Pdxk, or pyridoxal kinase, is a key enzyme in the vitamin B6 salvage pathway, converting inactive B6 vitamers to the active cofactor pyridoxal 5'-phosphate (PLP). PLP is implicated in numerous crucial metabolic reactions, underlining the importance of Pdxk in maintaining normal cellular functions [5,7].

Mutations in PDXK lead to autosomal recessive axonal peripheral polyneuropathy with optic atrophy due to reduced PDXK enzymatic activity and low PLP levels, which can be rescued with PLP supplementation [2,5]. In hepatocellular carcinoma (HCC), upregulated PDXK promotes proliferation and metastasis, and PDXK deficiency facilitates cuproptosis, suggesting it could be a diagnostic and therapeutic target [1]. In serous ovarian cancer, PDXK promotes cell proliferation and is associated with poor prognosis [4]. The natural product P57 induces hypothermia by inhibiting PDXK kinase activity, causing PL accumulation in the hypothalamus [3]. In the context of spinal cord injury, overexpression of PDXK in the motor cortex enhances neuronal growth and locomotor function, while miR-339 targeting PDXK facilitates neurological recovery [6].

In summary, Pdxk is essential for the production of active vitamin B6, which is involved in multiple metabolic reactions. Research on Pdxk, especially through studies of its mutations and functional changes, has revealed its significance in various disease conditions, including neuropathies, cancers, and thermoregulation. These findings provide potential directions for diagnosis, treatment, and further exploration of the underlying molecular mechanisms in these diseases.

References:

1. Chen, Yuqiao, Tang, Lu, Huang, Wentao, Zhang, Gewen, Yao, Lei. 2023. Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma. In Biology direct, 18, 4. doi:10.1186/s13062-023-00358-w. https://pubmed.ncbi.nlm.nih.gov/36750831/

2. Chelban, Viorica, Wilson, Matthew P, Warman Chardon, Jodi, Clayton, Peter T, Houlden, Henry. 2019. PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation. In Annals of neurology, 86, 225-240. doi:10.1002/ana.25524. https://pubmed.ncbi.nlm.nih.gov/31187503/

3. Wang, Ruina, Xiao, Lei, Pan, Jianbo, Yu, Biao, Dang, Yongjun. 2023. Natural product P57 induces hypothermia through targeting pyridoxal kinase. In Nature communications, 14, 5984. doi:10.1038/s41467-023-41435-y. https://pubmed.ncbi.nlm.nih.gov/37752106/

4. Tan, Wei, Liu, Bin, Ling, Huhua. . [Pyridoxal kinase (PDXK) promotes the proliferation of serous ovarian cancer cells and is associated with poor prognosis]. In Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology, 36, 542-548. doi:. https://pubmed.ncbi.nlm.nih.gov/32696745/

5. Keller, Natalie, Mendoza-Ferreira, Natalia, Maroofian, Reza, Wirth, Brunhilde, Karakaya, Mert. 2020. Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism. In Neuromuscular disorders : NMD, 30, 583-589. doi:10.1016/j.nmd.2020.04.004. https://pubmed.ncbi.nlm.nih.gov/32522499/

6. Xiong, Liu-Lin, Qin, Yan-Xia, Xiao, Qiu-Xia, Bai, Xue, Wang, Ting-Hua. 2020. MicroRNA339 Targeting PDXK Improves Motor Dysfunction and Promotes Neurite Growth in the Remote Cortex Subjected to Spinal Cord Transection. In Frontiers in cell and developmental biology, 8, 577. doi:10.3389/fcell.2020.00577. https://pubmed.ncbi.nlm.nih.gov/32793586/

7. Mascolo, Elisa, Barile, Anna, Mecarelli, Lorenzo Stufera, Contestabile, Roberto, Vernì, Fiammetta. 2019. The expression of four pyridoxal kinase (PDXK) human variants in Drosophila impacts on genome integrity. In Scientific reports, 9, 14188. doi:10.1038/s41598-019-50673-4. https://pubmed.ncbi.nlm.nih.gov/31578392/