What is UGT1A4?
The majority of drugs are metabolized to form compounds that are more polar in structure than their parental precursors. The ultimate goal is to 1) increase the hydrophilicity of the presented compounds along with their molecular weight, 2) inactivate their biological effects and 3) facilitate their efflux from the cells, subsequently followed by excretion into bile or urine1. The metabolic enzymes in charge of this process are traditionally organized into two separate categories; phase I (oxidation, reduction, or hydrolysis) and phase II (conjugation) enzymes1,2. During phase I, polar groups are added to the molecules through oxidation, reduction, and hydrolysis, mediated generally through cytochrome p450 enzymes. Phase II …show more content…
et al. Identification of aspartic acid and histidine residues mediating the reaction mechanism and the substrate specificity of the human UDP-glucuronosyltransferases 1A. The Journal of biological chemistry 282, 36514-36524, doi:10.1074/jbc.M703107200 …show more content…
I., Bowalgaha, K., Finel, M. & Miners, J. O. Influence of N-terminal domain histidine and proline residues on the substrate selectivities of human UDP-glucuronosyltransferase 1A1, 1A6, 1A9, 2B7, and 2B10. Drug metabolism and disposition: the biological fate of chemicals 37, 1948-1955, doi:10.1124/dmd.109.028225 (2009).
6 Ghosh, C. et al. Expression and functional relevance of UGT1A4 in a cohort of human drug-resistant epileptic brains. Epilepsia 54, 1562-1570, doi:10.1111/epi.12318 (2013).
7 Stingl, J. C., Bartels, H., Viviani, R., Lehmann, M. L. & Brockmoller, J. Relevance of UDP-glucuronosyltransferase polymorphisms for drug dosing: A quantitative systematic review. Pharmacology & therapeutics 141, 92-116, doi:10.1016/j.pharmthera.2013.09.002 (2014).
8 Rowland, A. et al. In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction. Drug metabolism and disposition: the biological fate of chemicals 34, 1055-1062, doi:10.1124/dmd.106.009340 (2006).
9 Gidal, B. E., Sheth, R., Parnell, J., Maloney, K. & Sale, M. Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Epilepsy research 57, 85-93, doi:10.1016/j.eplepsyres.2003.09.008
The majority of drugs are metabolized to form compounds that are more polar in structure than their parental precursors. The ultimate goal is to 1) increase the hydrophilicity of the presented compounds along with their molecular weight, 2) inactivate their biological effects and 3) facilitate their efflux from the cells, subsequently followed by excretion into bile or urine1. The metabolic enzymes in charge of this process are traditionally organized into two separate categories; phase I (oxidation, reduction, or hydrolysis) and phase II (conjugation) enzymes1,2. During phase I, polar groups are added to the molecules through oxidation, reduction, and hydrolysis, mediated generally through cytochrome p450 enzymes. Phase II …show more content…
et al. Identification of aspartic acid and histidine residues mediating the reaction mechanism and the substrate specificity of the human UDP-glucuronosyltransferases 1A. The Journal of biological chemistry 282, 36514-36524, doi:10.1074/jbc.M703107200 …show more content…
I., Bowalgaha, K., Finel, M. & Miners, J. O. Influence of N-terminal domain histidine and proline residues on the substrate selectivities of human UDP-glucuronosyltransferase 1A1, 1A6, 1A9, 2B7, and 2B10. Drug metabolism and disposition: the biological fate of chemicals 37, 1948-1955, doi:10.1124/dmd.109.028225 (2009).
6 Ghosh, C. et al. Expression and functional relevance of UGT1A4 in a cohort of human drug-resistant epileptic brains. Epilepsia 54, 1562-1570, doi:10.1111/epi.12318 (2013).
7 Stingl, J. C., Bartels, H., Viviani, R., Lehmann, M. L. & Brockmoller, J. Relevance of UDP-glucuronosyltransferase polymorphisms for drug dosing: A quantitative systematic review. Pharmacology & therapeutics 141, 92-116, doi:10.1016/j.pharmthera.2013.09.002 (2014).
8 Rowland, A. et al. In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction. Drug metabolism and disposition: the biological fate of chemicals 34, 1055-1062, doi:10.1124/dmd.106.009340 (2006).
9 Gidal, B. E., Sheth, R., Parnell, J., Maloney, K. & Sale, M. Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Epilepsy research 57, 85-93, doi:10.1016/j.eplepsyres.2003.09.008