Ask about this productRelated genes to: PNPO antibody
- Gene:
- PNPO NIH gene
- Name:
- pyridoxamine 5'-phosphate oxidase
- Previous symbol:
- -
- Synonyms:
- PDXPO
- Chromosome:
- 17q21.32
- Locus Type:
- gene with protein product
- Date approved:
- 2004-11-22
- Date modifiied:
- 2014-11-19
Related products to: PNPO antibody
Related articles to: PNPO antibody
- Alcohol abuse is a leading cause of preventable deaths. Alcohol affects brain function and metabolism, including GABA transmission and vitamin B6 (VB6) levels. VB6 is a cofactor for GABA synthesis and degradation; however, the interaction between VB6 deficiency and alcohol consumption remains unknown. We utilized dietary VB6 manipulations and Drosophila models with mutations in pyridox(am)ine-5'-phosphate oxidase (PNPO), a key enzyme in converting dietary VB6 to active VB6, to examine this. Our findings demonstrate that PNPO deficiency reduces alcohol aversion and increases alcohol consumption, whereas alcohol consumption worsens VB6 deficiency, suggesting a vicious cycle. Biochemically, PNPO deficiency and alcohol exposure converge on amino acid metabolism, altering levels of inhibitory neurotransmitters GABA and glycine. Moreover, PNPO deficiency and alcohol exposure synergistically lead to lethality, which can be rescued by low dose but not high dose VB6 supplementation. These results highlight the significance of VB6 in public health, especially in alcohol use and alcohol toxicity. - Source: PubMed
Wang BenjaminFu WenqinUeda AtsushiShah HardikWu Chun-FangChi WanhaoZhuang Xiaoxi - Pyridox(am)ine-5'-phosphate oxidase (PNPO) deficiency is characterized by early-onset epileptic encephalopathy refractory to standard antiseizure medications. It is caused by variants in the gene, resulting in deficient PNPO enzyme activity, which normally converts pyridoxine-5'-phosphate and pyridoxamine-5'-phosphate (two vitamers of vitamin B6) into the active cofactor, pyridoxal-5'-phosphate (PLP). Treatment relies on PLP or pyridoxine in some cases. Long-term outcomes remain suboptimal. We describe two cases of unrelated children treated with vitamin B6 (pyridoxine) in utero: one with a confirmed prenatal PNPO diagnosis and one at risk due to family history but ultimately unaffected. In utero pyridoxine, combined with early postnatal PLP treatment, allowed excellent seizure control and normal neurodevelopment in the long term. Notably, our first patient, treated from birth, is now 10 years old, representing the oldest reported PNPO-deficient individual treated from birth. Case 2 highlights the safety of prenatal B6 supplementation even in unaffected fetuses. These observations support prenatal pyridoxine supplementation as a safe and potentially beneficial strategy in at-risk PNPO pregnancies. - Source: PubMed
Publication date: 2026/04/20
de Puyraimond ChloéPichard SamiaGirard MurielDelanne JulianFaivre LaurenceImbard ApollineBaurand AmandineBenoist Jean-FrançoisMills Philippa BClayton Peter TSchiff Manuel - Multiple myeloma (MM) is a malignancy of plasma cells whose excessive immunoglobulin production elevates reactive oxygen species (ROS), promoting pathogenesis. Active compounds from Traditional Chinese Medicine, such as celastrol, can exert antitumour effects by further increasing ROS levels to toxic levels, thereby inducing apoptosis. Our previous study has demonstrated that pyridoxine-5'-phosphate oxidase (PNPO) is the specific target of celastrol. In this study, we discovered that PNPO, a key enzyme involved in vitamin B6 coenzyme metabolism, is highly expressed in various cancers, including MM. Increased PNPO levels correlated with MM disease progression, promoting cell proliferation and inducing osteoclast differentiation via exosomes. Concurrently, through a structure-based virtual screening workflow targeting critical PNPO residues (R95 and K117), we identified Hetrombopag as a potential PNPO inhibitor. Hetrombopag simultaneously inhibited MM cell proliferation and osteoclast differentiation. Preliminary data from clinical trials also supported the idea that hetrombopag treatment can prolong survival in MM patients. Our research highlights the significant role of PNPO in MM progression and suggests hetrombopag as a promising therapeutic option for MM treatment. - Source: PubMed
Yu TianyiWang ChengXie JingruWei YongxinCui HongweiZhang HuaxiaZhou FanDeng ZhendongYang YeGu Chunyan - Vitamin B6 is an essential micronutrient whose biologically active form, pyridoxal 5'-phosphate (PLP), acts as a cofactor in metabolic reactions linked to tumorigenesis and also functions as an antioxidant. Low plasma PLP levels are consistently associated with cancer, but studies on dietary intake have yielded conflicting results. Overall, evidence suggests that the effects of vitamin B6 deficiency on cancer are context-dependent, varying with cell type and tumor stage. Accordingly, high expression of and , two key genes involved in PLP biosynthesis, is associated with tumor progression in some malignancies, whereas it correlates with improved outcomes in others. This review explores as a useful model to investigate underlying mechanisms, bypassing the limitations of human studies. Research in demonstrates that PLP deficiency promotes cancer by triggering genomic instability. Furthermore, a critical PLP- gene-nutrient interaction impacting oncogenesis has been established in flies, offering significant therapeutic implications. Finally, studies in have shown that PLP deficiency can promote tumor development by also triggering the loss of heterozygosity (LOH). These findings highlight as a powerful tool to elucidate the molecular pathways linking vitamin B6 deficiency to cancer. - Source: PubMed
Publication date: 2026/03/22
Vernì FiammettaAngioli ChiaraFerriero AngeloAgostini Beatrice - Pyridoxal 5'-phosphate (PLP), the coenzyme form of vitamin B, is indispensable for diverse metabolic processes, especially amino acid metabolism. In mammals, PLP is primarily synthesized via a salvage pathway involving pyridoxal kinase (PLK), pyridoxine/pyridoxamine 5'-phosphate oxidase (PNPO), and pyridoxal phosphate phosphatase (PLPP). However, recent evidence suggests the presence of additional, yet unidentified, enzymatic contributors to this pathway. Here, we identify aldo-keto reductase family 1 member C (AKR1C) isozymes as previously unrecognized enzymes involved in vitamin B metabolism. We demonstrate that AKR1Cs catalyze two novel reactions: an NADPH-dependent pyridoxal reductase (PLR) activity that converts pyridoxal (PL) to pyridoxine (PN), and an NADP-dependent pyridoxal dehydrogenase (PLD) activity that oxidizes PL to 4-pyridoxolactone (4-PLA). Both reactions occur under physiological conditions and significantly impact intracellular vitamin B vitamer profiles. Moreover, we show that elevated PL levels suppress AKR1C activities toward non-B substrates, indicating reciprocal cross-talk between vitamin B metabolism and other AKR1C-dependent metabolic processes. This study expands the current framework of mammalian vitamin B metabolism, highlighting AKR1Cs as metabolic hubs with broad regulatory implications. - Source: PubMed
Publication date: 2026/02/25
Kito NayuKitaura YasuyukiIino KyokaToriumi KazuyaNoh HyunahOgawa NaoyaArai MakotoHemmi HisashiIto Tomokazu