UGTs have been divided into two families: UGT1 and UGT2, based on similarities between their amino acid sequences and gene organization. Hepatic UGTactivity in the microminipig compared to those in humans and other experimental animals. Estradiol-3-glucuronidation activity is higher in the microminipig than in humans and other animals, serotonin glucuronide formation activity is 20-55fold higher in mouse and rat liver microsomes than in microsomes from the other animals. Glucuronidation activities are 2fold higher in microminipig microsomes than in human, dog or monkey microsomes, overview
UGTs have been divided into two families: UGT1 and UGT2, based on similarities between their amino acid sequences and gene organization. Hepatic UGTactivity in the microminipig compared to those in humans and other experimental animals. Estradiol-3-glucuronidation activity is higher in the microminipig than in humans and other animals, serotonin glucuronide formation activity is 20-55fold higher in mouse and rat liver microsomes than in microsomes from the other animals. Glucuronidation activities are 2fold higher in microminipig microsomes than in human, dog or monkey microsomes, overview
UGTs have been divided into two families: UGT1 and UGT2, based on similarities between their amino acid sequences and gene organization. Hepatic UGTactivity in the microminipig compared to those in humans and other experimental animals. Estradiol-3-glucuronidation activity is higher in the microminipig than in humans and other animals, serotonin glucuronide formation activity is 20-55fold higher in mouse and rat liver microsomes than in microsomes from the other animals. Glucuronidation activities are 2fold higher in microminipig microsomes than in human, dog or monkey microsomes, overview
UGTs have been divided into two families: UGT1 and UGT2, based on similarities between their amino acid sequences and gene organization. Hepatic UGTactivity in the microminipig compared to those in humans and other experimental animals. Estradiol-3-glucuronidation activity is higher in the microminipig than in humans and other animals, serotonin glucuronide formation activity is 20-55fold higher in mouse and rat liver microsomes than in microsomes from the other animals. Glucuronidation activities are 2fold higher in microminipig microsomes than in human, dog or monkey microsomes, overview
UGTs have been divided into two families: UGT1 and UGT2, based on similarities between their amino acid sequences and gene organization. Hepatic UGTactivity in the microminipig compared to those in humans and other experimental animals. Estradiol-3-glucuronidation activity is higher in the microminipig than in humans and other animals, serotonin glucuronide formation activity is 20-55fold higher in mouse and rat liver microsomes than in microsomes from the other animals. Glucuronidation activities are 2fold higher in microminipig microsomes than in human, dog or monkey microsomes, overview
UGTs have been divided into two families: UGT1 and UGT2, based on similarities between their amino acid sequences and gene organization. Hepatic UGTactivity in the microminipig compared to those in humans and other experimental animals. Estradiol-3-glucuronidation activity is higher in the microminipig than in humans and other animals, serotonin glucuronide formation activity is 20-55fold higher in mouse and rat liver microsomes than in microsomes from the other animals. Glucuronidation activities are 2fold higher in microminipig microsomes than in human, dog or monkey microsomes, overview
IPUT1 belongs to a glycosyltransferase family that transfers sugars with a retaining mechanism resulting in alpha-linked sugars, consistent with the alpha conformation of the GlcA in glycosyl inositol phosphorylceramides (GIPCs)
IPUT1 belongs to a glycosyltransferase family that transfers sugars with a retaining mechanism resulting in alpha-linked sugars, consistent with the alpha conformation of the GlcA in glycosyl inositol phosphorylceramides (GIPCs)
UGT3A enzymes are functionally distinct from other UGT subfamilies (which use UDP-glucuronic acid as a cosubstrate) due to their utilization of alternative cosubstrates (UDP-N-acetylglucosamine for UGT3A1, and UDP-glucose and UDP-xylose for UGT3A2). The overall expression level in tissue is higher for isozyme UGT3A2 compared to isozyme UGT3A1
due to frequent haplotype blocks within the UGT1 gene locus, the Gilbert variant UGT1A1*28 is often associated with polymorphisms of UGT1A6. Rare hyperserotoninemia mimicking carcinoid syndrome may be due to the linked dual polymorphisms of UGT1A1 and UGT1A6
life saving function of bilirubin glucuronidation is obvious from death of children carrying the UGT1A1-deficient Crigler-Najjar syndrome, type 1 genotype. Excessive serum bilirubin levels leading to brain damage in neonates are prevented by induction of UGT1A1, the sole enzyme conjugating bilirubin. Reduced L-thyroxine (T4)glucuronidation in carriers of the Gilbert genotype UGT1A1*28 substantiates a role for UGT1A1 in T4 glucuronidation. Due to frequent haplotype blocks within the UGT1 gene locus, the Gilbert variant UGT1A1*28 is often associated with polymorphisms of UGT1A6. Rare hyperserotoninemia mimicking carcinoid syndrome may be due to the linked dual polymorphisms of UGT1A1 and UGT1A6
overexpression or silencing of IPUT1 in Nicotiana benthamiana results in an increase or a decrease, respectively, in IPC glucuronosyltransferase activity in vitro. Plants in which IPUT1 is silenced accumulate IPC, the immediate precursor, as well as ceramides and glucosylceramides. Plants overexpressing IPUT1 show an increased content of GIPCs. Mutations in IPUT1 are not transmitted through pollen, indicating that these sphingolipids are essential in plants
UGT3A1-overexpressing microsomes also demonstrates activity against 8-hydroxy-benzo[a]pyrene (8-OH-BaP) and BaP-9,10-diol. Two GlcNAc conjugates are observed for BaP-9,10-diol, likely representing N-acetylglucosaminides at the 9- and 10-diol positions. No detectable glycosylation activity for any other PAH tested is seen with UGT3A1-overexpressing microsomes
UGT3A2-overexpressing microsomes show UGT3A2 activity against all of the PAHs tested using UDP-Glc as cosubstrate. In addition to 1-OH-pyrene, UGT3A2-overexpressing microsomes exhibit high activity against the simple PAHs (1-OH-BaP, 3-OH-BaP, 7-OH-BaP, and 9-OH-BaP) to form glucoside metabolites
feedback loops between endobiotic UGT substrates and their transcription factors suggest an important role of their glucuronidation in evolution. AhR- and Nrf2-binding domains, termed XRE (xenobiotic responsive element) and ARE (antioxidant responsive element), respectively, are identified in the regulatory region of UGT1A1 and UGT1A6. The neurotransmitter serotonin is also solely glucuronidated by the human UGT1A6, which is highly expressed in the stomach and intestine. Serotonin exhibits a variety of functions in the gastrointestinal tract including gastrointestinal motility, mucosal growth/maintenance and intestinal inflammation
morphine glucuronidation and glucosidation represent complementary metabolic pathways that are both catalyzed by UDP-glucuronosyltransferase 2B7. Glucuronidation is the dominant metabolic pathway because the binding affinity of UDP-glucuronic acid to UGT2B7 is higher than that of UDPglucose. Morphine-3-beta-D-glucuronide and morphine-6-beta-D-glucuronide are the major metabolites of morphine in humans
isoform UGT1A1 is involved in glucuronidation´of the main warfarin metabolites, including Rac-6- and 7-hydroxywarfarin and their R- and S-enantiomers in the liver
oxidative stress induces significant deleterious changes in astrocyte morphology, decreases cell viability and inhibits catalytic function of UDP-glucuronosyltransferases as a result of protein oxidation. Alternatively, in the surviving impaired astrocytes, oxidative conditions induces a significant overactivity and overexpression of xenobiotic detoxification enzymes, as adaptive response. These effects are significantly prevented by the presence of melatonin, reflected further on the glucuronidation activity and transcriptional regulation of both UGT1A6 and UGT1A7. Both catalytic properties of UDP-glucuronosyltransferases and the expression of UGT1A6, UGT1A7, NQO1 and NADPH:cytochrome P450 reductase in rat astrocytes are greatly influenced by the pro-oxidative environment
human UDP-glucuronosyltransferases are major phase II enzymes in the drug metabolism system, they also have a role in clearance and homeostasis of endogenous substrates, UGTs are often involved in detoxification of endobiotic CYP metabolites. Species- and tissue/cell-dependent regulation of UGT expression by ligand-activated transcription factors is often involved in endobiotic homeostasis. All UGT1 family members appear to be controlled by the AhR transcription factor. Bilirubin and 20-hydroxyeicosatetraenoic acid act as activators of transcription factors that regulate UGT expression, and are involved in important feedback loops
human UDP-glucuronosyltransferases are major phase II enzymes in the drug metabolism system, they also have a role in clearance and homeostasis of endogenous substrates, UGTs are often involved in detoxification of endobiotic CYP metabolites. Species- and tissue/cell-dependent regulation of UGT expression by ligand-activated transcription factors is often involved in endobiotic homeostasis. All UGT1 family members appear to be controlled by the AhR transcription factor. Bilirubin and 20-hydroxyeicosatetraenoic acid act as activators of transcription factors that regulate UGT expression, and are involved in important feedback loops, proposed feedback loop between bilirubin, AhR and AhR-controlled UGT1A1. UGT1A1 is the sole enzyme conjugating bilirubin. AhR- and Nrf2-binding domains, termed XRE (xenobiotic responsive element) and ARE (antioxidant responsive element), respectively, are identified in the regulatory region of UGT1A1 and UGT1A6
human UDP-glucuronosyltransferases are major phase II enzymes in the drug metabolism system, they also have a role in clearance and homeostasis of endogenous substrates, UGTs are often involved in detoxification of endobiotic CYP metabolites. Species- and tissue/cell-dependent regulation of UGT expression by ligand-activated transcription factors is often involved in endobiotic homeostasis. All UGT1 family members appear to be controlled by the AhR transcription factor. Bilirubin and 20-hydroxyeicosatetraenoic acid act as activators of transcription factors that regulate UGT expression, and are involved in important feedback loops. In the intestine, L-thyroxine is conjugated by UGT1A8 and UGT1A10 suggesting first-pass metabolism of oral L-thyronine, although UGT1A1 and UGT1A3 are the major UGTs glucuronidating T4 at the hydroxyl and carboxyl groups, respectively
human UDP-glucuronosyltransferases are major phase II enzymes in the drug metabolism system, they also have a role in clearance and homeostasis of endogenous substrates, UGTs are often involved in detoxification of endobiotic CYP metabolites. Species- and tissue/cell-dependent regulation of UGT expression by ligand-activated transcription factors is often involved in endobiotic homeostasis. All UGT1 family members appear to be controlled by the AhR transcription factor. Bilirubin and 20-hydroxyeicosatetraenoic acid act as activators of transcription factors that regulate UGT expression, and are involved in important feedback loops. The family 2 member UGT2B7 is regulated by Nrf2, but not by the AhR. UGT1A9- and UGT2B7-mediated detoxification of 20-hydroxyeicosatetraenoic acid to prevent hypertension. UGT1A9 and UGT2B7 appear to be major UGT enzymes responsible for 20-hydroxyeicosatetraenoic acid and leukotriene B4 glucuronidation
human UDP-glucuronosyltransferases are major phase II enzymes in the drug metabolism system, they also have a role in clearance and homeostasis of endogenous substrates, UGTs are often involved in detoxification of endobiotic CYP metabolites. Species- and tissue/cell-dependent regulation of UGT expression by ligand-activated transcription factors is often involved in endobiotic homeostasis. All UGT1 family members appear to be controlled by the AhR transcription factor. Bilirubin and 20-hydroxyeicosatetraenoic acid act as activators of transcription factors that regulate UGT expression, and are involved in important feedback loops. UGT1A9- and UGT2B7-mediated detoxification of 20-hydroxyeicosatetraenoic acid to prevent hypertension. UGT1A9 and UGT2B7 appear to be major UGT enzymes responsible for 20-hydroxyeicosatetraenoic acid and leukotriene B4 glucuronidation
human UDP-glucuronosyltransferases are major phase II enzymes in the drug metabolism system, they also have a role in clearance and homeostasis of endogenous substrates, UGTs are often involved in detoxification of endobiotic CYP metabolites. Species- and tissue/cell-dependent regulation of UGT expression by ligand-activated transcription factors is often involved in endobiotic homeostasis. All UGT1 family members appear to be controlled by the AhR transcription factor. Bilirubin and 20-hydroxyeicosatetraenoic acid act as activators of transcription factors that regulate UGT expression, and are involved in important feedback loops. UGT2B28 is involved in estradiol and testosterone glucuronidation in a variety of tissues including breast cells
human UDP-glucuronosyltransferases are major phase II enzymes in the drug metabolism system, they also have a role in clearance and homeostasis of endogenous substrates. Species- and tissue/cell-dependent regulation of UGT expression by ligand-activated transcription factors is often involved in endobiotic homeostasis. All UGT1 family members appear to be controlled by the AhR transcription factor. Bilirubin and 20-hydroxyeicosatetraenoic acid act as activators of transcription factors that regulate UGT expression, and are involved in important feedback loops
metabolic function of UGTs can be severely influenced by hepatocellular carcinoma, analysis of alteration on the metabolism of UGTs specific substrates, translational and transcriptional activity of UGTs in hepatitis B virus-positive hepatocellular carcinoma patients, overview. In the tumor human liver microsomes, either Vmax or the clearance rates of UGT1A, UGT1A1, UGT1A4, UGT1A9 and UGT2B7 are significant lower than those of in the adjacent normal human liver microsomes. Protein and gene expressions of these isoforms are decreased in most of tumor tissues compared to the adjacent healthy tissues
UDP-glucuronosyltransferase (UGT) enzymes are critical for regulating nutrients, hormones, and endobiotics, as well as for detoxifying xenobiotics. Ugt1a proteins are present and active in preimplantation murine embryos and point to a potential role for these proteins in implantation and early embryonic and fetal development.
UGT1A9 and 2B7 are the main contributors to regioselective glucuronidation of gingerols in the liver, isozyme UGT12B7 is primarily responsible for 4'-O-glucuronidation of gingerols in the liver
UGT1A9 and 2B7 are the main contributors to regioselective glucuronidation of gingerols in the liver, isozyme UGT1A9 is primarily responsible for 5-O-glucuronidation of gingerols in the liver
UGT1A9 and 2B7 are the main contributors to regioselective glucuronidation of gingerols in the liver, isozyme UGT2B7 is primarily responsible for 4'-O-glucuronidation of gingerols in the liver
polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens and are a primary risk factor for the development of lung and other aerodigestive tract cancers in smokers. The detoxification of PAHs by glucuronidation is well-characterized for the UDP-glycosyltransferase (UGT) 1A, 2A, and 2B subfamilies
polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens and are a primary risk factor for the development of lung and other aerodigestive tract cancers in smokers. The detoxification of PAHs by glucuronidation is well-characterized for the UDP-glycosyltransferase (UGT) 1A, 2A, and 2B subfamilies. UGT3A2 is highly active against PAHs with either UDP-glucose or UDP-xylose as a cosubstrate: UGT3A2 plays an important role in the detoxification of PAHs in aerodigestive tract tissues, and that there may be cosubstrate-dependent differences in the detoxification of PAHs by UGT3A2
the uridine diphosphate glucuronosyltransferases (UGTs) catalyze glucuronidation to facilitate systemic and local clearance of numerous chemicals and drugs
UDP-glucuronosyltransferase (UGT) enzymes are critical for regulating nutrients, hormones, and endobiotics, as well as for detoxifying xenobiotics. Ugt1a proteins are present and active in preimplantation murine embryos and point to a potential role for these proteins in implantation and early embryonic and fetal development.