A5082980806- Metabolism and Genetic Disorders
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- Diet and metabolism studies
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Folate and B Vitamins Research
- Photosynthetic Processes and Mechanisms
- Glycosylation and Glycoproteins Research
- Amino Acid Enzymes and Metabolism
- Enzyme Structure and Function
- Retinoids in leukemia and cellular processes
- Epigenetics and DNA Methylation
- Biotin and Related Studies
- Neurological diseases and metabolism
- Byzantine Studies and History
- Microbial Metabolic Engineering and Bioproduction
- Ion channel regulation and function
- Calcium signaling and nucleotide metabolism
- Genetics, Aging, and Longevity in Model Organisms
- Neurobiology and Insect Physiology Research
- Cancer Research and Treatments
- Dendrimers and Hyperbranched Polymers
- Cancer, Lipids, and Metabolism
University of Bari Aldo Moro
2015-2025
University of Calabria
2019
Office of Infectious Diseases
1988
Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and neuromuscular phenotype. Despite recent advances in understanding the genetic basis MADD, number cases remain unexplained. Here, we report clinically relevant variants FLAD1, which encodes FAD synthase (FADS), as cause MADD dysfunction nine individuals recruited from centers six countries. In most individuals, identified biallelic frameshift...
The mechanisms regulating activation of the respiratory burst enzyme, NADPH oxidase, human neutrophils (PMN) are not yet understood, but protein phosphorylation may play a role. We have utilized defect in cytosolic factor required for oxidase observed two patients with autosomal recessive form chronic granulomatous disease (CGD) to examine role cell-free system. could be activated by SDS reconstitution mixtures and membrane subcellular fractions from normal PMN, also enhanced at least 16 14...
The primary role of the water-soluble vitamin B2 (riboflavin) in cell biology is connected with its conversion into FMN and FAD, cofactors a large number dehydrogenases, oxidases reductases involved broad spectrum biological activities, among which energetic metabolism chromatin remodeling. Subcellular localisation FAD synthase (EC 2.7.7.2, FADS), second enzyme forming pathway, addressed here HepG2 cells by confocal microscopy, frame relationships kinetics synthesis delivery to client...
Human flavin adenine dinucleotide synthase (hFADS) is a bifunctional, multi-domain enzyme that exhibits both mononucleotide adenylyltransferase and pyrophosphatase activities. Here we report the crystal structure of full-length hFADS2 its C-terminal PAPS domain in complex with (FAD), dissect structural determinants underlying contribution each individual domain, within isoforms 1 2, to two enzymatic Structural functional characterization performed on complete or truncated constructs...
FAD synthase (FADS, EC 2.7.7.2) is the last essential enzyme involved in pathway of biosynthesis Flavin cofactors starting from Riboflavin (Rf). Alternative splicing human FLAD1 gene generates different isoforms synthase. Besides well characterized isoform 1 and 2, other FADS with catalytic domains have been detected, which are splice variants. We report characterization one these novel isoforms, a 320 amino acid protein, consisting sole C-terminal 3′-phosphoadenosine 5′-phosphosulfate...
In this report, we describe the case of an 11-year-old boy, who came to our attention for myalgia and muscle weakness, associated with inappetence vomiting. Hypertransaminasemia was also noted, ultrasound evidence hepatomegaly. Biochemical investigations revealed acylcarnitine organic acid profiles resembling those seen in MADD, that is, multiple acyl-CoA dehydrogenase deficiencies (OMIM #231680) a rare inherited disorder fatty acids, amino choline metabolism. The patient carried single...
FLAD1, along with its FAD synthase (FADS, EC 2.7.7.2) product, is crucial for flavin homeostasis and, due to role in the mitochondrial respiratory chain and nuclear epigenetics, closely related cellular metabolism. Therefore, it not surprising that could be correlated cancer. To our knowledge, no previous study has investigated FLAD1 prognostic significance pancreatic ductal adenocarcinoma (PDAC). Thus, present work, synthesis process was evaluated two PDAC cell lines: (a) PANC-1-...
FAD synthase (FADS, or FMN:ATP adenylyl transferase) coded by the FLAD1 gene is last enzyme in pathway of synthesis. The mitochondrial isoform 1 and cytosolic 2 are characterized following two domains: C-terminal PAPS domain (FADSy) performing synthesis pyrophosphorolysis; N-terminal molybdopterin-binding (FADHy) a Co++/K+-dependent hydrolysis. Mutations responsible for riboflavin responsive non-responsive multiple acyl-CoA dehydrogenases combined respiratory chain deficiency. In patients...
Abstract Riboflavin (Rf), or vitamin B2, is the precursor of FMN and FAD, redox cofactors several dehydrogenases involved in energy metabolism, balance other cell regulatory processes. FAD synthase, coded by FLAD1 gene humans, last enzyme pathway converting Rf into FAD. Mutations are responsible for neuromuscular disorders, some cases treatable with Rf. In order to mimic these Caenorhabditis elegans ( C. ) orthologue flad‐1 was silenced a model strain hypersensitive RNA interference nervous...
Flavin adenine dinucleotide (FAD) synthase (EC 2.7.7.2), encoded by human flavin synthetase 1 (FLAD1), catalyzes the last step of pathway converting riboflavin (Rf) into FAD. FLAD1 variations were identified as a cause LSMFLAD (lipid storage myopathy due to FAD deficiency, OMIM #255100), resembling Multiple Acyl-CoA Dehydrogenase Deficiency, sometimes treatable with high doses Rf; no alternative therapeutic strategies are available. We describe here cell morphological and mitochondrial...
FAD synthase is the last enzyme in pathway that converts riboflavin into FAD. In Saccharomyces cerevisiae, gene encoding for FAD1, from which a sole protein product (Fad1p) expected to be generated. this work, we showed natural Fad1p exists yeast mitochondria and that, its recombinant form, able, per se, both enter destined cytosol. Thus, propose FAD1 generates two echoforms—that is, identical proteins addressed different subcellular compartments. To shed light on mechanism underlying...