Human UDP-Glucuronosyltransferase (UGT) 2B10 in Drug N-Glucuronidation: Substrate Screening and Comparison with UGT1A3 and UGT1A4Human UDP-Glucuronosyltransferase (UGT) 2B10 in Drug N-Glucuronidation: Substrate Screening and Comparison with UGT1A3 and UGT1A4 ...
A cDNA clone, designated UGT2B7 variant, encoding a 529-amino acid human liver microsomal uridine diphosphate-glucuronosyltransferase (UGT) was isolated from a lambda gt11 human liver cDNA library. UGT2B7 variant synthesized in COS-7 cells was screened for activity toward a range of clinically used drugs and other xenobiotics. The expressed enzyme glucuronidated several carboxylic acid-containing nonsteroidal antiinflammatory agents including, in order of relative substrate activity, naproxen, ketoprofen, ibuprofen, fenoprofen, tiaprofenic acid, benoxprofen, zomepirac, diflunisal and indomethacin. Additionally, the stereoselectivity of ketoprofen, naproxen (S/R ratio approximately unity) and ibuprofen (S/R ratio 1.62) glucuronidation by the UGT2B7 variant was shown to differ. Two other carboxylic acid-containing drugs (clofibric acid and valproic acid) and a limited range of drugs containing an alcohol or phenolic functional group were also glucoronidated by expressed UGT2B7 variant. The deduced ...
K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17] K00699 UGT; glucuronosyltransferase [EC:2.4.1.17 ...
Sigma-Aldrich offers abstracts and full-text articles by [Yan-Qing Liu, Ling-Min Yuan, Zhang-Zhao Gao, Yong-Sheng Xiao, Hong-Ying Sun, Lu-Shan Yu, Su Zeng].
in vitro study results indicate that pasireotide is not a substrate, inhibitor, or inducer for metabolic isozymes including UGT1A1 particularly at the proposed dosing range. ...
Glucuronidation of thyroxine is a major metabolic pathway facilitating its excretion. In this study, we characterized the glucuronidation of thyroxine in human liver, jejunum, and kidney microsomes, and identified human UDP-glucuronosyltransferase (UGT) isoforms involved in the activity. Human jejunum microsomes showed a lower Km value (24.2 μM) than human liver (85.9 μM) and kidney (53.3 μM) microsomes did. Human kidney microsomes showed a lower Vmax value (22.6 pmol/min/mg) than human liver (133.4 pmol/min/mg) and jejunum (184.6 pmol/min/mg) microsomes did. By scaling-up, the in vivo clearances in liver, intestine, and kidney were estimated to be 1440, 702, and 79 μl/min/kg body weight, respectively. Recombinant human UGT1A8 (108.7 pmol/min/unit), UGT1A3 (91.6 pmol/min/unit), and UGT1A10 (47.3 pmol/min/unit) showed high, and UGT1A1 (26.0 pmol/min/unit) showed moderate thyroxine glucuronosyltransferase activity. The thyroxine glucuronosyltransferase activity in microsomes from 12 human ...
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The protein encoded by this gene belongs to the UDP-glycosyltransferase family, members of which catalyze biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. This gene shares exon structure with the UDP glucuronosyltransferase 2A2 family member, which encodes N-terminally distinct isoforms. [provided by RefSeq, Jul 2014]
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Authors Affiliations: 1Channing Laboratory, Department of Medicine, Brigham and Womens Hospital and Harvard Medical School; Departments of 2Epidemiology, 3Biostatistics, 4Medicine, Boston University School of Medicine, Boston, Massachusetts; 5Institute of Pathology, 6Department of Clinical Epidemiology, 7Department of Surgery, Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark; 8Department of Surgery, Stavanger University Hospital, Stavanger, Norway; and 9Hormone Laboratory, Haukeland University Hospital, Bergen, ...
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Bovine serum albumin (BSA) and fatty acid-free human serum albumin (HSAFAF) reduce the Km values for UGT2B7 substrates by sequestering inhibitory long-chain fatty acids released by incubations of human liver microsomes (HLM) and HEK293 cells expressing this enzyme. However, the scope of the "albumin effect" is unknown. In this investigation we characterized the effects of albumin on the kinetics of 4-methylumbelliferone (4MU) glucuronidation by UDP-glucuronosyltransferase (UGT) 1A1, 1A6, and 1A9, and propofol (PRO) glucuronidation by UGT1A9 and HLM. BSA and HSAFAF, but not human serum albumin, reduced the Km values for 4MU and PRO glucuronidation by UGT1A9. For example, HSAFAF (2%) reduced the Km values for 4MU and PRO glucuronidation from 13.4 to 2.9 and 41 to 7.2 μM, respectively. Similarly, HSAFAF (2%) reduced the Km for PRO glucuronidation by HLM from 127 to 10.6 μM. Arachidonic, linoleic, and oleic acids and a mixture of these decreased the rates of 4MU and PRO glucuronidation by UGT1A9. ...
Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450) and uridine diphosphate glucuronosyltransferase (UGT) enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide). The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed.
Uridine 5-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) is a cytosolic glycosyltransferase (EC 2.4.1.17) that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is a glucuronidation reaction. Alternative names: glucuronyltransferase UDP-glucuronyl transferase UDP-GT Glucuronosyltransferases are responsible for the process of glucuronidation, a major part of phase II metabolism. Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s. The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human bodys elimination of the most frequently prescribed drugs. It is also the major pathway for foreign chemical (dietary, environmental, pharmaceutical) removal for most drugs, dietary substances, toxins and endogenous substances. ...
The ATP-binding cassette transporters P-glycoprotein (ABCB1 MDR1) and multidrug resistance protein 4 (MRP4) efflux irinotecan and its active metabolite SN-38 genotype was a significant covariate for the clearance of both irinotecan Epigallocatechin gallate lactone and SN-38 Epigallocatechin gallate lactone. of the topoisomerase Epigallocatechin gallate I enzyme [2]. SN-38 undergoes glucuronic acid Rabbit polyclonal to TranscriptionfactorSp1. conjugation to form SN-38 glucuronide by uridine diphosphate glucuronosyltransferase. A diagram of Epigallocatechin gallate irinotecan metabolic pathways has been recently published {Innocenti 2009.. ...
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; Al = aluminum; ARV = antiretroviral; ATV = atazanavir; BIC = bictegravir; Ca = calcium; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; Fe = iron; FPV = fosamprenavir; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; MATE = multidrug and toxin extrusion transporter; Mg = magnesium; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitors; NRTI = nucleoside reverse transcriptase inhibitors; NVP = nevirapine; OCT2 = organic cation transporter 2; OATP = organic anion-transporting polypeptide; PK = pharmacokinetic; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; T-20 = enfuvirtide; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; UGT = uridine diphosphate glucuronosyltransferase; ZDV = zidovudine; Zn = zinc ...
I start abusing my meds to a dangerous point because I just want to feel anything than what I am feeling then. This oral medication has gabapentin and nuvaring a lot of popularity due to its distinguishing ability to provide respite from the devastating health symptoms in a quick span of time. Availability Rx Prescription only. Hows everybody combating their monthly issues? Increased metabolism of lamotrigine by OC induction of the uridine diphosphate glucuronosyltransferase system has been demonstrated as the likely mechanism. Oral contraceptives reduce lamotrigine plasma levels. When it is used at higher doses for colonoscopy prep, it can cause gabapentin and nuvaring form of kidney damage and kidney failure known as acute phosphate nephropathy.. Ketek anr is an antibiotic used to treat bacteria infections that are found in the lungs, sinus, and throat. Luef G, Abraham I, Haslinger M, et al. Abilify Acyclovir Adderall Alprazolam Amlodipine Androgel Bactrim Botox Chantix Cialis Cipro Cymbalta ...
UDP glucuronosyltransferase 1 family, polypeptide A cluster, also known as [email protected], is a human gene. This RefSeq represents a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5 exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. "Human PubMed Reference:". "Entrez Gene: [email protected] UDP glucuronosyltransferase 1 family, polypeptide A cluster". Mackenzie PI, Owens IS, Burchell B, et al. (1997). "The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence". Pharmacogenetics. 7 (4): 255-69. doi:10.1097/00008571-199708000-00001. PMID 9295054. Tukey RH, Strassburg CP (2000). "Human ...
Compiled By Jessica Oesterheld, M.D. This table is an abridged guide to UGTs. To appreciate the full benefits of this information, click here to get a free 30-day trial version of GeneMedRx. This metabolism-based drug interaction software predicts response to medication combinations with optional input of genetic variations.. Last Update: May 16, 2008 ...
TY - JOUR. T1 - Differential glucuronidation of bile acids, androgens and estrogens by human UGT1A3 and 2B7. AU - Gall, Walter E.. AU - Zawada, Gregory. AU - Mojarrabi, Behnaz. AU - Tephly, Thomas R.. AU - Green, Mitchell D.. AU - Coffman, Birgit L.. AU - Mackenzie, Peter I.. AU - Radominska-Pandya, Anna. PY - 1999/7. Y1 - 1999/7. N2 - In this work, UDP-glucuronosyltransferases (UGTs), UGT1A3, 2B7(H268) and 2B7(Y268), stably expressed in human embryonic kidney cells (HK293) were used to assess glucuronidation activities with a variety of steroid hormone and bile acid substrates. The rate of synthesis of carboxyl- and hydroxyl-linked glucuronides was determined under optimal reaction conditions. Expressed UGT1A3 catalyzed bile acid glucuronidation at high rates exclusively at the carboxyl moiety for all compounds tested. In contrast, UGT1A4 catalyzed bile acid glucuronidation at very low rates exclusively at the 3α-hydroxyl function. Both UGT2B7 allelic variants glucuronidated the bile acid ...
Genetic (structural) polymorphisms of human drug-metabolizing enzymes, including cytochrome P-450, glutathione-S-transferases, andN-acetyltransferases, have been identified and evaluated as determinants underlying interindividual differences in drug metabolism and potential adverse drug reactions (Daly, 1995; Meyer and Zanger, 1997). For some of the UGT genes, such as UGT1A1,UGT1A6, UGT2B4, UGT2B7, andUGT2B15, polymorphic alleles have also been identified (Ciotti et al., 1997; Levesque et al., 1997; Coffman et al., 1998;Lampe et al., 1999; Levesque et al., 1999). For UGT1A1, which is the only UGT isoform capable of biologically relevant bilirubin glucuronidation (Bosma et al., 1994), as many as 32 allelic variants have been identified (for review, see Tukey and Strassburg, 2000). Many groups have studied these genetic polymorphisms because they form the genetic basis for hereditary unconjugated hyperbilirubinemias that underlie Crigler-Najjars syndrome (Ritter et al., 1993) and ...
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6-Thiopurine (6TP) is an actively prescribed drug in the treatment of various diseases ranging from Crohns disease and other inflammatory diseases to acute lymphocytic leukemia and non-Hodgkins leukemia. While 6TP has beneficial therapeutic uses, severe toxicities are also reported with its use, such as jaundice and liver toxicity. While numerous investigations into the mode in which toxicity originates has been undertaken. None have investigated the effects of inhibition towards UDP-Glucose Dehydrogenase (UDPGDH), an oxidative enzyme responsible for UDP-glucuronic acid (UDPGA) formation or UDP-Glucuronosyl transferase (UGT1A1), which is responsible for the conjugation of bilirubin with UDPGA for excretion ...
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CYP3A4, CYP2C9, CYP2C19 and UGT Substrates: ERLEADA is a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use of ERLEADA with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications. Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued. Concomitant administration of ERLEADA with medications that are substrates of UDP-glucuronosyl transferase (UGT) can result in decreased exposure. Use caution if substrates of UGT must be co-administered with ERLEADA and evaluate for loss of activity ...
Accepted name: N-acetylgalactosaminyl-proteoglycan 3-β-glucuronosyltransferase. Reaction: UDP-α-D-glucuronate + N-acetyl-β-D-galactosaminyl-(1→4)-β-D-glucuronosyl-proteoglycan = UDP + β-D-glucuronosyl-(1→3)-N-acetyl-β-D-galactosaminyl-(1→4)-β-D-glucuronosyl-proteoglycan. For diagram click here.. Other name(s): chondroitin glucuronyltransferase II. Systematic name: α-D-glucuronate:N-acetyl-β-D-galactosaminyl-(1→4)-β-D-glucuronosyl-proteoglycan 3-β-glucuronosyltransferase. Comments: Involved in the biosynthesis of chondroitin and dermatan sulfate. The human chondroitin synthetase is a bifunctional glycosyltransferase, which has the 3-β-glucuronosyltransferase and 4-β-N-acetylgalactosaminyltransferase (EC 2.4.1.175) activities required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase co-polymerases can be found in Pasteurella multocida and Escherichia coli. There is also another human protein with apparently only the ...
4133 Individualized, tailored drug therapy is an important direction for development of cancer treatment. Currently, irinotecan (CPT-11) has been widely used in a variety of human cancers. Occasionally, occurrence of unexpected severe toxicities (Gr. 4 neutropenia, Gr. 4 diarrhea, sepsis) of irinotecan may hinder its clinical use. Irinotecan is activated by carboxylesterase to SN-38 with its antitumor activity, and which has been associated with the severe diarrheal episodes as a result of the direct enteric injury. SN-38 undergoes glucuronide conjugation and inactivation by UDP-glucuronosyl transferase 1A1 (UGT1A1) isoform to form the inactive SN-38 glucuronide (SN-38G). Among the UGT1A1 polymorphism, the UGT1A1*28 genotype, with (TA)7TAA change of UGT1A1 gene promoter, had probable important implications to predict and monitor clinical toxicity induced by irinotecan. We tried to analyze the polymorphisms in UGT1A1*28 genotype as predictors of severe toxic events occurring after irinotecan ...
Resveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologic doses of resveratrol on drug- and carcinogen-metabolizing enzymes. Forty-two healthy volunteers underwent baseline assessment of cytochrome P450 (CYP) and phase II detoxification enzymes. CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzyme activities were measured by the metabolism of caffeine, dextromethorphan, losartan, and buspirone, respectively. Blood lymphocyte glutathione S-transferase (GST) activity and GST-π level and serum total and direct bilirubin, a surrogate for UDP-glucuronosyl transferase (UGT) 1A1 activity, were measured to assess phase II enzymes. After the baseline evaluation, study participants took 1 g of resveratrol once daily for 4 weeks. Enzyme assessment was repeated upon intervention completion. Resveratrol intervention was found to inhibit the phenotypic indices of CYP3A4, CYP2D6, and CYP2C9 and to induce the ...
1. A stable, more highly purified, preparation of UDP-glucuronyltransferase was obtained than previously reported. 2. Enzyme activity towards o-aminophenyl and p-nitrophenyl was increased 43- and 46-fold respectively. 3. The final preparation contains only three staining polypeptide bands visible after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 4. The only known major accompanying protein appears to be epoxide hydratase. 5. The purified enzyme activity towards o-aminophenol can still be activated 3 fold by diethylnitrosamine. 6. On evidence from purification, o-aminophenol and p-nitrophenol appear to be glucuronidated by the same enzyme protein. The possible recognition of the UDP-glucuronyltransferase enzyme is discussed. ...
1. Chen, H., Yang, K., Choi, S., Fischer, J. H. & Jeong, H. Up-regulation of UDP-glucuronosyltransferase (UGT) 1A4 by 17β-estradiol: A potential mechanism of increased lamotrigine elimination in pregnancy. Drug Metab. Dispos. 37, 1841-1847 (2009).. 2. Christensen, J. et al. Oral contraceptives induce lamotrigine metabolism: Evidence from a double-blind, placebo-controlled trial. Epilepsia 48, 484-489 (2007).. 3. Gulcebi, M. I. et al. The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy. Epilepsy Res. 95, 1-8 (2011).. 4. Johannessen, S. I. & Landmark, C. J. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 8, 254-267 (2010).. 5. Rowland, A., Elliot, D.J., Williams, A., Mackenzie, P.I., Dickinson, R.G., Miners, J. O. IN VITRO CHARACTERIZATION OF LAMOTRIGINE N 2-GLUCURONIDATION AND THE LAMOTRIGINE-VALPROIC ACID INTERACTION Andrew Rowland , David J . Elliot , J . Andrew Williams , Peter I . Mackenzie ...
Like with humans, obese dogs are definitely more likely to snore over the night. • If there is often a need to get a database. internal stimuli which could cause the crooks to malfunction. See the extraordinary view in the rooftops. This is the place where UGT or urodine diphosphate glucuronosyltransferase can be purchased in, it can help the liver cells process the bilirubin into bile. Besides, all auto producers promises to get the best sort of hybrid cars inside the market today. It is that you who will going to discover each day the destruction your artist has created in your body. own parachute whenever you exit the airplane, but exit with two. Las canciones mas conocidas de aquel disco don "Underneath Your Clothes" (debajo de tu ropa) y "Whenever, Wherever" (Suerte) fueron los mas populares. Accessories for Coin Collection ...
Complete information for UGT1A7 gene (Protein Coding), UDP Glucuronosyltransferase Family 1 Member A7, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for UGT1A13P gene (Pseudogene), UDP Glucuronosyltransferase Family 1 Member A13, Pseudogene, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Since many drugs are cytochrome P450 (CYP)-3A4 substrates, it has become common practice to assess drug-drug interaction (DDI) potential with a CYP3A4 inhibitor (ketoconazole) or inducer (rifampicin) in early drug development. Such an evaluation is relevant to anticancer drugs with metabolism governed by CYP3A4. DDIs with rifampicin are complex, involving other physiological mechanisms that may impact overall pharmacokinetics. Our objective was to study and delineate such mechanisms for oral versus intravenous anticancer drugs. We hypothesized that DDIs between anticancer drugs and rifampicin were primarily driven by CYP3A4 induction. This hypothesis was proven for the oral anticancer drugs; however, in some cases, other intrinsic mechanisms such as P-glycoprotein (Pgp)/UDP glucuronosyl transferase (UGT) induction and transporter inhibition may have played an important role alongside the induced CYP3A4 enzymes. The hypothesis that CYP3A4 induction would decrease drug exposure appeared paradoxical for
Background: The UDP-Glucuronosyltransferases (UGTs) are phase II metabolic enzymes that prime endogenous and exogenous compounds for excretion from the body. The UGTs are often found to have high inter-individual differences in expression, and this impacts patients response to drug therapy. Studies examining the epigenetic regulation of the UGT enzymes have not previously been performed. Recently, it has been shown that the phase I metabolic cytochrome P-450s (CYPs) are negatively regulated by microRNA (miRNA). miRNA are short, endogenous strands of RNA roughly 22-24 nucleotides in length that regulate gene expression. MiRNA specifically bind to the 3 untranslated region (UTR) of mature messenger RNA (mRNA) and post-transcriptionally repress protein expression. Purpose: The goal of this study is to identify and evaluate miRNA regulation of UGT1A expression and whether this regulation contributes to differences in UGT1A enzymatic activity. Results: miR-491-3p was identified using the miRanda ...
UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Active on odorants and seems to be involved in olfaction; it could help clear lipophilic odorant molecules from the sensory epithelium.
Biotransformation reactions are classified into two types: phase I (nonsynthetic) and phase II (synthetic) reactions. Phase I reactions include oxidations, reductions, and hydrolysis reactions. These reactions typically introduce functional groups (ie, -OH, -SH, -NH2) that serve as active centers for subsequent phase II reactions. Enzymes catalyzing phase I reactions include cytochrome P450, aldehyde dehydrogenase, alcohol dehydrogenase, monoamine oxidase, deaminases, esterases, amidases, and epoxide hydrolase. Phase II reactions are conjugation reactions, involving an enzyme-catalyzed combination of endogenous compounds to functional groups produced from phase I reactions. These reactions utilize energy from "activated" forms of the endogenous compounds (ie, acetyl-CoA, UDP-glucuronate, glutathione). Enzymes catalyzing phase II reactions include glucuronyl transferase (conjugates glucuronyl group), sulfotransferase (conjugates sulfate group), transacylases (conjugates amino acids), glutathione ...
CONCLUSIONS: For studies of glucuronidation of xenobiotics where the role UGT1A6 is expected, the use of pig and monkey microsomes should be considered. As an optimal model for study of silybin glucuronidation, both the rhesus monkey and dog (Beagle) seem to be the best models. To elucidate the role of the UGT forms involved in metabolism of silybin, the experiments with recombinant UGT enzymes are needed..... Read abstract Full text PDF ...
1999 (English)In: In: Gene Therapy and Molecular Biology. From basic mechanisms to clinical applications (T. Boulikas, ed.), Gene Therapy Press, Palo Alto , 1999, Vol. 3, 465- p.Chapter in book (Other scientific) ...
Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, ...
Mouse Monoclonal Anti-beta-1,3-Glucuronyltransferase 1/B3GAT1 Antibody (HCD57). Validated: Flow. Tested Reactivity: Human. 100% Guaranteed.
Cytochrome P450 (CYP) proteins compose a highly diverse superfamily found in all domains of life. These proteins are enzymes involved in metabolism of endogenous and exogenous compounds. In vertebrate
LC-MS/MS is a valuable tool in clinical research applications, enabling reliable multi-component measurement of many endogenous/exogenous compounds at low concentration. For many applications LC-MS is now the technique of choice for clinical research.
UGT genes (indicated by number following subfamily letter) show ~100% identity Slightly less than 100% identity may be found for allelic variants (same gene).. Note: These family and subfamily percent identity cut-offs are only considered guidelines. Adherence to these limits tends to change over time often in an attempt to cluster similar families and subfamilies as the numbers of available sequences in each group has grown ...
TY - JOUR. T1 - Dismutation of Bilirubin Monoglucuronide. AU - Chowdhury, J. Roy. AU - Arias, Irwin M.. PY - 1981/1/1. Y1 - 1981/1/1. N2 - Bilirubin monoglucuronide is the major pigment in the human and rat bile. The dismutation of bilirubin monoglucuronide occurs at a normal rate in vitro in the liver of uridine diphosphate glucuronosyltransferase deficient man and rat. This chapter presents a procedure for the isolation of azopigmcnts. Preparations procedure involves the preparation of rat liver microsomes; the biosynthesis of bilirubin monoglucuronide; and the preparation of ethyl anthranilate diazo reagent. In the assay, the enzyme suspension is incubated with sodium phosphate at pH 6.6 containing glucaro-l,4-lactonc. Bilirubin monoglucuronide is dissolved in Tris-HCl at pH 7.8 and 0.05 ml is added to the enzyme-buffer mixture. After incubation at 37 ° for 3 min, the reaction is stopped with 2 ml ice-cold ethyl anthranilate diazo reagent. After incubation at 25 ° for 30min, 1ml of 20% ...
TY - JOUR. T1 - A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler-Najjar Type I patient generates a pH-sensitive bilirubin UDP-glucuronosyltransferase. AU - Ritter, Joseph K.. AU - Yeatman, Matthew T.. AU - Kaiser, Charlotte. AU - Gridelli, Bruno. AU - Owens, Ida S.. PY - 1993/11/5. Y1 - 1993/11/5. N2 - The characterization (Ritter, J. K., Chen, F., Sheen, Y. Y., Tran, H. M., Kimura, S., Yeatman, M. T., and Owens, I. S. (1992) J. Biol. Chem. 267, 3257-3261) of the single-copy UGT1 gene complex encoding both bilirubin and phenol UDP-glucuronosyltransferases (transferase) has been critical to the determination of genetic defects in Crigler-Najjar Type I patients. The complex (UGT1A-UGT1G) codes for at least two bilirubin, three bilirubin-like, and two phenol transferases. Seven different exons 1, each with an upstream promoter and each encoding the amino terminus of an isoform, are arrayed in series with four common exons (encoding seven identical carboxyl termini) in the ...
GSK1349572 is an integrase inhibitor that is currently in clinical development for the treatment of human immunodeficiency virus (HIV) infection. GSK1349572 is metabolized primarily by uridine diphosphate glucuronosyltransferase (UGT)1A1 with a minor role of Cytochrome P450 (CYP)3A. Hepatic impairment could potentially alter the clearance and plasma protein binding of GSK1349572. This study will evaluate the single dose pharmacokinetics and safety of GSK1349572 in healthy subjects and in subjects with mild or moderate hepatic impairment based on Child-Pugh category.. This is a single-dose, open-label, parallel group, two-part, adaptive study in adult males and females with mild or moderate hepatic impairment and matched, healthy control subjects with normal hepatic function. Healthy control subjects (16) will be matched for gender, age, and BMI to the subjects in the mild (8) or moderate (8) hepatic impairment category. In Part 1, approximately 8 subjects with moderate hepatic impairment (cohort ...
GSK1349572 is an integrase inhibitor that is currently in clinical development for the treatment of human immunodeficiency virus (HIV) infection. GSK1349572 is metabolized primarily by uridine diphosphate glucuronosyltransferase (UGT)1A1 with a minor role of Cytochrome P450 (CYP)3A. Hepatic impairment could potentially alter the clearance and plasma protein binding of GSK1349572. This study will evaluate the single dose pharmacokinetics and safety of GSK1349572 in healthy subjects and in subjects with mild or moderate hepatic impairment based on Child-Pugh category.. This is a single-dose, open-label, parallel group, two-part, adaptive study in adult males and females with mild or moderate hepatic impairment and matched, healthy control subjects with normal hepatic function. Healthy control subjects (16) will be matched for gender, age, and BMI to the subjects in the mild (8) or moderate (8) hepatic impairment category. In Part 1, approximately 8 subjects with moderate hepatic impairment (cohort ...
The C-8 phenol group is essential to exert the bioactivities of daphnetin, but it is readily conjugated with glucuronic acid prior to excretion. In this study, daphnetin-7-methylether (7M-DNP) was used to investigate the effect of 7-methyl substitution on daphnetin glucuronidation in human/rat liver (HLM/RLM) and intestine (HIM/RIM) microsomes, and recombinant UDP-glucuronosyltransferases (UGTs). Compared with daphnetin, the V-max/K-m values of 7M-DNP via 8-O-glucuronidation were 2.1-fold lower in HLM, 1.7-fold lower in HIM, and 2.4-fold lower in RLM, suggesting an improvement in metabolic stability. Different from daphnetin 8-O-glucuronidation exclusively catalyzed by UGT1A6 and UGT1A9, UGT1A1, -1A3, -1A7, -1A8, and -1A9 showed glucuronidation activity toward 7M-DNP. Kinetics studies, chemical inhibition, and the relative activity factor approach were used to demonstrate that UGT1A9 was mainly responsible for the reaction in HLM, whereas UGT1A1 was a primary contributor in HIM. The V-max/K-m ...
Definition of UDPglucuronate-bilirubin glucuronosyltransferase. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.