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Proline metabolism pathway

Molecular classification
Enzyme (for individual components: PRODH, P5CS, PYCR1/2, etc.), Metabolic pathway (for the pathway as a whole)
01

Overview

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.

Other names
Proline metabolic pathwayProline-P5C cycleProline biosynthesis and catabolism pathway
02

Mechanism of action

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

03

Biological functions

Energy homeostasisCellular redox regulationStress adaptationCollagen biosynthesisCell proliferation and survival (primarily via cancer enzyme roles)Apoptosis (via regulation by p53 and ROS)
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Disease associations

Cancer (especially metastasis and tumor growth via PRODH and PYCR1)Neurodegenerative diseasesInfection and host-pathogen interactionsOther: Cardiovascular and metabolic disorders, stress-related pathologies
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Safety considerations

Inhibition may affect normal cell energy and stress responses, but specific inhibitors (e.g., L-THFA) showed low toxicity in preclinical modelsEffects on collagen synthesis and overall amino acid balancePotential risk for impaired redox homeostasis
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Interacting drugs

L-tetrahydro-2-furoic acid (L-THFA) (PRODH inhibitor)

5 more in the full profile.

07

Biomarkers

High expression of PYCR1, P5CS (ALDH18A1), and altered proline pathway flux are biomarkers for cancer vulnerability and metabolic phenotype (especially in neuroblastoma, breast cancer, Burkitt lymphoma)Proline, P5C levels, and related gene expression (PRODH, PYCR1/2)

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