A5031721914- Pharmacogenetics and Drug Metabolism
- Hormonal Regulation and Hypertension
- Drug Transport and Resistance Mechanisms
- Hormonal and reproductive studies
- Sexual Differentiation and Disorders
- Biochemical and Molecular Research
- Genomics and Rare Diseases
- Pharmacological Effects and Toxicity Studies
- Computational Drug Discovery Methods
- Estrogen and related hormone effects
- Metabolomics and Mass Spectrometry Studies
- Gene expression and cancer classification
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Growth Hormone and Insulin-like Growth Factors
- Diet, Metabolism, and Disease
- Enzyme Structure and Function
- Metabolism and Genetic Disorders
- Renal Transplantation Outcomes and Treatments
- Digestive system and related health
- Adrenal Hormones and Disorders
- Aldose Reductase and Taurine
- Genetics and Neurodevelopmental Disorders
- Chemical Reactions and Isotopes
- Inflammatory mediators and NSAID effects
- Folate and B Vitamins Research
University of Bern
2019-2024
University Children’s Hospital Bern
2019-2024
University Hospital of Bern
2023-2024
Universidad Nacional de Asunción
2019-2020
Instituto de Investigaciones en Ciencias de la Salud
2019
Temple Street Children's University Hospital
2019
Uniwersytecki Szpital Dziecięcy
2019
Children's Clinical University Hospital
2019
Metabolic control is mediated by the dynamic assemblies and function of multiple redox enzymes. A key element in these assemblies, P450 oxidoreductase (POR), donates electrons selectively activates numerous (>50 humans >300 plants) cytochromes (CYPs) controlling metabolism drugs, steroids xenobiotics natural product biosynthesis plants. The mechanisms underlying POR-mediated CYP remain poorly understood to date no ligand binding has been described regulate specificity POR. Here, using a...
Twenty new compounds, targeting CYP17A1, were synthesized, based on our previous work a benzimidazole scaffold, and their biological activity evaluated. Inhibition of CYP17A1 is an important modality in the treatment prostate cancer, which remains most abundant cancer type men. The assessment included hydroxylase lyase inhibition, CYP3A4 P450 oxidoreductase (POR) as well antiproliferative PC3 cells. potent compounds selected for further analyses including silico modeling. This combined...
Cytochromes P450 located in the endoplasmic reticulum require NADPH cytochrome oxidoreductase (POR) for their catalytic activities. Mutations POR cause multiple disorders humans related to biosynthesis of steroid hormones and also affect drug-metabolizing Electron transfer occurs from NADH FAD FMN, flexible hinge region is essential domain movements bring FMN close together electron transfer. We tested effect variations check if effects would be similar across all redox partners or there...
Mutations in cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We report novel R550W mutation POR identified 46,XX patient with signs aromatase deficiency.Analysis deficiency from the POR.Both child and mother had virilization. Ultrasound revealed presence uterus ovaries. No defects CYP19A1 were found, but further analysis targeted Disorders Sexual Development NGS panel (DSDSeq.V1, 111 genes) on NextSeq (Illumina) platform Madrid Barcelona, Spain,...
Cytochrome P450 oxidoreductase (POR) is the redox partner of steroid and drug-metabolising cytochromes located in endoplasmic reticulum. Mutations POR cause a broad range metabolic disorders. The variant rs17853284 (P228L), identified by genome sequencing, has been linked to lower testosterone levels reduced activities. We expressed wild type P228L bacteria, purified proteins, performed protein stability catalytic functional studies. Variant affected as evidenced unfolding temperatures...
Rabson–Mendenhall syndrome (RMS) is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We report the first case of RMS Paraguayan patient. The patient 6-year-old girl who presented with hypertrichosis, acanthosis nigricans, nephrocalcinosis, and elevated levels glucose that served as diagnostic indicators for RMS. Genetic testing next-generation sequencing (NGS) revealed two pathogenic variants exons 2 19 INSR gene:...
This study reports on the synthesis and evaluation of novel compounds replacing nitrogen-containing heterocyclic ring chemical backbone structure cytochrome P450 17α-hydroxylase/12,20-lyase (CYP17A1) inhibitors with a phenyl bearing sulfur-based substituent. Initial screening revealed marked inhibition CYP17A1 activity. The selectivity was thereafter determined against 21-hydroxylase, 3A4, oxidoreductase. Additionally, showed weak inhibitory activity aldo-keto reductase 1C3 (AKR1C3)....
Cytochrome P450 oxidoreductase (POR) is an essential redox partner for steroid and drug-metabolizing cytochromes located in the endoplasmic reticulum. Mutations POR lead to metabolic disorders, including congenital adrenal hyperplasia, affect metabolism of steroids, drugs, xenobiotics. In this study, we examined approximately 450 missense variants gene listed Genome Aggregation Database (gnomAD) using eleven different silico prediction tools. We found that 64 novel were consistently...
Cytochrome P450 oxidoreductase (POR) is an essential redox partner for steroid and drug-metabolizing cytochromes located in the endoplasmic reticulum. Mutations POR lead to metabolic disorders, including congenital adrenal hyperplasia, affect metabolism of steroids, drugs, xenobiotics. In this study, we examined approximately 450 missense variants gene listed Genome Aggregation Database (gnomAD) using eleven different silico prediction tools. We found that 64 novel were consistently...
Abstract Cytochrome P450 oxidoreductase (POR) is the redox partner of steroid and drug-metabolizing cytochromes located in endoplasmic reticulum. Mutations POR cause a broad range metabolic disorders. The variant rs17853284 (P228L) identified by genome sequencing has been linked to lower testosterone levels reduced activities. We expressed wild type P228L bacteria, purified proteins, performed protein stability catalytic functional studies. Variant affected as evidenced unfolding...
Context: Mutations in Cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We are reporting novel R550W mutation POR identified 46, XX patient with signs aromatase deficiency. Objective: Analysis deficiency from POR. Design, Setting, and Patient: Both the child mother had virilization. Ultrasound revealed presence uterus ovaries. No defects CYP19A1 were found, but further analysis targeted Disorders Sexual Development NGS panel (DSDSeq.V1, 111 genes) on...
Rabson-Mendenhall syndrome is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We are reporting the first case of Paraguayan patient. The patient 5-year-old girl who presented with hypertrichosis, acanthosis nigricans, and nephrocalcinosis. Genetic testing NGS revealed two pathogenic variants exons 2 18 INSR gene; c.332G>T (p. Gly111Val) c.3485C>T Ala1162Val), combined heterozygosis. novel c....
Abstract A broad spectrum of human diseases are caused by mutations in the NADPH cytochrome P450 oxidoreductase (POR). Cytochrome proteins perform several reactions, including metabolism steroids, drugs, and other xenobiotics. In 2004 first patients with defects POR were reported, over 250 variations known. Information about effects variants on drug metabolizing enzymes is limited has not received much attention. By analyzing sequences from genomics databases, we identified potentially...
Abstract Cytochromes P450 located in the endoplasmic reticulum require NADPH cytochrome oxidoreductase (POR) for their catalytic activities. Mutations POR cause multiple disorders humans related to biosynthesis of steroid hormones and also affect drug-metabolizing Here we are reporting effects a genetic variant P284T which is hinge region that necessary flexibility domain movements. Human wild-type mutant POR, as well proteins, were expressed bacteria, purified then reconstituted liposomes...
Context: Mutations in Cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We are reporting novel R550W mutation POR identified 46, XX patient with signs aromatase deficiency. Objective: Analysis deficiency from POR. Design, Setting, and Patient: Both the child mother had virilization. Ultrasound revealed presence uterus ovaries. No defects CYP19A1 were found, but further analysis targeted Disorders Sexual Development NGS panel (DSDSeq.V1, 111 genes) on...
Cytochrome P450 oxidoreductase (POR) is the redox partner of steroid and drug-metabolizing cytochromes located in endoplasmic reticulum. Mutations POR cause a broad range metabolic disorders. The variant rs17853284 (P228L) identified by genome sequencing has been linked to lower testosterone levels reduced activities. We expressed wild type P228L bacteria, purified proteins, performed protein stability catalytic functional studies. Variant affected as evidenced unfolding temperatures higher...
<b>Abstract ID 17329</b> <b>Poster Board 584</b> Cytochrome P450 oxidoreductase (POR) is the obligatory redox partner of steroid and drug-metabolizing cytochrome P450s located in endoplasmic reticulum. Mutations POR cause a broad range disorders like congenital adrenal hyperplasia alter metabolism clinically relevant drugs. In this study, we analyzed around 400 missense variants gene indexed Genome Aggregation Database (gnomAD) using eleven different<i> silico</i> prediction tools. We...
A broad spectrum of human diseases, including abnormalities in steroidogenesis, is caused by mutations the NADPH cytochrome P450 oxidoreductase (POR) [1 , 2] . Cytochrome proteins perform several reactions, metabolism steroids, drugs, and other xenobiotics. Therefore, genetic variations POR can impact many different metabolic pathways changing activities cytochromes P450. In 2004 first patients with defects were reported symptoms ambiguous genitalia bone malformations, over 200 are known. By...
Cytochrome P450 oxidoreductase (POR) is the obligatory redox partner of steroid and drug metabolizing cytochrome P450s located in endoplasmic reticulum. Mutations POR cause a broad range disorders like congenital adrenal hyperplasia. Genome sequencing studies have revealed existence missense variant P228L which was linked with reduced function some enzymes. We aimed to expand enzymatic for its role human metabolism. expressed wild type bacteria purified proteins by Affinity Chromatography....