PRODH (Proline Dehydrogenase 1)

Additionally, this article discusses the potential of PRODH as a therapeutic target by providing a comprehensive analysis of current therapeutic strategies, including direct and indirect inhibitors. This framework provides a theoretical basis for precise metabolic therapy and combinatorial approaches to overcome therapeutic resistance.

From precursor to fully developed tumors, notable changes include the up-regulation of UCHL1 and MBD3L2, as well as the significant down-regulation of cell-cycle inhibitory genes, CDKN1A, CDKN1C, and CDKN2B, which play roles in cell survival and tumorigenesis. The current study provides insight into SI-NET initiation and progression, offering potential advancements in diagnosis, prevention, and treatment.

These observations align with our in vitro data, reinforcing the modulatory role of proline metabolism in radiosensitivity. While radiotherapy demonstrates robust antitumor effects in prostate cancer, our findings reveal that proline metabolism significantly impairs radiation efficacy in both cellular and animal models.

Our results revealed significant associations between amino acid metabolism gene polymorphisms and PTC risk, suggesting potential biomarkers for PTC susceptibility.

Together, these results reveal that collagen degradation from osteolysis produces Hyp that reinforces osteoclast differentiation and metastasis, creating a vicious cycle. Identification of the role of the PRODH2-SLC7A11/IL-8 axis in promoting breast cancer bone metastasis suggests potential therapeutic strategies to improve patient outcomes.

Therefore, Hyp is involved in several critical metabolic processes regulating DNA synthesis, gene expression, apoptosis/survival, angiogenesis, metastasis and energy production, suggesting a key role of Hyp in reprogramming metabolism of cancer cells. It suggests that Hyp metabolism could be considered as a target in novel experimental strategy for cancer treatment.

Despite its lower inactivation efficiency at the purified bacterial enzyme, S-B32G exhibited comparable activity to NPPG against PRODH and PRODH2 in human cells and mouse livers. Molecular modeling is used to rationalize the stereospecificity of B32G.

In total, thirteen crystal structures with resolutions ranging from 1.32 Å to 1.80 Å were determined, resolving the poses and interactions of seven fragments from the Zenobia library and five analogs of 4-methoxybenzyl alcohol. These results expand the chemical space of probes targeting proline catabolic enzymes and provide new structural information for further inhibitor development.

These findings suggest that PRODH regulates tamoxifen resistance by regulating ferroptosis in tamoxifen-resistant cells.

N-allylglycine, which consists of a glycine recognition module and allyl warhead, is shown to be a covalent inactivator; however, it is less efficient than N-propargylglycine in both enzyme inactivation and cellular assays. Crystal structures of the N-allylglycine-inactivated enzyme are consistent with covalent modification of the N5 by propanal.

Polyamine accumulation in turn stimulated expression of proline dehydrogenase (PRODH) which resulted in mitochondrial hyperactivity and ROS production, culminating in cell toxicity. This work identifies ADO as a unique vulnerability in cancer cells, due to its essential role in maintenance of redox homeostasis through restraining polyamine levels and proline catabolism.

Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.