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The UDP-glucuronosyltransferases: their role in drug metabolism and detoxification.
Rowland A, Miners JO, Mackenzie PI. Rowland A, et al. Int J Biochem Cell Biol. 2013 Jun;45(6):1121-32. doi: 10.1016/j.biocel.2013.02.019. Epub 2013 Mar 7. Int J Biochem Cell Biol. 2013. PMID: 23500526 Review.
Human UDP-glucuronosyltransferase (UGT) exists as a superfamily of 22 proteins, which are divided into 5 families and 6 subfamilies on the basis of sequence identity. ...These enzymes primarily catalyse the covalent linkage of glucuronic acid, derived from the cofactor UDP …
Human UDP-glucuronosyltransferase (UGT) exists as a superfamily of 22 proteins, which are divided into 5 families and 6 subfamilies o …
In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction.
Rowland A, Elliot DJ, Williams JA, Mackenzie PI, Dickinson RG, Miners JO. Rowland A, et al. Drug Metab Dispos. 2006 Jun;34(6):1055-62. doi: 10.1124/dmd.106.009340. Epub 2006 Mar 24. Drug Metab Dispos. 2006. PMID: 16565174
LTG N2-glucuronidation by microsomes from five livers exhibited atypical kinetics, best described by a model comprising the expressions for the Hill (1869 +/- 1286 microM, n = 0.65 +/- 0.16) and Michaelis-Menten (Km 2234 +/- 774 microM) equations. ...LTG N2-glucuronidation …
LTG N2-glucuronidation by microsomes from five livers exhibited atypical kinetics, best described by a model comprising the expressio …
Binding of inhibitory fatty acids is responsible for the enhancement of UDP-glucuronosyltransferase 2B7 activity by albumin: implications for in vitro-in vivo extrapolation.
Rowland A, Gaganis P, Elliot DJ, Mackenzie PI, Knights KM, Miners JO. Rowland A, et al. J Pharmacol Exp Ther. 2007 Apr;321(1):137-47. doi: 10.1124/jpet.106.118216. Epub 2007 Jan 19. J Pharmacol Exp Ther. 2007. PMID: 17237258
Addition of bovine serum albumin (BSA) and fatty acid-free human serum albumin (HSA-FAF), but not "crude" HSA, resulted in an approximate 90% reduction in the Km values for the glucuronidation of zidovudine (AZT) by human liver microsomes (HLM) and UGT2B7 and a 50 to 75% r …
Addition of bovine serum albumin (BSA) and fatty acid-free human serum albumin (HSA-FAF), but not "crude" HSA, resulted in an approximate 90 …
The "albumin effect" and drug glucuronidation: bovine serum albumin and fatty acid-free human serum albumin enhance the glucuronidation of UDP-glucuronosyltransferase (UGT) 1A9 substrates but not UGT1A1 and UGT1A6 activities.
Rowland A, Knights KM, Mackenzie PI, Miners JO. Rowland A, et al. Drug Metab Dispos. 2008 Jun;36(6):1056-62. doi: 10.1124/dmd.108.021105. Epub 2008 Mar 24. Drug Metab Dispos. 2008. PMID: 18362158
Arachidonic, linoleic, and oleic acids and a mixture of these decreased the rates of 4MU and PRO glucuronidation by UGT1A9. K(m) values for these reactions were increased 3- to 6-fold by the fatty acid mixture. ...Only BSA caused a similar effect on 4MU glucuronidat …
Arachidonic, linoleic, and oleic acids and a mixture of these decreased the rates of 4MU and PRO glucuronidation by UGT1A9. K(m) valu …
Characterization of the binding of drugs to human intestinal fatty acid binding protein (IFABP): potential role of IFABP as an alternative to albumin for in vitro-in vivo extrapolation of drug kinetic parameters.
Rowland A, Knights KM, Mackenzie PI, Miners JO. Rowland A, et al. Drug Metab Dispos. 2009 Jul;37(7):1395-403. doi: 10.1124/dmd.109.027656. Epub 2009 Apr 27. Drug Metab Dispos. 2009. PMID: 19398502
Of the compounds screened, highest binding to IFABP was observed for sulfinpyrazone (an acid) and beta-estradiol (a neutral compound). ...Each protein reduced the K(m) for AZT glucuronidation in a concentration-dependent manner, although a higher content of I …
Of the compounds screened, highest binding to IFABP was observed for sulfinpyrazone (an acid) and beta-estradiol (a neutral compound) …
Effects of amino acid substitutions at positions 33 and 37 on UDP-glucuronosyltransferase 1A9 (UGT1A9) activity and substrate selectivity.
Korprasertthaworn P, Rowland A, Lewis BC, Mackenzie PI, Yoovathaworn K, Miners JO. Korprasertthaworn P, et al. Among authors: rowland a. Biochem Pharmacol. 2012 Dec 1;84(11):1511-21. doi: 10.1016/j.bcp.2012.08.026. Epub 2012 Sep 5. Biochem Pharmacol. 2012. PMID: 22981363
To elucidate the roles of key amino acids and characterise structure-function relationships, we determined the effects of amino acid substitutions at positions 33 and 37 of UGT1A9 on the kinetics of 4-methylumbelliferone (4-MU), mycophenolic acid (MPA), propofol (PRO), sulfinpyra …
To elucidate the roles of key amino acids and characterise structure-function relationships, we determined the effects of amino acid substit …
Renal drug metabolism in humans: the potential for drug-endobiotic interactions involving cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT).
Knights KM, Rowland A, Miners JO. Knights KM, et al. Among authors: rowland a. Br J Clin Pharmacol. 2013 Oct;76(4):587-602. doi: 10.1111/bcp.12086. Br J Clin Pharmacol. 2013. PMID: 23362865 Free PMC article. Review.
The most abundantly expressed renal UGTs are 1A9 and 2B7, which play a significant role in the glucuronidation of drugs, arachidonic acid, prostaglandins, leukotrienes and P450 derived arachidonic acid metabolites. ...
The most abundantly expressed renal UGTs are 1A9 and 2B7, which play a significant role in the glucuronidation of drugs, arachidonic …
Cytochrome P450 and ischemic heart disease: current concepts and future directions.
Rowland A, Mangoni AA. Rowland A, et al. Expert Opin Drug Metab Toxicol. 2014 Feb;10(2):191-213. doi: 10.1517/17425255.2014.859675. Epub 2013 Nov 25. Expert Opin Drug Metab Toxicol. 2014. PMID: 24274646 Review.
Inhibition of human drug-metabolising cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in vitro by uremic toxins.
Barnes KJ, Rowland A, Polasek TM, Miners JO. Barnes KJ, et al. Among authors: rowland a. Eur J Clin Pharmacol. 2014 Sep;70(9):1097-106. doi: 10.1007/s00228-014-1709-7. Epub 2014 Jun 24. Eur J Clin Pharmacol. 2014. PMID: 24954688
RESULTS: The individual uremic toxins inhibited CYP and UGT enzymes to a variable extent. p-Cresol was the most potent individual inhibitor, producing >50% inhibition of CYP2E1, CYP3A4, UGT1A1, UGT1A9 and UGT2B7 at a concentration of 100 μM. ...A combinati …
RESULTS: The individual uremic toxins inhibited CYP and UGT enzymes to a variable extent. p-Cresol was the most potent individual inh …
Transporter-mediated uptake of UDP-glucuronic acid by human liver microsomes: assay conditions, kinetics, and inhibition.
Rowland A, Mackenzie PI, Miners JO. Rowland A, et al. Drug Metab Dispos. 2015 Jan;43(1):147-53. doi: 10.1124/dmd.114.060509. Epub 2014 Nov 7. Drug Metab Dispos. 2015. PMID: 25380805
Furthermore, interaction studies undertaken with a panel of drugs, alternate UDP-sugars, and glucuronide conjugates, at low (2.5 μM) and high (1000 μM) UDP-GlcUA concentrations, demonstrated that both components were inhibited to varying extents. ...
Furthermore, interaction studies undertaken with a panel of drugs, alternate UDP-sugars, and glucuronide conjugates, at low (2.5 μM) …
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