UDP-glucuronosyltransferases 1A6 and 1A10 catalyze reduced menadione glucuronidation
| Autor: | Tomokazu Ohnuma, Takahito Nishiyama, Kenichiro Ogura, Takehiko Kishi, Yuu Inoue, Akira Hiratsuka |
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| Rok vydání: | 2008 |
| Předmět: |
UGT1A6
Biophysics Glucuronidation Oxidative phosphorylation Biochemistry Catalysis chemistry.chemical_compound Glucuronic Acid Menadione Microsomes NAD(P)H Dehydrogenase (Quinone) Animals Humans Glucuronosyltransferase Molecular Biology Cells Cultured Vitamin K 3 Cell Biology Metabolism Glucuronic acid Recombinant Proteins Jejunum Liver chemistry Menadiol Inactivation Metabolic NAD+ kinase |
| Zdroj: | Biochemical and Biophysical Research Communications. 371:247-250 |
| ISSN: | 0006-291X |
| Popis: | Menadione (2-methyl-1,4-naphthoquine), also known as vitamin K3, has been widely used as a model compound in the field of oxidative stress-related research. The metabolism of menadione has been studied, and it is known that menadione undergoes a two-electron reduction by NAD(P)H:Quinone oxidoreductase 1 (NQO1) after which the reduced form of menadione (2-methyl-1,4-naphthalenediol, menadiol) is glucuronidated and excreted in urine. To investigate which human UDP-glucuronosyltransferase (UGT) isoforms participate in the glucuronidation of menadiol reduced by NQO1 from menadione, we first constructed heterologously expressed NQO1 in Sf9 cells and tested the menadiol glucuronidating activity of 16 human recombinant UGT isoforms. Of the 16 UGT isoforms, UGTs 1A6, 1A7, 1A8, 1A9, and 1A10 catalyzed menadiol glucuronidation, and, of these, UGTs 1A6 and 1A10 catalyzed menadiol glucuronidation at much higher rates than the other UGTs. Menadiol was regioselectively glucuronidated in the manner of 4-position > 1-position by UGTs 1A7, 1A8, 1A9, and 1A10. In contrast to these UGTs, only UGT1A6 exhibited 1-menadiol-preferential glucuronidating activity. The results suggest possible detoxification pathways for quinones via NQO1 reduction followed by UGT glucuronidation. |
| Databáze: | OpenAIRE |
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