Pyrroline-5-carboxylate reductase 1 and Pyrroline-5-carboxylate reductase 2 (PYCR1 (for Pyrroline-5-carboxylate reductase 1), PYCR2 (for Pyrroline-5-carboxylate reductase 2))

Pyrroline-5-carboxylate reductase 1 (PYCR1) and Pyrroline-5-carboxylate reductase 2 (PYCR2) are enzymes that catalyze the final step of proline synthesis, converting pyrroline-5-carboxylate to L-proline using NAD(P)H as a cofactor. These enzymes belong to the oxidoreductase family and possess a Rossmann fold typical for nucleotide-binding domains. PYCR1 and PYCR2 are encoded by nuclear genes and function in mitochondria. They play central roles in cellular metabolism, redox homeostasis, and are essential housekeeping proteins. In cancer, especially breast cancer, PYCR1 is upregulated and contributes to cancer stemness, tumor growth, survival, and poor patient outcomes, making it a significant target for therapeutic intervention and prognostic biomarker discovery. Structural studies show that the enzymes form dimers and utilize conserved domains for their enzymatic action.

Other names

proline oxidaseL-proline oxidase1-pyrroline-5-carboxylate reductaseNADPH-L-Δ1-pyrroline carboxylic acid reductaseL-proline:NAD(P)+ 5-oxidoreductasePYCR1 (gene/protein, human mitochondrial form)PYCR2 (gene/protein, human mitochondrial form)

Drugs (or RNAi approaches) targeting these enzymes would inhibit proline biosynthesis, disrupt cancer cell metabolism and stemness properties, possibly sensitize tumors to stress-induced apoptosis. Modulation of redox balance via intervention in NAD(P)H-dependent reduction reactions. Potential synergy with therapies targeting amino acid metabolism/cancer stem cells.