Pyrroline-5-Carboxylate Reductase 1 (PYCR1) is a mitochondrial enzyme that plays a crucial role in the biosynthesis of proline, an amino acid essential for protein synthesis and cellular metabolism. This enzyme catalyzes the NAD(P)H-dependent conversion of delta1-pyrroline-5-carboxylate (P5C) to proline, which is the final step in proline biosynthesis .
Proline is not only necessary for maintaining normal physiological functions but also plays a special role in the occurrence of tumors. PYCR1 is overexpressed in various cancers, including breast cancer, lung cancer, prostate cancer, and lymphoma . The enzyme’s overexpression is significantly associated with tumor growth, advanced grades, and poor survival of patients .
Recent studies have shown that PYCR1 is involved in the progression of several cancers. Overexpression of PYCR1 is linked to the progression of multiple myeloma, a type of hematological cancer. In multiple myeloma cells, PYCR1 facilitates the conversion of glutamine to proline, contributing to cell survival and drug resistance under hypoxic conditions . Inhibition of PYCR1 has been found to reduce cell viability and proliferation while increasing apoptosis, making it a potential target for cancer therapy .
PYCR1 catalyzes the reduction of delta1-pyrroline-5-carboxylate to proline with the oxidation of NAD(P)H to NAD(P)+ . This enzymatic cycle plays pivotal roles in amino acid metabolism, intracellular redox potential, and mitochondrial integrity . The enzyme is a housekeeping protein, meaning it is essential for the basic maintenance of cellular functions.
Human recombinant PYCR1 is produced using recombinant DNA technology, which involves inserting the human PYCR1 gene into a suitable expression system, such as bacteria or yeast. This allows for the production of large quantities of the enzyme for research and therapeutic purposes. Recombinant PYCR1 is used in various studies to understand its role in cellular metabolism and its potential as a therapeutic target in cancer treatment.