Pyrroline-5-Carboxylate Reductase Like (PYCRL) is a member of the pyrroline-5-carboxylate reductase family. This enzyme plays a crucial role in the biosynthesis of proline, an amino acid that serves as a non-enzymatic antioxidant to reduce damage caused by reactive oxygen species (ROS) in microorganisms, animals, and plants .
PYCRL catalyzes the reduction of Δ1-pyrroline-5-carboxylate (P5C) to proline, with the concomitant oxidation of NAD(P)H to NAD(P)+ . This reaction is pivotal in amino acid metabolism, intracellular redox potential, and mitochondrial integrity . The enzyme acts as a homodecamer, meaning it forms a complex of ten subunits, which is essential for its function .
Three human PYCR isoenzymes have been identified: PYCR1, PYCR2, and PYCRL . PYCR1 and PYCR2 are highly similar in amino acid sequence (84%), whereas PYCRL is only 45% similar to the other two forms . PYCR1 and PYCR2 are located in the mitochondria and share structural homology, functioning similarly in the last step of the glutamate-P5C-proline pathway with a preference for NADH as the cofactor . PYCRL, on the other hand, is mainly located in the cytoplasm and prefers to catalyze proline production from ornithine, using NADPH as the cofactor .
Recent studies have highlighted the role of PYCRL in cancer biology. Overexpression of PYCR1 and PYCR2 has been associated with the progression of several cancers . PYCRL, being a part of the same family, is also implicated in promoting cancer growth and inhibiting apoptosis through multiple approaches, including regulating cell cycle and redox homeostasis, and promoting growth signaling pathways . The enzyme’s role in maintaining redox balance and supporting rapid cell proliferation makes it a potential target for cancer therapy .