It catalyzes the oxidation of L-gulono-1,4-lactone to L-xylo-hex-3-ulonolactone. (lookformedical.com)
Enzyme3
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)
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)
Dau, H. (2015) Water oxidation by amorphous cobalt-based oxides: in situ tracking of redox transitions and mode of catalysis. (fu-berlin.de)
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)
Microbial3
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)
Microbial ammonia oxidation is vital to the nitrogen cycle. (bvsalud.org)
Microbial flavohemoglobins (flavoHbs) and hemoglobins (Hbs) show large radical dotNO dioxygenation rate constants ranging from 745 to 2900 μM−1 s−1 suggesting a primal radical dotNO dioxygenase (NOD) (EC 1.14.12.17) function for the ancient Hb superfamily. (pharmaceuticalintelligence.com)
Metabolic pathways1
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)
Metabolism2
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)
Nitric1
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)
Substrate5
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)
This Fe=O center then oxygenates the substrate by an oxygen rebound mechanism. (wikipedia.org)
Some αKG-dependent dioxygenases bind their substrate through an induced fit mechanism. (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)
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)
Compounds4
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)
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)
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)
Mechanism1
The mechanism of water oxidation: from electrolysis via homogeneous to biological catalysis. (fu-berlin.de)
Oxygen atom1
αKG-dependent dioxygenases catalyse oxidation reactions by incorporating a single oxygen atom from molecular oxygen (O2) into their substrates. (wikipedia.org)
Antioxidant1
It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. (lookformedical.com)
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)
Inhibitors2
Given the important biological roles that αKG-dependent dioxygenase play, many αKG-dependent dioxygenase inhibitors were developed. (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)
Hydrogen1
Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. (lookformedical.com)
Synthetic1
Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. (lookformedical.com)
Copper1
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)
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)
Role1
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)
Conversion2
This conversion is coupled with the oxidation of the cosubstrate αKG into succinate and carbon dioxide. (wikipedia.org)
Principles, efficiency, and blueprint character of solar-energy conversion in photosynthetic water oxidation. (fu-berlin.de)
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)
Direct2
Thus, although NOX orthologs have been identified in organisms as diverse as plants, fruit flies, rodents, and humans, ROS functions have developed and diversified to affect a multitude of cellular properties, i.e., far beyond direct antimicrobial activity. (frontiersin.org)
A biological process, called Dirammox (direct ammonia oxidation, NH3 â NH2 OHâ N2 ), has been recently identified in Alcaligenes ammonioxydans and Alcaligenes faecalis. (bvsalud.org)
Exhibit2
A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. (lookformedical.com)
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)
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)
Shown2
c) They perform oxidation of metabolite uti-lizing several components of a respiratory chain (shown in Fig. 12.5). (biologydiscussion.com)
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)
Focus1
X-ray absorption spectroscopy to analyze nuclear geometry and electronic structure of biological metal centers-potential and questions examined with special focus on the tetra-nuclear manganese complex of oxygenic photosynthesis. (fu-berlin.de)
Blood3
The S2 thesis is introduced by an ADAM activity activated TACE( TNF glutamine signaling blood). (evakoch.com)
Indeed, modern O2-transporting and storing mammalian red blood cell Hb and related muscle myoglobin (Mb) show vestigial radical dotNO dioxygenation activity with rate constants of 34-89 μM−1 s−1. (pharmaceuticalintelligence.com)
Red blood cell Hb, myocyte Mb, and flavoHb-like activities metabolize radical dotNO in the vascular lumen, muscle, and other mammalian cells, respectively, decreasing radical dotNO signalling and toxicity. (pharmaceuticalintelligence.com)