keyword
https://read.qxmd.com/read/38284493/identification-of-the-pyridoxal-5-phosphate-allosteric-site-in-human-pyridox-am-ine-5-phosphate-oxidase
#1
JOURNAL ARTICLE
Anna Barile, Claudio Graziani, Lorenzo Antonelli, Alessia Parroni, Annarita Fiorillo, Martino Luigi di Salvo, Andrea Ilari, Alessandra Giorgi, Serena Rosignoli, Alessandro Paiardini, Roberto Contestabile, Angela Tramonti
Adequate levels of pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6 , and its proper distribution in the body are essential for human health. The PLP recycling pathway plays a crucial role in these processes and its defects cause severe neurological diseases. The enzyme pyridox(am)ine 5'-phosphate oxidase (PNPO), whose catalytic action yields PLP, is one of the key players in this pathway. Mutations in the gene encoding PNPO are responsible for a severe form of neonatal epilepsy. Recently, PNPO has also been described as a potential target for chemotherapeutic agents...
February 2024: Protein Science
https://read.qxmd.com/read/38279347/recent-advances-in-synthesis-of-non-alternating-polyketone-generated-by-copolymerization-of-carbon-monoxide-and-ethylene
#2
REVIEW
Xieyi Xiao, Handou Zheng, Heng Gao, Zhaocong Cheng, Chunyu Feng, Jiahao Yang, Haiyang Gao
The copolymers of carbon monoxide (CO) and ethylene, namely aliphatic polyketones (PKs), have attracted considerable attention due to their unique property and degradation. Based on the arrangement of the ethylene and carbonyl groups in the polymer chain, PKs can be divided into perfect alternating and non-perfect alternating copolymers. Perfect alternating PKs have been previously reviewed, we herein focus on recent advances in the synthesis of PKs without a perfect alternating structure including non-perfect alternating PKs and PE with in-chain ketones...
January 22, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38168036/mouse-models-for-inherited-monoamine-neurotransmitter-disorders
#3
JOURNAL ARTICLE
B Thöny, J Ng, M A Kurian, P Mills, A Martinez
Several mouse models have been developed to study human defects of primary and secondary inherited monoamine neurotransmitter disorders (iMND). As the field continues to expand, current defects in corresponding mouse models include enzymes and a molecular co-chaperone involved in monoamine synthesis and metabolism (PAH, TH, PITX3, AADC, DBH, MAOA, DNAJC6), tetrahydrobiopterin (BH4 ) cofactor synthesis and recycling (adGTPCH1/DRD, arGTPCH1, PTPS, SR, DHPR), and vitamin B6 cofactor deficiency (ALDH7A1), as well as defective monoamine neurotransmitter packaging (VMAT1, VMAT2) and reuptake (DAT)...
January 2, 2024: Journal of Inherited Metabolic Disease
https://read.qxmd.com/read/37820178/importance-of-targeted-next-generation-sequencing-in-pediatric-patients-with-developmental-epileptic-encephalopathy
#4
JOURNAL ARTICLE
Savaş Bariş, Serkan Kırık, Özgür Balasar
OBJECTIVE: Childhood epilepsy is a common neurological disorder with a prevalence of 300-600 cases per 100,000 people. It is associated with refractory epilepsies, global developmental delay, and epileptic encephalopathies, causing epileptic syndromes characterized by cognitive and behavioral disorders. METHODS: In this retrospective cohort study, patients with refractory epilepsy and global developmental delay, defined as epileptic encephalopathy, who applied to the Aydın 7Maternity and Children's Hospital Genetic Diagnosis Center and were followed in the pediatric neurology clinic of our hospital, between July 2018 and July 2021, were included...
2023: Revista da Associação Médica Brasileira
https://read.qxmd.com/read/37751871/protein-protein-interfaces-as-druggable-targets-a-common-motif-of-the-pyridoxal-5-phosphate-dependent-enzymes-to-receive-the-coenzyme-from-its-producers
#5
JOURNAL ARTICLE
Vasily A Aleshin, Victoria I Bunik
Pyridoxal-5'-phosphate (PLP), a phosphorylated form of vitamin B6, acts as a coenzyme for numerous reactions, including those changed in cancer and/or associated with the disease prognosis. Since highly reactive PLP can modify cellular proteins, it is hypothesized to be directly transferred from its donors to acceptors. Our goal is to validate the hypothesis by finding common motif(s) in the multitude of PLP-dependent enzymes for binding the limited number of PLP donors, namely pyridoxal kinase (PdxK), pyridox(am)in-5'-phosphate oxidase (PNPO), and PLP-binding protein (PLPBP)...
July 2023: Biochemistry. Biokhimii︠a︡
https://read.qxmd.com/read/37451483/maintenance-of-cellular-vitamin-b-6-levels-and-mitochondrial-oxidative-function-depend-on-pyridoxal-5-phosphate-homeostasis-protein-plphp
#6
JOURNAL ARTICLE
Jolita Ciapaite, Carlo W T van Roermund, Marjolein Bosma, Johan Gerrits, Sander M Houten, Lodewijk IJlst, Hans R Waterham, Clara D M van Karnebeek, Ronald J A Wanders, Fried J T Zwartkruis, Judith J Jans, Nanda M Verhoeven-Duif
Recently, biallelic variants in PLPBP coding for pyridoxal 5'-phosphate homeostasis protein (PLPHP) were identified as a novel cause of early-onset vitamin B6 -dependent epilepsy. The molecular function and precise role of PLPHP in vitamin B6 metabolism are not well understood. To address these questions we used PLPHP deficient patient skin fibroblasts and HEK293 cells, and YBL036C (PLPHP ortholog) deficient yeast. We showed that independent of extracellular B6 vitamer type (pyridoxine, pyridoxamine or pyridoxal), intracellular PLP was lower in PLPHP deficient fibroblasts and HEK293 cells compared to controls...
July 12, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37428623/on-pathways-and-blind-alleys-the-importance-of-biomarkers-in-vitamin-b-6-dependent-epilepsies
#7
REVIEW
Barbara Plecko
Over the past two decades, the field of vitamin B6 -dependent epilepsies has evolved by the recognition of a growing number of gene defects (ALDH7A1, PNPO, ALPL, ALDH4A1, PLPBP as well as defects of the glycosylphosphatidylinositol anchor proteins) that all lead to reduced availability of pyridoxal 5'-phosphate, an important cofactor in neurotransmitter and amino acid metabolism. In addition, positive pyridoxine response has been observed in other monogenic defects such as MOCS2 deficiency or KCNQ2 and there may be more defects to be discovered...
September 2023: Journal of Inherited Metabolic Disease
https://read.qxmd.com/read/36980111/epilepsy-phenotypes-of-vitamin-b6-dependent-diseases-an-updated-systematic-review
#8
REVIEW
Mario Mastrangelo, Valentina Gasparri, Katerina Bernardi, Silvia Foglietta, Georgia Ramantani, Francesco Pisani
BACKGROUND: Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects). PATIENTS AND METHODS: We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines...
March 15, 2023: Children
https://read.qxmd.com/read/36731270/the-spectrum-of-pyridoxine-dependent-epilepsy-across-the-age-span-a-nationwide-retrospective-observational-study
#9
JOURNAL ARTICLE
Ahmed Jamali, Erle Kristensen, Trine Tangeraas, Vibeke Arntsen, Alma Sikiric, Guste Kupliauskiene, Sverre Myren-Svelstad, Siren Berland, Yngve Sejersted, Thorsten Gerstner, Bjørnar Hassel, Laurence A Bindoff, Eylert Brodtkorb
BACKGROUND: Pyridoxine-dependent epilepsy (PDE) is a rare seizure disorder usually presenting with neonatal seizures. Most cases are caused by biallelic pathogenic ALDH7A1variants. While anti-seizure medications are ineffective, pyridoxine provides seizure control, and dietary interventions may be of benefit. As the natural history beyond adolescence is insufficiently explored, our study aimed to assess the spectrum of PDE at various ages in Norway. METHODS: Patients were ascertained by contacting all Norwegian paediatric, neurological, and neurohabilitation departments and relevant professional societies...
February 2023: Epilepsy Research
https://read.qxmd.com/read/36689703/favorable-propylene-incorporated-terpolymerization-of-ethylene-with-co-mediated-by-cationic-p-o-pd-and-ni-complexes
#10
JOURNAL ARTICLE
Shi-Huan Li, Shi-Yu Chen, Xiao-Bing Lu, Ye Liu
Commercial polyketone materials are generally produced by palladium-catalyzed terpolymerization of ethylene and α-olefin with carbon monoxide (CO), and rare examples were reported regarding the incorporation of propylene into an ethylene/CO copolymer chain using a cost-effective nickel catalyst. In this study, we have developed a series of [P,O]-type cationic Pd and Ni complexes supported by a diphosphazane monoxide (PNPO) platform, and the electronic and steric effect on phosphine, amine, and phosphine oxide moieties is systematically investigated for terpolymerization in terms of activity, propylene/CO (C3) incorporation, and molecular weight control...
January 23, 2023: Inorganic Chemistry
https://read.qxmd.com/read/36614085/elucidating-the-interaction-between-pyridoxine-5-phosphate-oxidase-and-dopa-decarboxylase-activation-of-b6-dependent-enzyme
#11
JOURNAL ARTICLE
Mohammed H Al Mughram, Mohini S Ghatge, Glen E Kellogg, Martin K Safo
Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, serves as a cofactor for scores of B6-dependent (PLP-dependent) enzymes involved in many cellular processes. One such B6 enzyme is dopa decarboxylase (DDC), which is required for the biosynthesis of key neurotransmitters, e.g., dopamine and serotonin. PLP-dependent enzymes are biosynthesized as apo-B6 enzymes and then converted to the catalytically active holo-B6 enzymes by Schiff base formation between the aldehyde of PLP and an active site lysine of the protein...
December 30, 2022: International Journal of Molecular Sciences
https://read.qxmd.com/read/36308585/pyridoxine-dependent-epilepsy-caused-by-a-novel-homozygous-mutation-in-plpbp-gene
#12
JOURNAL ARTICLE
Rojan İpek, Büşra Eser Çavdartepe, Deniz Kor, Çetin Okuyaz
Seizures in newborn infants may be the first finding of hereditary metabolic diseases. Pyridoxine-dependent epilepsy (PDE) is a treatable disorder associated with defects in the one of ALDH7A1, PNPO, or PLPBP genes and it is uncommon but progresses with persistent seizures in the neonatal and infancy period. The seizures are generally resistant to traditional antiepileptic drugs and show a dramatic response to high-dose pyridoxine. In 2016, mutations were reported in PLPBP (previously known as PROSC) gene, which encodes pyridoxal phosphate homeostatic protein (PLPHP)...
October 29, 2022: Metabolic Brain Disease
https://read.qxmd.com/read/36205611/dipteran-endoparasitoid-exorista-bombycis-utilizes-antihemocyte-components-against-host-defense-of-silkworm-bombyx-mori
#13
JOURNAL ARTICLE
Pooja Makwana, Shambhavi P Hungund, Appukuttan Nair R Pradeep
Dipteran endoparasitoids avoid host immune response; however, antidefense components from the Dipterans are unknown. Infestation of commercial silkworm Bombyx mori Linnaeus (Lepidoptera: Bombycidae) by endoparasitoid Exorista bombycis Louis (Diptera: Tachinidae) induced immune reactions, cytotoxicity, granulation, degranulation, and augmented release of cytotoxic marker enzyme lactate dehydrogenase (LDH), and degranulation-mediator enzyme β-hexosaminidase in hemocytes. In this study, by reverse phase high-performance liquid chromatography, fractions of E...
October 7, 2022: Archives of Insect Biochemistry and Physiology
https://read.qxmd.com/read/36106796/analysis-for-variable-manifestations-and-molecular-characteristics-of-pyridox-am-ine-5-phosphate-oxidase-pnpo-deficiency
#14
JOURNAL ARTICLE
Xianru Jiao, Pan Gong, Yue Niu, Zhao Xu, Yuehua Zhang, Zhixian Yang
BACKGROUND: To summarize the clinical and genetic characteristics of patients with pyridox(am)ine-5'-phosphate oxidase (PNPO) deficiency. METHODS: Clinical and genetic data of the patients were collected and analyzed. RESULTS: 18 patients from 17 families with variants in PNPO were collected, and 15 cases survived to date. The age of onset ranged from 1 day to 5 months (median age 6.5 days) and seven of them presented with seizures less than 24 hours...
September 15, 2022: Human Molecular Genetics
https://read.qxmd.com/read/35636100/a-vitamin-a-day-keeps-the-doctor-away-the-need-for-high-quality-pyridoxal-5-phosphate
#15
JOURNAL ARTICLE
N N Stolwijk, M M Brands, L S Smit, V van der Wel, C E M Hollak, C D van Karnebeek
BACKGROUND: A rare subset of vitamin B6 responsive seizure disorders does not respond to pyridoxine, and requires the active form of vitamin B6, pyridoxal-5'-phosphate (PLP), to maintain seizure control. Patients with PLP-responsive seizures are dependent on chronic PLP treatment, yet no licensed PLP product is available. PLP food supplements, a product category regulated less stringently than medication, may prove of insufficient effectiveness and safety. Here we describe and discuss three patient scenarios which illustrate this conundrum...
July 2022: European Journal of Paediatric Neurology: EJPN
https://read.qxmd.com/read/35495162/a-rare-presentation-characterized-by-epileptic-spasms-in-aldh7a1-pyridox-am-ine-5-phosphate-oxidase-and-plpbp-deficiency
#16
JOURNAL ARTICLE
Xianru Jiao, Pan Gong, Yue Niu, Yuehua Zhang, Zhixian Yang
Objective: To analyze the clinical feature, treatment, and prognosis of epileptic spasms (ES) in vitamin B6-dependent epilepsy, including patients with pyridoxine-dependent epilepsy (PDE) caused by ALDH7A1 mutation, pyridox(am)ine-5'-phosphate oxidase ( PNPO ) deficiency, and PLPBP deficiency. Methods: We analyzed data from a cohort of 54 cases with PDE, 13 cases with PNPO deficiency, and 2 cases with PLPBP deficiency and looked for the presentation of ES among them. Results: A total of 11 patients with the seizure presentation of ES have been collected...
2022: Frontiers in Genetics
https://read.qxmd.com/read/35050500/thiamine-dependent-regulation-of-mammalian-brain-pyridoxal-kinase-in-vitro-and-in-vivo
#17
JOURNAL ARTICLE
Victoria Bunik, Vasily Aleshin, Isabel Nogues, Thilo Kähne, Alessia Parroni, Roberto Contestabile, Martino Luigi di Salvo, Anastasia Graf, Angela Tramonti
Vitamins B1 (thiamine) and B6 (pyridox(al/ine/amine)) are crucial for CNS function and neurogenesis due to the coenzyme action of their phosphorylated derivatives in the brain metabolism of glucose and neurotransmitters. Here, the non-coenzyme action of thiamine on the major mammalian producers of pyridoxal-5'-phosphate (PLP), such as pyridoxal kinase (PdxK) and pyridoxine 5'-phosphate oxidase (PNPO), is characterized. Among the natural thiamine compounds, thiamine triphosphate (ThTP) is the best effector of recombinant human PdxK (hPdxK) in vitro, inhibiting hPdxK in the presence of Mg2+ , but activating the Zn2+ -dependent reaction...
January 20, 2022: Journal of Neurochemistry
https://read.qxmd.com/read/34978460/mechanism-of-pyridoxine-5-phosphate-accumulation-in-pyridoxal-5-phosphate-binding-protein-deficiency
#18
JOURNAL ARTICLE
Tomokazu Ito, Honoka Ogawa, Hisashi Hemmi, Diana M Downs, Tohru Yoshimura
The pyridoxal 5'-phosphate (PLP)-binding protein (PLPBP) plays an important role in vitamin B6 homeostasis. Loss of this protein in organisms such as Escherichia coli and humans disrupts the vitamin B6 pool and induces intracellular accumulation of pyridoxine 5'-phosphate (PNP), which is normally undetectable in wild-type cells. This accumulated PNP could affect diverse metabolic systems through the inhibition of some PLP-dependent enzymes. In this study, we investigated the as-yet-unclear mechanism of intracellular accumulation of PNP due to the loss of PLPBP protein encoded by yggS in E...
March 15, 2022: Journal of Bacteriology
https://read.qxmd.com/read/34791208/analysis-of-independent-cohorts-of-outbred-cfw-mice-reveals-novel-loci-for-behavioral-and-physiological-traits-and-identifies-factors-determining-reproducibility
#19
JOURNAL ARTICLE
Jennifer Zou, Shyam Gopalakrishnan, Clarissa C Parker, Jerome Nicod, Richard Mott, Na Cai, Arimantas Lionikas, Robert W Davies, Abraham A Palmer, Jonathan Flint
Combining samples for genetic association is standard practice in human genetic analysis of complex traits, but is rarely undertaken in rodent genetics. Here, using 23 phenotypes and genotypes from two independent laboratories, we obtained a sample size of 3076 commercially available outbred mice and identified 70 loci, more than double the number of loci identified in the component studies. Fine-mapping in the combined sample reduced the number of likely causal variants, with a median reduction in set size of 51%, and indicated novel gene associations, including Pnpo, Ttll6, and GM11545 with bone mineral density, and Psmb9 with weight...
January 4, 2022: G3: Genes—Genomes—Genetics
https://read.qxmd.com/read/34769443/characterization-of-novel-pathogenic-variants-causing-pyridox-am-ine-5-phosphate-oxidase-dependent-epilepsy
#20
JOURNAL ARTICLE
Anna Barile, Philippa Mills, Martino L di Salvo, Claudio Graziani, Victoria Bunik, Peter Clayton, Roberto Contestabile, Angela Tramonti
Several variants of the enzyme pyridox(am)ine 5'-phosphate oxidase (PNPO), responsible for a rare form of vitamin B6 -dependent neonatal epileptic encephalopathy known as PNPO deficiency (PNPOD), have been reported. However, only a few of them have been characterised with respect to their structural and functional properties, despite the fact that the knowledge of how variants affect the enzyme may clarify the disease mechanism and improve treatment. Here, we report the characterisation of the catalytic, allosteric and structural properties of recombinantly expressed D33V, R161C, P213S, and E50K variants, among which D33V (present in approximately 10% of affected patients) is one of the more common variants responsible for PNPOD...
November 6, 2021: International Journal of Molecular Sciences
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