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The proline metabolism pathway encompasses the biosynthesis and catabolism of proline via enzymes such as proline dehydrogenase (PRODH), pyrroline-5-carboxylate synthase (P5CS), and pyrroline-5-carboxylate reductase (PYCR). Proline is synthesized from glutamate or ornithine through the intermediate P5C, and catabolized to glutamate, feeding into cellular energy production and redox balance. This pathway is crucial for cell survival under stress, collagen synthesis, and adaptation processes. Dysregulation is implicated in cancer progression, host-pathogen interactions, and neurological disease. Therapeutic targeting typically focuses on pathway enzymes, not the overall pathway.
PRODH inhibition impairs proline oxidation, reducing ATP and ROS generation, limiting metastatic and spheroid growth of cancer cells; Inhibition of prolyl-tRNA synthetase limits collagen and proline-rich protein synthesis, activating amino acid stress responses; Inhibition of biosynthesis enzymes (e.g., PYCR1) disrupts redox homeostasis and cell proliferation
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