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Uno Y Suzuki Y Wakaguri H Sakamoto Y Sano H Osada N Hashimoto K Sugano S Inoue I 《FEBS letters》2008,582(2):351-358
The liver, a major organ for drug metabolism, is physiologically similar between monkeys and humans. However, the paucity of identified genes has hampered a deep understanding of drug metabolism in monkeys. To provide such a genetic resource, 28655 expressed sequence tags (ESTs) were generated from a cynomolgus monkey liver full-length enriched cDNA library, which contained 23 unique ESTs homologous to human drug-metabolizing enzymes. Our comparative genomics approach identified nine lineage-specific candidate ESTs, including three drug-metabolizing enzymes, which could be important for understanding the physiological differences between monkeys and humans. 相似文献
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The Arabidopsis UDP‐glycosyltransferases UGT79B2 and UGT79B3, contribute to cold,salt and drought stress tolerance via modulating anthocyanin accumulation
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Pan Li Yan‐Jie Li Feng‐Ju Zhang Gui‐Zhi Zhang Xiao‐Yi Jiang Hui‐Min Yu Bing‐Kai Hou 《The Plant journal : for cell and molecular biology》2017,89(1):85-103
The plant family 1 UDP‐glycosyltransferases (UGTs) are the biggest GT family in plants, which are responsible for transferring sugar moieties onto a variety of small molecules, and control many metabolic processes; however, their physiological significance in planta is largely unknown. Here, we revealed that two Arabidopsis glycosyltransferase genes, UGT79B2 and UGT79B3, could be strongly induced by various abiotic stresses, including cold, salt and drought stresses. Overexpression of UGT79B2/B3 significantly enhanced plant tolerance to low temperatures as well as drought and salt stresses, whereas the ugt79b2/b3 double mutants generated by RNAi (RNA interference) and CRISPR‐Cas9 strategies were more susceptible to adverse conditions. Interestingly, the expression of UGT79B2 and UGT79B3 is directly controlled by CBF1 (CRT/DRE‐binding factor 1, also named DREB1B) in response to low temperatures. Furthermore, we identified the enzyme activities of UGT79B2/B3 in adding UDP‐rhamnose to cyanidin and cyanidin 3‐O‐glucoside. Ectopic expression of UGT79B2/B3 significantly increased the anthocyanin accumulation, and enhanced the antioxidant activity in coping with abiotic stresses, whereas the ugt79b2/b3 double mutants showed reduced anthocyanin levels. When overexpressing UGT79B2/B3 in tt18 (transparent testa 18), a mutant that cannot synthesize anthocyanins, both genes fail to improve plant adaptation to stress. Taken together, we demonstrate that UGT79B2 and UGT79B3, identified as anthocyanin rhamnosyltransferases, are regulated by CBF1 and confer abiotic stress tolerance via modulating anthocyanin accumulation. 相似文献
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Takeuchi T Tsutsumi O Nakamura N Ikezuki Y Takai Y Yano T Taketani Y 《Biochemical and biophysical research communications》2004,325(2):549-554
Gender difference in human bisphenol A (BPA) concentrations was revealed by determining serum BPA. We studied the serum concentrations and the metabolism of BPA in rats by an HPLC system. Rat serum BPA concentrations were significantly higher in males (24.9+/-7.38 ng/ml, P=0.026, n=10) than in females (8.27+/-3.11 ng/ml, n=10), as in humans. The resultant enzyme reaction products of BPA glucuronidation in the rat liver microsomes fraction were analyzed by an HPLC system. The ratio of BPA glucuronidation in the microsome reaction was significantly higher (P=0.015) in female than in male rats. The mRNA expression of UDP-glucuronosyltransferase 2B1 (UGT2B1), an isoform of UGT related to BPA glucuronidation, in the rat liver was analyzed by a real-time quantitative RT-PCR. The relative expression level of UGT2B1 mRNA was significantly higher (P<0.001) in female than in male rat livers. The gender difference in serum BPA concentrations may be explained by the difference in clearance based on the UGT activities. 相似文献
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Anthony T. Ginnetti Daniel V. Paone Shaun R. Stauffer Craig M. Potteiger Anthony W. Shaw James Deng James J. Mulhearn Diem N. Nguyen Carolyn Segerdell Juliana Anquandah Amy Calamari Gong Cheng Michael D. Leitl Annie Liang Eric Moore Jacqueline Panigel Mark Urban Jixin Wang Christopher S. Burgey 《Bioorganic & medicinal chemistry letters》2018,28(8):1392-1396
A second-generation small molecule P2X3 receptor antagonist has been developed. The lead optimization strategy to address shortcomings of the first-generation preclinical lead compound is described herein. These studies were directed towards the identification and amelioration of preclinical hepatobiliary findings, reducing potential for drug-drug interactions, and decreasing the projected human dose of the first-generation lead. 相似文献
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尿苷二磷酸葡萄糖醛酸转移酶(UDP-glucuronosyltransferase,UGT)家族是植物体内最大的糖基转移酶家族。编码合成UGT的基因属于UGT基因家族。UGT催化的糖基化反应广泛地存在于药用植物次生代谢物质的合成过程中。作为代谢通路中的下游修饰,供体分子在UGT的催化下,将糖基连接到受体分子上。这一过程往往会改变终产物的理化及生物学性质,最终影响其实际的利用价值及利用方式。本文综述分析了药用植物UGT家族基因挖掘分析、功能验证和生产应用等方面近年来的研究进展。 相似文献
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Yu Wang Liangliang Chen Yangyang Li Ming Yan Kequan Chen 《Bioscience, biotechnology, and biochemistry》2016,80(1):67-73
Stevioside and rebaudioside A are the chief diterpene glycosides present in the leaves of Stevia rebaudiana. Rebaudioside A imparts a desirable sweet taste, while stevioside produces a residual bitter aftertaste. Enzymatic synthesis of rebaudioside A from stevioside can increase the ratio of rebaudioside A to stevioside in steviol glycoside products, providing a conceivable strategy to improve the organoleptic properties of steviol glycoside products. Here, we demonstrate the efficient conversion of stevioside to rebaudioside A by coupling the activities of recombinant UDP-glucosyltransferase UGT76G1 from S. rebaudiana and sucrose synthase AtSUS1 from Arabidopsis thaliana. The conversion occurred via regeneration of UDP-glucose by AtSUS1. UDP was applicable as the initial material instead of UDP-glucose for UDP-glucose recycling. The amount of UDP could be greatly reduced in the reaction mixture. Rebaudioside A yield in 30?h with 2.4?mM stevioside, 7.2?mM sucrose, and 0.006?mM UDP was 78%. 相似文献
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The cotton bollworm Helicoverpa armigera and the tobacco budworm Heliothis virescens are closely related generalist insect herbivores and serious pest species on a number of economically important crop plants including cotton. Even though cotton is well defended by its major defensive compound gossypol, a toxic sesquiterpene dimer, larvae of both species are capable of developing on cotton plants. In spite of severe damage larvae cause on cotton plants, little is known about gossypol detoxification mechanisms in cotton-feeding insects. Here, we detected three monoglycosylated and up to five diglycosylated gossypol isomers in the feces of H. armigera and H. virescens larvae fed on gossypol-supplemented diet. Candidate UDP-glycosyltransferase (UGT) genes of H. armigera were selected by microarray studies and in silico analyses and were functionally expressed in insect cells. In enzymatic assays, we show that UGT41B3 and UGT40D1 are capable of glycosylating gossypol mainly to the diglycosylated gossypol isomer 5 that is characteristic for H. armigera and is absent in H. virescens feces. In conclusion, our results demonstrate that gossypol is partially metabolized by UGTs via glycosylation, which might be a crucial step in gossypol detoxification in generalist herbivores utilizing cotton as host plant. 相似文献
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