Uridine

Cytidine triphosphate (CTP), as a substance involved in the metabolism of phospholipids, proteins and nucleic acids, has precise drug effects and is a direct precursor for the synthesis of drugs such as citicoline. In this study, we established an in vitro six-enzyme cascade system to generate CTP. To avoid thermodynamic bottlenecks, we employed a circuitous and two-stage reaction strategy. Using cytidine as the key substrate, the final product CTP is obtained via the deamination and uridine phosphorylation pathways, relying on the irreversible reaction of cytidine triphosphate synthase to catalyze the amination of uridine triphosphate...

BACKGROUND AND OBJECTIVE: The prediction of pharmacokinetic parameters for drugs metabolised by cytochrome P450 enzymes has been the subject of active research for many years, while the application of in vitro-in vivo extrapolation (IVIVE) techniques for non-cytochrome P450 enzymes has not been thoroughly evaluated. There is still no established quantitative method for predicting hepatic clearance of drugs metabolised by uridine 5'-diphospho-glucuronosyltransferases (UGTs), not to mention those which undergo hepatic uptake...

INTRODUCTION: CAD (MIM*114010) encodes a large multifunctional protein with the enzymatic activity of the first three enzymes initiating and controlling the de novo pyrimidine biosynthesis pathway. Biallelic pathogenic variants in CAD cause the autosomal recessive developmental and epileptic encephalopathy 50 (MIM #616457) or CAD deficiency presenting with epilepsy, status epilepticus (SE), neurological deterioration and anemia with anisopoikilocytosis. Mortality is around 9% of patients, mainly related to the no use of its specific treatment with uridine...

N-acetylglucosamine (GlcNAc) is an important structural component of the cell wall chitin, N-glycans, glycolipids, and GPI-anchors in eukaryotes. GlcNAc kinase phosphorylates GlcNAc into GlcNAc-6-phosphate, a precursor of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) that serves as a substrate for glycan synthesis. Although GlcNAc kinase is found widely in organisms ranging from microorganisms to mammals, it has never been found in the model yeast Saccharomyces cerevisiae. Here, we demonstrate the presence of GlcNAc metabolism for UDP-GlcNAc biosynthesis in S...

Uridine diphosphate glycosyltransferase(UGT) is involved in the glycosylation of a variety of secondary metabolites in plants and plays an important role in plant growth and development and regulation of secondary metabolism. Based on the genome of a diploid Chrysanthemum indicum, the UGT gene family from Ch. indicum was identified by bioinformatics methods, and the physical and chemical properties, subcellular localization prediction, conserved motif, phylogeny, chromosome location, gene structure, and gene replication events of UGT protein were analyzed...

The Xenopus Eleutheroembryonic Thyroid Assay (XETA) was recently published as an OECD Test Guideline for detecting chemicals acting on the thyroid axis. However, the OECD validation did not cover all mechanisms that can potentially be detected by the XETA. This study was therefore initiated to investigate and consolidate the applicability domain of the XETA regarding the following mechanisms: thyroid hormone receptor (THR) agonism, sodium-iodide symporter (NIS) inhibition, thyroperoxidase (TPO) inhibition, deiodinase (DIO) inhibition, glucocorticoid receptor (GR) agonism, and uridine 5'-diphospho-glucuronosyltransferase (UDPGT) induction...

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0 , we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines...

The silkworm (Bombyx mori) is an important model lepidopteran insect and can be used to identify pesticide resistance-related genes of great significance for biological control of pests. Uridine diphosphate glucosyltransferases (UGTs), found in all organisms, are the main secondary enzymes involved in the metabolism of heterologous substances. However, it remains uncertain if silkworm resistance to fenpropathrin involves UGT. This study observes significant variations in BmUGT expression among B. mori strains with variable fenpropathrin resistance post-feeding, indicating BmUGT's role in fenpropathrin detoxification...

The techniques LC-UV-BPSU and LC-UV-SPE/NMR were applied for the first time in the analysis of açai berry ( Euterpe oleracea Mart.) pulp extracts. Those techniques allowed the identification of twenty-three metabolites: Valine (1), citric acid (2), tachioside (3), isotachioside (4), α -guaiacylglycerol (5), syringylglycerol (6), uridine (7), adenosine (8), dimethoxy-1,4-benzoquinone (9), koaburaside (10), protocatechuic acid (11), eurycorymboside B (12), 7',8'-dihydroxy-dihydrodehydroconiferyl alcohol-9- O - β-D -glucopyranoside (13), orientin (14), homoorientin (15), dihydrokaempferol-3-glucoside (16), isolariciresinol-9'- O-β-D -glucopyranoside (17), 5'-methoxyisolariciresinol-9'- O-β-D -glucopyranoside (18), cyanidin-3- O -glucoside (19), cyandin-3- O -rutenoside (20), 9,12-octadecadienoic acid (Z,Z)-2-hydroxy-1-(hydroxymethyl) ethyl ester (21), linolenic acid (22), and 1,2-di- O - α -linolenoyl-3- O-β-D -galactopyranosyl-sn-glycerol (23)...

Understanding the molecular mechanisms of aging is crucial for enhancing healthy longevity. We conducted untargeted lipidomics across 13 biological samples from mice at various life stages (2, 12, 19 and 24 months) to explore the potential link between aging and lipid metabolism, considering sex (male or female) and microbiome (specific pathogen-free or germ-free) dependencies. By analyzing 2,704 molecules from 109 lipid subclasses, we characterized common and tissue-specific lipidome alterations associated with aging...

The degradation of three anti-cancer drugs (ADs), Capecitabine (CAP), Bicalutamide (BIC) and Irinotecan (IRI), in ultrapure water by ozonation and UV-irradiation was tested in a bench-scale reactor and AD concentrations were measured through ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). A low-pressure mercury UV (LP-UV) lamp was used and degradation by UV (λ = 254 nm) followed pseudo-first order kinetics. Incident radiation in the reactor was measured via chemical actinometry using uridine...

Finding potent inhibitors of O-GlcNAc transferase (OGT) has proven to be a challenge, especially because the diversity of published inhibitors is low. The large majority of available OGT inhibitors are uridine-based or uridine-like compounds that mimic the main interactions of glycosyl donor UDP-GlcNAc with the enzyme. Until recently, screening of DNA-encoded libraries for discovering hits against protein targets was dedicated to a few laboratories around the world, but has become accessible to wider public with the recent launch of the DELopen platform...

The AID/APOBECs are a group of zinc-dependent cytidine deaminases that catalyse the deamination of bases in nucleic acids, resulting in a cytidine to uridine transition. Secreted novel AID/APOBEC-like deaminases (SNADs), characterized by the presence of a signal peptide are unique among all of intracellular classical AID/APOBECs, which are the central part of antibody diversity and antiviral defense. To date, there is no available knowledge on SNADs including protein characterization, biochemical characteristics and catalytic activity...

Previous work demonstrated that human liver microsomes (HLM) can spontaneously bind to silica-coated magnetizable beads (HLM-beads) and that these HLM-beads retain UGT activity. However, the contributions of individual UGT isoforms is not directly assessable in this system except through use of model inhibitors. Thus, a preparation wherein rUGT microsomes bound to these same beads to form rUGT-beads of individual UGT isoforms would provide a novel system for measuring the contribution of individual UGT isoforms in a direct manner...

Molnupiravir is an oral prodrug of the broadly active, antiviral ribonucleoside analog N-hydroxycytidine (NHC). The primary circulating metabolite NHC is taken up into cells and phosphorylated to NHC-triphosphate (NHC-TP). NHC-TP serves as a competitive substrate for viral RNA-dependent RNA polymerase (RdRp), which results in an accumulation of errors in the viral genome, rendering virus replication incompetent. Molnupiravir has demonstrated activity against SARS-CoV-2 both clinically and preclinically and has a high barrier to development of viral resistance...

RNA interference (RNAi)-based gene silencing is a feasible and sustainable technology for the management of hemipteran pests by double-stranded RNA involvement, including small-interfering RNA, microRNA, and Piwi-interacting RNA (piRNA) pathways, that may help to decrease the usage of chemical insecticides. However, only a few data are available on the somatic piRNAs and their biogenesis genes in Riptortus pedestris, which serves as a significant pest of soybean (Glycine max). In this study, two family members of the PIWI gene were identified and characterized in R...

This study accessed the potential antimalarial activity of triterpene glycoside of H. atra through targeting orotidine 5-monophosphate decarboxylase protein (PfOMPDC) in P. falciparum by molecular docking. Nine triterpene glycosides from H. atra extract modeled the structure by the Corina web server and interacted with PfOMPDC protein by using Hex 8.0.0. The docking results were visualized and analyzed by Discovery Studio version 21.1.1. 17-Hydroxyfuscocineroside B showed the lowest binding energy in PfOMPDC interaction, which was -1,098...

RNA editing is a crucial modification in plants' organellar transcripts that converts cytidine to uridine (C-to-U; and sometimes uridine to cytidine) in RNA molecules. This post-transcriptional process is controlled by the PLS-class protein with a DYW domain, which belongs to the pentatricopeptide repeat (PPR) protein family. RNA editing is widespread in land plants; however, complex thalloid liverworts (Marchantiopsida) are the only group reported to lack both RNA editing and DYW-PPR protein. The liverwort Cyathodium cavernarum (Marchantiopsida, Cyathodiaceae), typically found in cave habitats, was newly found to have 129 C-to-U RNA editing sites in its chloroplast and 172 sites in its mitochondria...

Lafora disease is a fatal teenage-onset progressive myoclonus epilepsy and neurodegenerative disease associated with polyglucosan bodies. Polyglucosans are long-branched and as a result precipitation- and aggregation-prone glycogen. In mouse models, downregulation of glycogen synthase, the enzyme that elongates glycogen branches, prevents polyglucosan formation and rescues Lafora disease. Mouse work, however, has not yet revealed the mechanisms of polyglucosan generation, and few in vivo human studies have been performed...

LC-MS is an indispensable tool for small molecule analysis in many fields; however, many small molecules require chemical derivatization to improve retention on commonly used reversed-phase columns and increase ionization. Benzoyl chloride (BzCl) derivatization is commonly used for derivatization of primary and secondary amines and phenolic alcohols, though evidence exists that with proper reaction conditions (i.e., specific bases), other hydroxyl groups may be derivatized too. Previous studies have examined BzCl concentration, reaction times, and reaction temperatures for derivatization of amines and phenols for LC-MS analysis; however, use of different bases, base concentration, and extending to conditions to hydroxyl groups for LC-MS analysis has not been well-studied...