CatalyseInhibitorsInhibitionMetabolismSubstrateCatalyzesAntioxidantOxidativeBiosynthesisCytochromeSulfhydrylTissuesReactionsPeroxidaseIsoformMetaboliteCompoundsRedoxCollagenConvertsAssaysVitroPancreaticConcentrationCompoundCopperFoundSpectrumRapidlyDescriptionTargetIronExhibitConversionGroupsFamilyEffectsGenerationShownRemovalCellGroupFreeProductBlood
Catalyse4
- Many αKG-dependent dioxygenase also catalyse uncoupled turnover, in which oxidative decarboxylation of αKG into succinate and carbon dioxide proceeds in the absence of substrate. (wikipedia.org)
- αKG-dependent dioxygenases catalyse oxidation reactions by incorporating a single oxygen atom from molecular oxygen (O2) into their substrates. (wikipedia.org)
- a) Enzymes that catalyse the removal of hy-drogen from a substrate but use only oxy-gen as a hydrogen acceptor to form water as a reaction product (with the exception of uricase and monoamine oxidase which form H 2 O 2 ). (biologydiscussion.com)
- Heterologous expression in Nicotiana benthamiana and yeast showed that one of these, CYP712G1, can catalyse the double oxidation of orobanchol, resulting in the formation of three didehydro-orobanchol (DDH) isomers. (bvsalud.org)
Inhibitors9
- The binding of the ketoglutarate has been observed using enzyme inhibitors. (wikipedia.org)
- Given the important biological roles that αKG-dependent dioxygenase play, many αKG-dependent dioxygenase inhibitors were developed. (wikipedia.org)
- The inhibitors that were regularly used to target αKG-dependent dioxygenase include N-oxalylglycine (NOG), pyridine-2,4-dicarboxylic acid (2,4-PDCA), 5-carboxy-8-hydroxyquinoline, FG-2216 and FG-4592, which were all designed mimic the co-substrate αKG and compete against the binding of αKG at the enzyme active site Fe(II). (wikipedia.org)
- Although they are potent inhibitors of αKG-dependent dioxygenase, they lack selectivity and hence sometimes being referred to as so-called 'broad spectrum' inhibitors. (wikipedia.org)
- Inhibitors that compete against the substrate were also developed, such as peptidyl-based inhibitors that target human prolyl hydroxylase domain 2 (PHD2) and Mildronate, a drug molecule that is commonly used in Russia and Eastern Europe that target gamma-butyrobetaine dioxygenase. (wikipedia.org)
- Finally, as αKG-dependent dioxygenases require molecular oxygen as a co-substrate, it has also been shown that gaseous molecules such as carbon monoxide and nitric oxide are inhibitors of αKG-dependent dioxygenases, presumably by competing with molecular oxygen for the binding at the active site Fe(II) ion. (wikipedia.org)
- Herein, we also demonstrate that compounds developed to target mutant IDH1 can be repurposed as wild-type IDH1 inhibitors, because these drugs surprisingly become potent inhibitors of wtIDH1 in cancer cells under conditions present in tumors: specifically, we found that wtIDH1 is critical for PDAC cell survival under low-glucose conditions, and allosteric IDH inhibitors effectively block wtIDH1 activity under low magnesium. (nature.com)
- In vitro production of enzymatically active O. volvulus prolyl 4-hydroxylase should facilitate identification of specific inhibitors of the parasite enzyme. (embl.de)
- Because a decreased dependence on aerobic respiration becomes advantageous, cell metabolism is shifted toward glycolysis by the increased expression of glycolytic enzymes, glucose transporters, and inhibitors of mitochondrial metabolism. (pharmaceuticalintelligence.com)
Inhibition1
- Many assays were developed to study αKG-dependent dioxygenases so that information such as enzyme kinetics, enzyme inhibition and ligand binding can be obtained. (wikipedia.org)
Metabolism4
- In plants, αKG-dependent dioxygenases are involved in diverse reactions in plant metabolism. (wikipedia.org)
- In mammals and humans, αKG-dependent dioxygenase have functional roles in biosyntheses (e.g. collagen biosynthesis and L-carnitine biosynthesis), post-translational modifications (e.g. protein hydroxylation), epigenetic regulations (e.g. histone and DNA demethylation), as well as sensors of energy metabolism. (wikipedia.org)
- In this review, we introduce mass spectrometry-based analytical methods contributing to recent discovery of various metabolic pathways regulating ferroptosis, focusing on cysteine metabolism, antioxidant metabolism, and poly-unsaturated fatty acid metabolism. (bmbreports.org)
- An enzyme involved in the metabolism of ASCORBIC ACID and aldarate. (lookformedical.com)
Substrate3
- Some αKG-dependent dioxygenases bind their substrate through an induced fit mechanism. (wikipedia.org)
- For example, significant protein structural changes have been observed upon substrate binding for human prolyl hydroxylase isoform 2 (PHD2), a αKG-dependent dioxygenase that is involved in oxygen sensing, and isopenicillin N synthase (IPNS), a microbial αKG-dependent dioxygenase. (wikipedia.org)
- b) They transfer hydrogen from one substrate to another by oxidation-reduction reac-tion not involving a respiratory chain (shown in Fig. 12.4. (biologydiscussion.com)
Catalyzes3
- b) It catalyzes the oxidation of uric acid to allantoin. (biologydiscussion.com)
- IDH1 is a cytosolic enzyme that catalyzes the reversible conversion of isocitrate and αKG. (nature.com)
- It catalyzes the oxidation of L-gulono-1,4-lactone to L-xylo-hex-3-ulonolactone. (lookformedical.com)
Antioxidant3
- Out of 40 antioxidant enzymes, only IDH1 expression was lost in multiple HuR-knockout cell lines, pointing to an HuR- IDH1 regulatory axis as a key component of the acute antioxidant response to stress 2 , 24 . (nature.com)
- By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS. (lookformedical.com)
- It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. (lookformedical.com)
Oxidative1
- The following points highlight the five main enzymes involved in oxidative process. (biologydiscussion.com)
Biosynthesis1
- The enzyme responsible for collagen maturation is prolyl 4-hydroxylase, making this enzyme a central activity in cuticle biosynthesis and a potentially important chemotherapeutic target. (embl.de)
Cytochrome1
- Functionally, the αKG-dependent hydroxylases are comparable to cytochrome P450 enzymes. (wikipedia.org)
Sulfhydryl2
- Modern mass spectrometry based analytical techniques play a crucial role in the discovery of metabolic alteration regulating ferroptosis by extensive analysis of metabolites such as the sulfhydryl residue containing cysteine metabolites, RTAs, and membrane phospholipids. (bmbreports.org)
- Alternative sites for cell density regulation of the enzyme could rely on its sensitivity to sulfhydryl groups. (embl.de)
Tissues2
- They counteract the harmful and damaging effects of oxidation in animal tissues. (lookformedical.com)
- Another exciting discovery is that of the 'sixth base' in DNA i.e. hydroxylation of methylated cytosines (5mC) by enzymes leading to '5hmC' that is present in many tissues. (stanford.edu)
Reactions1
- Although polypharmacology might be associated with compound promiscuity, it should be considered a different category since the so-called promiscuous drugs are instead a class of compound that show a wide spectrum of biological activities and adverse reactions [ 1 ]. (biomedcentral.com)
Peroxidase1
- Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. (lookformedical.com)
Isoform1
- The derived amino acid sequence of Ov-phy-1 encoded a peptide that was most similar to the two Caenorhabditis elegans prolyl 4-hydroxylase homologues and to the isoform II enzymes of vertebrates. (embl.de)
Metabolite1
- c) They perform oxidation of metabolite uti-lizing several components of a respiratory chain (shown in Fig. 12.5). (biologydiscussion.com)
Compounds2
- Deficiency of pantothenate kinase may lead to accumulation of cysteine and cysteine-containing compounds in the basal ganglia. (medscape.com)
- MCE owns a unique collection of 17212 compounds with confirmed biological activities and clear targets. (chemscene.com)
Redox2
- In addition, distinct NOX homologs expressed by non-phagocytic cells and mitochondrial ROS are interlinked with phagocytic NOX functions and thus affect the overall redox state of the tissue and the cellular activity in a complex fashion. (frontiersin.org)
- Oxidized cysteine residues are highly reactive and can form functional covalent conjugates, of which the allosteric redox switch formed by the lysine-cysteine NOS bridge is an example. (hokudai.ac.jp)
Collagen1
- Earlier reports indicated that underhydroxylated collagen, accumulating within the endoplasmic reticulum in cells where prolyl 4-hydroxylase is inactivated, is slowly degraded, but is then rapidly hydroxylated and secreted when the activity of prolyl 4-hydroxylase is restored. (embl.de)
Converts1
- An enzyme that converts ascorbic acid to dehydroascorbic acid. (lookformedical.com)
Assays2
- Hatching assays with PCN, Globodera pallida, with root exudates of tomato genotypes revealed a significant positive correlation between SolA concentration and hatching activity. (bvsalud.org)
- This protein has E3 ubiquitin ligase activity based on in vitro assays. (or.jp)
Vitro2
- To benefit from those effects, it is required that the multitarget drug exhibit balanced in vitro and in vivo activities to match potency for the corresponding targets, as well as optimized PK and safety profiles. (biomedcentral.com)
- in vitro activity of anidulafungin. (liverpool.ac.uk)
Pancreatic2
- In pancreatic cancer cells a cytosolic metabolic enzyme, wild-type isocitrate dehydrogenase 1 (wtIDH1), enables adaptation to these conditions. (nature.com)
- Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries. (lookformedical.com)
Concentration1
- Its low concentration in potato root exudate has hindered progress in fully understanding its hatching inducing activity and exploitation in the control of PCN. (bvsalud.org)
Compound1
- Our ready-to-use ChemScene compound libraries consist of over 4000 small molecules with validated biological and pharmacological activities. (chemscene.com)
Copper3
- g) This enzyme system contains copper, a component of several oxidase enzymes. (biologydiscussion.com)
- a) It is a copper-containing enzyme. (biologydiscussion.com)
- Osei P, Northcote-Smith J, Fang J, Singh K, Ortu F, Suntharalingam K . The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Bi-nuclear Copper(II)-Phenanthroline Complexes. (le.ac.uk)
Found1
- A similar facial Fe-binding motif, but featuring his-his-his array, is found in cysteine dioxygenase. (wikipedia.org)
Spectrum1
- the spectrum of activity of anidulafungin includes candida and aspergillus, the two main etiological agents causing invasive fungal infections. (liverpool.ac.uk)
Rapidly1
- Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. (biomedcentral.com)
Description2
- Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Malate Dehydrogenase 1 (MDH1) in tissue homogenates, cell lysates, cell culture supernates and other biological fluids. (operatiebrp.nl)
- Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Rat Malate Dehydrogenase 1 (MDH1) in samples from tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species. (operatiebrp.nl)
Target1
- Based on our previous studies revealing IDH1 as a regulatory target of HuR, and the enzyme's direct role in the generation of NADPH and αKG through the oxidation of isocitrate, we hypothesized that wtIDH1 is essential for PDAC cells under metabolic stress. (nature.com)
Iron3
- One proposed hypothesis is that abnormal peroxidation of lipofuscin to neuromelanin and deficient cysteine dioxygenase lead to abnormal iron accumulation in the brain. (medscape.com)
- [ 11 ] This was postulated to lead to accumulation of cysteine in the basal ganglia, since cysteine can chelate iron and thus result in its deposition. (medscape.com)
- This causes chelation of iron in the globus pallidus and free radical generation as a result of rapid auto-oxidation of cysteine in the presence of iron. (medscape.com)
Exhibit1
- A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. (lookformedical.com)
Conversion1
- This conversion is coupled with the oxidation of the cosubstrate αKG into succinate and carbon dioxide. (wikipedia.org)
Groups1
- c) They are flavoprotein enzymes having FMN (flavin mononucleotide) or FAD (Flavin adenine dinucleotide) as pros-thetic groups. (biologydiscussion.com)
Family1
- ions are as composed in the caveolin of triple integrin factor through FAK which is the SLC27 family to fat effect CSNK1E and offer non deformed activity complex( Shi et al. (familie-vos.de)
Effects1
- download Dopamine in the Pathophysiology and Treatment involves a histone of endonucleases, receptor effects catalyzed in solar enzymes. (evakoch.com)
Generation1
- This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed. (biomedcentral.com)
Shown1
- For a glioblastoma, the tumor microenvironment has been shown to have increased activity of natural immune checkpoints, which as their name implies, helps prevent an overzealous immune response that could hurt the body, like what happens in autoimmune diseases like rheumatoid arthritis. (regenerativemedicine.net)
Removal1
- DNA demethylation has received scant attention over the years mainly due to the inability to identify enzymes that could mediate the removal of the methylation marks. (stanford.edu)
Cell1
- Cell density regulates prolyl 4-hydroxylase activity independent of mRNA levels. (embl.de)
Group1
- Here, we report a noncanonical FAD-dependent enzyme Orf1 that adds a glycine-derived N-formimidoyl group to glycinothricin to form the antibiotic BD-12. (hokudai.ac.jp)
Free1
- Moreover, an intermediate-enzyme adduct with a NOS-covalent linkage was observed in the later site, where it acts as a two-scissile-bond linkage facilitating nucleophilic addition and cofactor-free decarboxylation. (hokudai.ac.jp)
Product1
- The resultant product is no longer sensitive to aminoglycoside-modifying enzymes, a strategy that antibiotic-producing species employ to counter drug resistance in competing species. (hokudai.ac.jp)
Blood1
- The S2 thesis is introduced by an ADAM activity activated TACE( TNF glutamine signaling blood). (evakoch.com)