Glucuronosyltransferase

Publication Title: 
Nature

The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30?years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4?years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer.

Author(s): 
Tian, Xiao
Azpurua, Jorge
Hine, Christopher
Vaidya, Amita
Myakishev-Rempel, Max
Ablaeva, Julia
Mao, Zhiyong
Nevo, Eviatar
Gorbunova, Vera
Seluanov, Andrei
Publication Title: 
Nature

The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30?years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4?years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer.

Author(s): 
Tian, Xiao
Azpurua, Jorge
Hine, Christopher
Vaidya, Amita
Myakishev-Rempel, Max
Ablaeva, Julia
Mao, Zhiyong
Nevo, Eviatar
Gorbunova, Vera
Seluanov, Andrei
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

The aim of this study was to elucidate the metabolic pathways for dihydroartemisinin (DHA), the active metabolite of the artemisinin derivative artesunate (ARTS). Urine was collected from 17 Vietnamese adults with falciparum malaria who had received 120 mg of ARTS i.v., and metabolites were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Human liver microsomes were incubated with [12-(3)H]DHA and cofactors for either glucuronidation or cytochrome P450-catalyzed oxidation. Human liver cytosol was incubated with cofactor for sulfation.

Author(s): 
Ilett, Kenneth F.
Ethell, Brian T.
Maggs, James L.
Davis, Timothy M. E.
Batty, Kevin T.
Burchell, Brian
Binh, Tran Quang
Thu, Le Thi Anh
Hung, Nguyen Canh
Pirmohamed, Munir
Park, B. Kevin
Edwards, Geoffrey
Publication Title: 
European Journal of Clinical Pharmacology

OBJECTIVE: UDP-glucuronosyltransferases (UGTs) UGT1A9 and UGT2B7 are involved in the metabolism of antimalarial dihydroartemisinin and antiretroviral zidovudine. Our aim was to analyze the prevalence of UGT1A9 (chromosome 2) and UGT2B7 (chromosome 4) nonsynonymous single nucleotide polymorphisms (SNPs) in West African (WA), Papua New Guinean (PNG), and North American (NA) populations.

Author(s): 
Mehlotra, Rajeev K.
Bockarie, Moses J.
Zimmerman, Peter A.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

CYP2A6, CYP2B6, and UGT1A9 genetic polymorphisms and treatment response after a three-day course of artesunate-mefloquine was investigated in 71 Burmese patients with uncomplicated Plasmodium falciparum malaria. Results provide evidence for the possible link between CYP2A6 and CYP2B6 polymorphisms and plasma concentrations of artesunate/dihydroartemisinin and treatment response.

Author(s): 
Phompradit, Papichaya
Muhamad, Poonuch
Cheoymang, Anurak
Na-Bangchang, Kesara
Publication Title: 
Molecules (Basel, Switzerland)

Gossypol, the polyphenolic constituent isolated from cottonseeds, has been used as a male antifertility drug for a long time, and has been demonstrated to exhibit excellent anti-tumor activity towards multiple cancer types. The toxic effects of gossypol limit its clinical utilization, and enzyme inhibition is an important facet of this. In the present study, in vitro human liver microsomal incubation system supplemented with UDPGA was used to investigate the inhibition of gossypol towards UGT1A1, 1A9 and 2B7-mediated metabolism of xenobiotics and endogenous substances.

Author(s): 
Zhang, Yong-sheng
Yuan, Jun
Fang, Zhong-Ze
Tu, Yan-yang
Hu, Cui-Min
Li, Gan
Wang, Liang
Deng, Jian-Ping
Yao, Jia-Jiu
Li, Hai-Rong
Publication Title: 
Molecules (Basel, Switzerland)

Celastrol, a quinone methide triterpene isolated from Tripterygium wilfordii Hook F., has various biochemical and pharmacological activities, and is now being developed as a promising anti-tumor agent. Inhibitory activity of compounds towards UDP-glucuronosyltransferase (UGT) is an important cause of clinical drug-drug interactions and herb-drug interactions. The aim of the present study is to investigate the inhibition of celastrol towards two important UDP-glucuronosyltransferase (UGT) isoforms UGT1A6 and UGT2B7.

Author(s): 
Zhang, Yong-sheng
Tu, Yan-yang
Gao, Xing-Chun
Yuan, Jun
Li, Gang
Wang, Liang
Deng, Jian-Ping
Wang, Qi
Ma, Ru-Meng
Publication Title: 
Die Pharmazie

The aim of the present study was to investigate the inhibitory potential of glimepiride towards important UDP-glucuronosyltransferase (UGT) isoforms in human liver, which play a key role in the elimination of drugs. The recombinant UGT enzymes were used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 microM of glimepiride inhibited UGT1A1, UGT1A3, UGT1A6, UGT1A9, UGT2B7 and UGT2B15 by 54.7%, 43.1%, 100%, 70.5%, 32.7 and 37.2%, respectively.

Author(s): 
Fu, Jian-Fang
Ren, Qin-You
Zhang, Nan-Yan
Gao, Bin
Tu, Yan-yang
Fu, Guo-Qiang
Li, Dao-Hai
Zhang, Yong-sheng
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

UDP-glucuronosyltransferase 2B7 (UGT2B7) is involved in the glucuronidation of a wide array of clinically important drugs and endogenous compounds in humans. The aim of this study was to identify an isoform-selective probe substrate that could be used to investigate genetic and environmental influences on glucuronidation mediated by UGT2B7. Three potential probe substrates [3'-azido-3'-deoxythymidine (AZT), morphine, and codeine], were evaluated using recombinant UGTs and human liver microsomes (HLMs; n = 54).

Author(s): 
Court, Michael H.
Krishnaswamy, Soundarajan
Hao, Qin
Duan, Su X.
Patten, Christopher J.
von Moltke, Lisa L.
Greenblatt, David J.
Publication Title: 
Plant Physiology

Alfalfa (Medicago sativa) and Arabidopsis were used as model systems to examine molecular mechanisms underlying developmental effects of a microsomal UDP-glucuronosyltransferase-encoding gene from pea (Pisum sativum; PsUGT1). Alfalfa expressing PsUGT1 antisense mRNA under the control of the cauliflower mosaic virus (CaMV) 35S promoter exhibited delayed root emergence, reduced root growth, and increased lateral root development. The timing of root emergence in wild-type and antisense plants was correlated with the transient accumulation of auxin at the site of root emergence.

Author(s): 
Woo, Ho-Hyung
Faull, Kym F.
Hirsch, Ann M.
Hawes, Martha C.

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