A5061445288- Biochemical and Molecular Research
- Cytomegalovirus and herpesvirus research
- Adenosine and Purinergic Signaling
- Metabolism and Genetic Disorders
- HIV/AIDS drug development and treatment
- Genetics and Neurodevelopmental Disorders
- Folate and B Vitamins Research
- Cancer, Hypoxia, and Metabolism
- Porphyrin Metabolism and Disorders
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Gastroesophageal reflux and treatments
- Genetics, Aging, and Longevity in Model Organisms
- Ubiquitin and proteasome pathways
- Biochemical Analysis and Sensing Techniques
- Autophagy in Disease and Therapy
- Biochemical Acid Research Studies
- Diabetes Treatment and Management
Charles University
2016-2025
General University Hospital in Prague
2016-2024
National Taiwan University Hospital
2024
Abstract A large body of evidence suggests that hypoxia drives aggressive molecular features malignant cells irrespective cancer type. Non-Hodgkin lymphomas (NHL) are the most common hematologic malignancies characterized by frequent involvement diverse hypoxic microenvironments. We studied impact long-term deep (1% O2) on biology lymphoma cells. Only 2 out 6 tested cell lines (Ramos, and HBL2) survived ≥ 4 weeks under hypoxia. The hypoxia-adapted (HA)b Ramos HBL2 had a decreased...
We report for the first time an autosomal recessive inborn error of de novo purine synthesis (DNPS)-PAICS deficiency. investigated two siblings from Faroe Islands born with multiple malformations resulting in early neonatal death. Genetic analysis affected individuals revealed a homozygous missense mutation PAICS (c.158A>G; p.Lys53Arg) that affects structure catalytic site bifunctional enzyme phosphoribosylaminoimidazole carboxylase (AIRC, EC 4.1.1.21)/phosphoribosylaminoimidazole...
Adenylosuccinate lyase (ADSL) functions in de novo purine synthesis (DNPS) and the nucleotide cycle. ADSL deficiency (ADSLD) causes numerous neurodevelopmental pathologies, including microcephaly autism spectrum disorder. ADSLD patients have normal serum levels but exhibit accumulation of dephosphorylated substrates, S-Ado, SAICAr, latter being implicated neurotoxic effects through unknown mechanisms. We examined phenotypic depletion human cells their relation to outcomes. Using specific...
Purines are essential molecules for all forms of life. In addition to constituting a backbone DNA and RNA, purines play roles in many metabolic pathways, such as energy utilization, regulation enzyme activity, cell signaling. The supply is provided by two pathways: the salvage pathway de novo synthesis. Although purine synthesis (PDNS) activity varies during cycle, this represents an important source purines, especially rapidly dividing cells. A method detailed study PDNS lacking analytical...
Phosphoribosylpyrophosphate synthetase (PRPS1) superactivity is an X-linked disorder characterized by urate overproduction Online Mendelian Inheritance in Man (OMIM) gene reference 300661. This condition thought to rarely affect women, and when it does, the clinical presentation mild. We describe a 16-year-old African American female who developed progressive tophi, nephrolithiasis acute kidney failure due overproduction. Family history included mother with tophaceous gout end-stage disease...
The enzymes involved in de novo purine synthesis (DNPS), one of the basic processes eukaryotic cells, transiently and reversibly form a dynamic multienzyme complex called purinosome cytoplasm. has been observed broad spectrum but some studies claim that it is an artefact constructs used for visualization or stress granules resulting from exposure cells to nutrient-reduced growth media. Both may be true depending on method observation. To clarify this point, we combined two previously...
The cellular pool of purines is maintained by de novo purine synthesis (DNPS), recycling and degradation. Mutations in genes encoding DNPS enzymes cause their substrates to accumulate, which has detrimental effects on division organism development, potentially leading neurological impairments. Unspecified symptoms observed many patients could not be elucidated even modern techniques. It presumable that some these problems are induced dysfunctions enzymes. Therefore, we determined the...
Cytotoxicity of de novo purine synthesis (DNPS) metabolites is critical to the pathogenesis three known and one putative autosomal recessive disorder affecting DNPS. These rare disorders are caused by biallelic mutations in DNPS genes phosphoribosylformylglycineamidine synthase (PFAS), phosphoribosylaminoimidazolecarboxylase/phosphoribosylaminoimidazolesuccinocarboxamide (PAICS), adenylosuccinate lyase (ADSL), aminoimidazole carboxamide ribonucleotide transformylase/inosine monophosphate...
Three genetically determined enzyme defects of purine de novo synthesis (PDNS) have been identified so far in humans: adenylosuccinate lyase (ADSL) deficiency, 5-amino-4-imidazole carboxamide-ribosiduria (AICA-ribosiduria), and deficiency bifunctional phosphoribosylaminoimidazole carboxylase phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS). Clinical signs these are mainly neurological, such as seizures, psychomotor retardation, epilepsy, autistic features, etc. This work aims...
<title>Abstract</title> <italic>De novo</italic> synthesis of purines (DNPS) is a biochemical pathway that provides the purine bases for essential biomolecules such as nucleic acids, energy transfer molecules, signaling molecules and various cofactors. Inborn errors DNPS enzymes present with wide spectrum neurodevelopmental neuromuscular abnormalities accumulation characteristic metabolic intermediates in body fluids tissues. In this study, we second case PAICS deficiency due to bi-allelic...
Abstract De novo synthesis of purines (DNPS) is a biochemical pathway that provides the purine bases for essential biomolecules such as nucleic acids, energy transfer molecules, signaling molecules and various cofactors. Inborn errors DNPS enzymes present with wide spectrum neurodevelopmental neuromuscular abnormalities accumulation characteristic metabolic intermediates in body fluids tissues. In this study, we second case PAICS deficiency due to bi-allelic variants gene encoding missense...
Objectives The diagnosis of patients with neurological impairment can be set down only in 2% studied cases. reason might the inability to capture new, date unknown, diseases. One metabolic pathways whose malfunctions could lead is de novo purine synthesis (DNPS). Currently, two genetically determined defects DNPS enzymes, ADSL deficiency and AICA‐ribosiduria, are known. Therefore, existence other manifested by symptoms accumulating intermediates body fluids, highly presumable. Methods We...
Purines are essential molecules for synthesis of nucleic acids, universal carriers chemical energy and parts signaling in all living organisms. Their cellular level is maintained by the de novo purine (DNPS), effective recycling salvage pathway eventual degradation. DNPS includes ten reactions catalyzed six enzymes, four them multifunctional high eukaryotes. Some intermediates unstable and/or toxic, therefore proximity enzymes multienzyme complex called purinosome would be to ensure vital...