrroline-5-carboxylate (P5C) into L-proline [UniProt P32322; NCBI Gene 5831]. This enzyme plays a dual role in cellular physiology by providing proline for protein synthesis and collagen production while simultaneously regulating the cellular redox state through the regeneration of NAD(P)+ [PMID: 27561554; PMID: 30104363]. In the context of oncology, PYCR1 is frequently overexpressed and functions as a metabolic driver that supports the high proliferative demands of cancer cells, making it a significant target for therapeutic intervention [PMID: 27561554; PMID: 30104363]. Conversely, germline mutations in the PYCR1 gene lead to autosomal recessive cutis laxa type IIB, a condition characterized by premature aging and skin laxity, highlighting its importance in connective tissue integrity [PMID: 19682888]. Current drug discovery efforts focus on small molecule inhibitors and RNA-targeted therapies, such as siRNA or antisense oligonucleotides, to suppress PYCR1 activity in malignant tissues [PMID: 30104363]. While clinical candidates are still in the early stages of development, PYCR1 remains a promising target for metabolic reprogramming strategies in various solid tumors [PMID: 32814554].

Other names

P5C reductase 1P5CR 1PYCRPyrroline-5-carboxylate reductase, mitochondrial

Inhibition of the enzymatic conversion of pyrroline-5-carboxylate to proline, leading to metabolic stress and disruption of cellular redox balance [PMID: 30104363].