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https://www.readbyqxmd.com/read/29148714/evaluating-the-rate-and-substrate-specificity-of-laboratory-evolved-xna-polymerases
#1
Ali Nikoomanzar, Matthew R Dunn, John C Chaput
Engineered polymerases that can copy genetic information between DNA and xeno-nucleic acids (XNA) hold tremendous value as reagents in future bio-technology applications. However, current XNA poly-merases function with inferior activity relative to their natural counterparts, indicating that current polymerase engineering efforts would benefit from new benchmark-ing assays. Here, we describe a highly parallel, low cost method for measuring the average rate and substrate specificity of XNA polymerases in a standard qPCR instrument...
November 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29134333/whole-cell-dependent-biosynthesis-of-sulfo-conjugate-using-human-sulfotransferase-expressing-budding-yeast
#2
Miyu Nishikawa, Yuuka Masuyama, Motomichi Nunome, Kaori Yasuda, Toshiyuki Sakaki, Shinichi Ikushiro
Cytosolic sulfotransferases (SULTs), one of the predominant phase II drug metabolizing enzymes (DME), play important roles in metabolism of xeno- and endobiotics to generate their sulfo-conjugates. These sulfo-conjugates often have biological activities but are difficult to study, because even though only small amounts are required to evaluate their efficacy and safety, chemical or biological synthesis of sulfo-conjugatesis is often challenging. Previously, we constructed a DME expression system for cytochrome P450 and UGT, using yeast cells, and successfully produced xenobiotic metabolites in a whole-cell-dependent manner...
November 13, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29130021/transgenic-overexpression-of-steroid-sulfatase-alleviates-cholestasis
#3
Mengxi Jiang, Meishu Xu, Songrong Ren, Kyle W Selcer, Wen Xie
Background and Aim: Sulfotransferase (SULT)-mediated sulfation and steroid sulfatase (STS)-mediated desulfation represent two critical mechanisms that regulate the chemical and functional homeostasis of endogenous and exogenous molecules. STS catalyzes the hydrolysis of steroid sulfates to form hydroxysteroids. Oxygenated cholesterol derivative oxysterols are known to be endogenous ligands of the liver X receptor (LXR), a nuclear receptor with anti-cholestasis activity, whereas the sulfated oxysterols antagonize LXR signaling...
June 2017: Liver Res
https://www.readbyqxmd.com/read/29126297/tellurate-enters-escherichia-coli-k-12-cells-via-the-sult-type-sulfate-transporter-cyspuwa
#4
Jennifer Goff, Nathan Yee
Soluble forms of tellurium are environmental contaminants that are toxic to microorganisms. While tellurite [Te(IV)] is a well-characterized antimicrobial agent, little is known about the interactions of tellurate [Te(VI)] with bacterial cells. In this study, we investigated the role of sulfate transporters in the uptake of tellurate in Escherichia coli K-12. Mutant strains carrying a deletion of the cysW gene in the CysPUWA sulfate transporter system accumulated less cellular tellurium and exhibited higher resistance to tellurate compared to the wild type strain...
November 6, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29109113/generation-and-characterization-of-sult4a1-mutant-mouse-models
#5
Patrick L Garcia, Mohammed I Hossain, Shaida A Andrabi, Charles N Falany
Sulfotransferase 4A1 (SULT4A1) belongs to the cytosolic sulfotransferase (SULT) superfamily of enzymes that catalyze sulfonation reactions with a variety of endogenous and exogenous substrates. Of the SULTs, SULT4A1 was shown to have the highest sequence homology between vertebrate species, yet no known function or enzymatic activity have been identified for this orphan SULT. To better understand SULT4A1 function in mammalian brain, two mutant SULT4A1 mouse strains were generated utilizing CRISPR-Cas9 technology...
November 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29090664/pharmacogenetics-of-metabolic-genes-of-anthracyclines-in-acute-myeloid-leukemia
#6
Juan Eduardo Megias-Vericat, David Martinez-Cuadron, Maria Jose Herrero, Salvador F Alino, Jose Luis Poveda, Miguel Angel Sanz, Pau Montesinos
BACKGROUND: Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes. METHODS: A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity...
November 1, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29074051/the-inhibitory-effects-of-%C3%AE-caryophyllene-%C3%AE-caryophyllene-oxide-and-%C3%AE-humulene-on-the-activities-of-the-main-drug-metabolizing-enzymes-in-rat-and-human-liver-in-vitro
#7
Linh Thuy Nguyen, Zuzana Myslivečková, Barbora Szotáková, Alena Špičáková, Kateřina Lněničková, Martin Ambrož, Vladimír Kubíček, Kristýna Krasulová, Pavel Anzenbacher, Lenka Skálová
Sesquiterpenes, the main components of plant essential oils, are often taken in the form of folk medicines and dietary supplements. Several sesquiterpenes possess interesting biological activities but they could interact with concurrently administered drugs via inhibition of drug-metabolizing enzymes. Therefore, the present study was designed to test the potential inhibitory effect of tree structurally relative sesquiterpenes β-caryophyllene (CAR), β-caryophyllene oxide (CAO) and α-humulene (HUM) on the activities of the main drug-metabolizing enzymes...
October 23, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29038294/the-nsaid-allosteric-site-of-human-cytosolic-sulfotransferases
#8
Ting Wang, Ian Cook, Thomas S Leyh
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs worldwide - more than 111 million prescriptions were written in the United Sates in 2014. NSAIDs allosterically inhibit cytosolic sulfotransferases (SULTs) with high specificity and therapeutically relevant affinities. The current study focuses on the interactions of SULT1A1 and mefenamic acid (MEF) - a potent, highly specific NSAID inhibitor of 1A1. Here, the first structure of an NSAID allosteric site - the MEF-binding site of SULT1A1 - is determined using spin-label-triangulation NMR...
October 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29022574/osthole-prevents-acetaminophen-induced-liver-injury-in-mice
#9
Yun Cai, Wu Sun, Xin-Xin Zhang, Yan-Die Lin, Hao Chen, Hao Li
Acetaminophen (APAP) overdose leads to severe hepatotoxicity. Osthole, a natural coumarin found in traditional Chinese medicinal herbs, has therapeutic potential in the treatment of various diseases. In this study, we investigated the effects of osthole against APAP-induced hepatotoxicity in mice. Mice were administered osthole (100 mg·kg(-1)·d(-1), ip) for 3 d, then on the fourth day APAP (300 mg/kg, ip) was co-administered with osthole. The mice were euthanized post-APAP, their serum and livers were collected for analysis...
October 12, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28992322/human-cytosolic-sulphotransferase-sult1c3-genomic-analysis-and-functional-characterization-of-splice-variant-sult1c3a-and-sult1c3d
#10
Katsuhisa Kurogi, Takehiko Shimohira, Haruna Kouriki-Nagatomo, Guisheng Zhang, Ethan R Miller, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
The cytosolic sulphotransferase SULT1C3 remained the most poorly understood human SULT. The SULT1C3 gene has been shown to contain alternative exons 7 and 8, raising the question concerning their evolutionary origin and implying the generation of multiple SULT1C3 variants. Two SULT1C3 splice variants, SULT1C3a and SULT1C3d, were investigated to verify the impact of alternative C-terminal sequences on their sulphating activity. Sequence homology and gene location analyses were performed to verify the orthology of the SULT1C3 gene...
June 29, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28970781/non-digestible-stachyose-promotes-bioavailability-of-genistein-through-inhibiting-intestinal-degradation-and-first-pass-metabolism-of-genistein-in-mice
#11
Yalong Lu, Dehui Lin, Wenfeng Li, Xingbin Yang
This study was designed to explore the molecular mechanism of stachyose in enhancing the gastrointestinal stability and absorption of soybean genistein in mice. Male Kunming mice in each group (n = 8) were administered by intragastric gavage with saline, stachyose (250 mg/kg·bw), genistein (100 mg/kg·bw), and stachyose (50, 250, and 500 mg/kg·bw) together with genistein (100 mg/kg·bw) for 4 consecutive weeks, respectively, and then their urine, feces, blood, gut, and liver were collected. UPLC-qTOF/MS analysis showed that levels of genistein and its metabolites (dihydrogenistein, genistein 7-sulfate sodium salt, genistein 4'-β-D-glucuronide, and genistein 7-β-D-glucuronide) in serum and urine were increased with an increase in stachyose dosages in mice...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28970022/stereoselective-degradation-and-thyroid-endocrine-disruption-of-lambda-cyhalothrin-in-lizards-eremias-argus-following-oral-exposure
#12
Jing Chang, Weiyu Hao, Yuanyuan Xu, Peng Xu, Wei Li, Jianzhong Li, Huili Wang
The disturbance of the thyroid system and elimination of chiral pyrethroid pesticides with respect to enantioselectivity in reptiles have so far received limited attention by research. In this study, bioaccumulation, thyroid gland lesions, thyroid hormone levels, and hypothalamus-pituitary-thyroid axis-related gene expression in male Eremias argus were investigated after three weeks oral administration of lambda-cyhalothrin (LCT) enantiomers. In the lizard liver, the concentration of LCT was negatively correlated with the metabolite-3-phenoxybenzoic acid (PBA) level during 21 days of exposure...
September 29, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28933499/multi-biomarker-approach-in-the-scallop-chlamys-farreri-to-assess-pahs-pollution-in-qingdao-coastal-areas-of-china
#13
Luqing Pan, Mengyu Zhang, Qian Jin, Rongwang Ji
A multi-biomarker approach was conducted in the scallop Chlamys farreri from three sites, denoted here as S1, S2, and S3, in Qingdao coastal areas of China in March, June, September and December 2014 to assess pollution from polycyclic aromatic hydrocarbons (PAHs) and to select appropriate biomarkers. A suite of biological responses of the gills and digestive glands of the scallops was assayed, including: (i) phase I detoxification enzymes of 7-ethoxyresorufin-O-deethylase (EROD), epoxide hydrolase (EH), and dihydrodiol dehydrogenase (DD) and phase II detoxification enzymes of glutathione-S-transferase (GST) and sulfotransferase (SULT); (ii) antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx); (iii) oxidative damage parameters: lipid peroxidation (LPO) expressed by malondialdehyde (MDA) contents, protein carbonylation (PC) and DNA damage (F value); and (iv) the metabolism-related genes of EH, DD, GST, SULT and SOD...
November 15, 2017: Environmental Science. Processes & Impacts
https://www.readbyqxmd.com/read/28911247/metabolic-pathways-and-pharmacokinetics-of-natural-medicines-with-low-permeability
#14
Mei Zeng, Lan Yang, Dan He, Yao Li, Mingxin Shi, Jingqing Zhang
Drug metabolism plays an important role in the drug disposal process. Differences in pharmacokinetics among individuals are the basis for personalized medicine. Natural medicines, formed by long-term evolution of nature, prioritize the action of a target protein with a drug. Natural medicines are valued for structural diversity, low toxicity, low cost, and definite biological activities. Metabolic pathway and pharmacokinetic research of natural medicines is highly beneficial for clinical dose adjustment and the development of personalized medicine...
September 14, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28875717/sult1a1-copy-number-variation-ethnic-distribution-analysis-in-an-indian-population
#15
Suhani Almal, Harish Padh
Cytosolic sulfotransferases (SULTs) are phase II detoxification enzymes involved in metabolism of numerous xenobiotics, drugs and endogenous compounds. Interindividual variation in sulfonation capacity is important for determining an individual's response to xenobiotics. SNPs in SULTs, mainly SULT1A1 have been associated with cancer risk and also with response to therapeutic agents. Copy number variation (CNVs) in SULT1A1 is found to be correlated with altered enzyme activity. This short report primarily focuses on CNV in SULT1A1 and its distribution among different ethnic populations around the globe...
September 24, 2017: Annals of Human Biology
https://www.readbyqxmd.com/read/28867356/relationship-of-sult1a1-copy-number-variation-with-estrogen-metabolism-and-human-health
#16
Jixia Liu, Ran Zhao, Zhan Ye, Alexander J Frey, Emily R Schriver, Nathaniel W Snyder, Scott J Hebbring
Human cytosolic sulfotransferase 1A1 (SULT1A1) is considered to be one of the most important SULT isoforms for metabolism, detoxification, and carcinogenesis. This theory is driven by observations that SULT1A1 is widely expressed in multiple tissues and acts on a wide range of phenolic substrates. SULT1A1 is subject to functional common copy number variation (CNV) including deletions or duplications. However, it is less clear how SULT1A1 CNV impacts health and disease. To better understand the biological role of SULT1A1 in human health, we genotyped CNV in 14,275 Marshfield Clinic patients linked to an extensive electronic health record...
November 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28807679/identification-and-characterization-of-5%C3%AE-cyprinol-sulfating-cytosolic-sulfotransferases-sults-in-the-zebrafish-danio-rerio
#17
Katsuhisa Kurogi, Maki Yoshihama, Austin Horton, Isaac T Schiefer, Matthew D Krasowski, Lee R Hagey, Frederick E Williams, Yoichi Sakakibara, Naoya Kenmochi, Masahito Suiko, Ming-Cheh Liu
5α-Cyprinol 27-sulfate is the major biliary bile salt present in cypriniform fish including the zebrafish (Danio rerio). The current study was designed to identify the zebrafish cytosolic sulfotransferase (Sult) enzyme(s) capable of sulfating 5α-cyprinol and to characterize the zebrafish 5α-cyprinol-sulfating Sults in comparison with human SULT2A1. Enzymatic assays using zebrafish homogenates showed 5α-cyprinol-sulfating activity. A systematic analysis, using a panel of recombinant zebrafish Sults, revealed two Sult2 subfamily members, Sult2st2 and Sult2st3, as major 5α-cyprinol-sulfating Sults...
November 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28802998/on-the-sulfation-of-o-desmethyltramadol-by-human-cytosolic-sulfotransferases
#18
Mohammed I Rasool, Ahsan F Bairam, Katsuhisa Kurogi, Ming-Cheh Liu
BACKGROUND: Previous studies have demonstrated that sulfate conjugation is involved in the metabolism of the active metabolite of tramadol, O-desmethyltramadol (O-DMT). The current study aimed to systematically identify the human cytosolic sulfotransferases (SULTs) that are capable of mediating the sulfation of O-DMT. METHODS: The sulfation of O-DMT under metabolic conditions was demonstrated using HepG2 hepatoma cells and Caco-2 human colon carcinoma cells. O-DMT-sulfating activity of thirteen known human SULTs and four human organ specimens was examined using an established sulfotransferase assay...
February 16, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28782626/%C3%AE-4-3-ketosteroids-as-a-new-class-of-substrates-for-the-cytosolic-sulfotransferases
#19
Takuyu Hashiguchi, Katsuhisa Kurogi, Takehiko Shimohira, Takamasa Teramoto, Ming-Cheh Liu, Masahito Suiko, Yoichi Sakakibara
Cytosolic sulfotransferase (SULT)-mediated sulfation is generally known to involve the transfer of a sulfonate group from the active sulfate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), to a hydroxyl group or an amino group of a substrate compound. We report here that human SULT2A1, in addition to being able to sulfate dehydroepiandrosterone (DHEA) and other hydroxysteroids, could also catalyze the sulfation of Δ(4)-3-ketosteroids, which carry no hydroxyl groups in their chemical structure. Among a panel of Δ(4)-3-ketosteroids tested as substrates, 4-androstene-3,17-dione and progesterone were found to be sulfated by SULT2A1...
November 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28762319/quantification-of-sulfotransferase-1a-isoforms-in-human-tissue-fractions-and-cell-lines-by-multiple-reaction-monitoring-mass-spectrometry
#20
Sho Yoshitake, Melissa McKay-Daily, Masaki Tanaka, Zeqi Huang
BACKGROUND: Within the sulfotransferase (SULT) superfamily of metabolic enzymes, the SULT1A family of cytosolic sulfotransferases is of particular interest, due to its ability to catalyze the sulfation of phenolic substrates. In humans, there are three distinct SULT1A enzymes: SULT1A1, SULT1A2, and SULT1A3/4. OBJECTIVE: To detect and quantify these enzymes in S9 fractions and cell lines using targeted mass spectrometry-based proteomics. METHOD: Samples were tryptically digested, and signature peptides were quantified using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM/MS)...
July 31, 2017: Drug Metabolism Letters
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