Bioconversion by functional P450 1A9 and P450 1C1 of Anguilla japonica

Uno, Tomohide; Okamoto, Sota; Masuda, Shinya; Imaishi, Hiromasa; Nakamura, Masahiko; Kanamaru, Kengo; Yamagata, Hiroshi; El-kady, Mohamed A. H.; Kaminishi, Yoshio; Itakura, Takao

doi:10.1016/j.cbpc.2007.11.004

Cited by 10 publications

(9 citation statements)

References 37 publications

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“…Using these preparations, we found that CYP1A and CYP1C1 have the highest rate of E 2 metabolism, followed by more modest E 2 metabolism by CYP1C2. The dominant metabolite formed was 2-OHE 2 , similar to studies seen in other fish (Uno et al 2008) and humans (Lee et al 2003). Similar to human E 2 metabolism by CYP1B1 (Lee et al 2003), the ratio of 4-OHE 2 to 2-OHE 2 was highest in zebrafish CYP1B1, yet the overall rates of metabolism by zebrafish CYP1B1 were lower than expected.…”

Section: Cyp1b1 (Jansson Et Al 2000)supporting

confidence: 77%

“…2-OHE 2 was the predominant metabolite formed in both zebrafish (this study) and mammalian studies (Lee et al 2003), and the 4-OHE 2 metabolite was produced to a much lower extent in both groups. In addition, Japanese eel CYP1A9 (one of two CYP1As in this species) also predominantly formed 2-OHE 2 (Uno et al 2008), though at a lower rate than seen here, possibly due to an 8 h reaction time in that study.…”

Section: Cyp1b1 (Jansson Et Al 2000)contrasting

confidence: 51%

“…The only reported E 2 metabolism by purified fish CYPs has been from Japanese eel showing 2-OH activity by CYP1A9 but not by CYP1C1; however, neither CYP produced 4-OHE 2 metabolites (Uno et al 2008). Since E 2 metabolism predominantly occurs in the liver, and the dominant metabolic products are 2-OHE 2 with smaller amounts of 4-OHE 2 for both mammals and fish, similar CYP families could be responsible for E 2 metabolism in mammalian and non-mammalian vertebrates.…”

Section: Introductionmentioning

confidence: 99%

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Cytochrome P450-mediated 17β-estradiol metabolism in zebrafish (Danio rerio)

Scornaienchi

Thornton²,

Willett³

et al. 2010

Journal of Endocrinology

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Cytochrome P4501 (CYP1) and CYP3A proteins are primarily responsible for the metabolism of 17b-estradiol (E 2 ) in mammals. We have cloned and heterologously expressed CYP1A, CYP1B1, CYP1C1, CYP1C2, CYP1D1, and CYP3A65 from zebrafish (Danio rerio) to determine the CYP-mediated metabolism of E 2 in a non-mammalian species. Constructs of each CYP cDNA were created using a leader sequence from the bacterial ompA gene to allow appropriate expression in Escherichia coli without 5 0 modification of the gene. Membrane vesicles were purified, and functional CYP protein was verified using carbon monoxide difference spectra and fluorescent catalytic assays with the substrates 7-ethoxyresorufin and 7-benzyloxy-4-(trifluoromethyl)-coumarin. Rates of in vitro E 2 metabolism into 4-hydroxyE 2 (4-OHE 2 ), 2-hydroxyE 2 (2-OHE 2 ), and 16a-hydroxyE 1 (16a-OHE 1 ) metabolites were determined by gas chromatography/mass spectrometry. The 2-OHE 2 metabolite was produced by all CYPs tested, while 4-OHE 2 was only detected following incubation with CYP1A, CYP1B1, CYP1C1, and CYP1C2. The 16a-OHE 1 metabolite was only produced by CYP1A. The highest rates of E 2 metabolism were from CYP1A and CYP1C1, followed by CYP1C2. CYP1B1, CYP1D1, and CYP3A65 had low rates of E 2 metabolism. E 2 metabolism by zebrafish CYP1A, CYP1C1, and CYP1C2 produced similar ratios of 4-OHE 2 to 2-OHE 2 as previous studies with mammalian CYP1As. CYP1B1 formed the highest ratio of 4-OHE 2 to 2-OHE 2 metabolites. Contrary to mammals, these results suggest that fish CYP1A and CYP1C proteins are primarily responsible for E 2 metabolism, with only minor contributions from CYP3A65 and CYP1B1. Similar to mammals, 2-OHE 2 is the predominant metabolite from CYP-mediated E 2 metabolism in fish, suggesting that all vertebrate species produce the same major E 2 metabolite.

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Section: Cyp1b1 (Jansson Et Al 2000)supporting

confidence: 77%

Section: Cyp1b1 (Jansson Et Al 2000)contrasting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

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Cytochrome P450-mediated 17β-estradiol metabolism in zebrafish (Danio rerio)

Scornaienchi

Thornton²,

Willett³

et al. 2010

Journal of Endocrinology

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show abstract

“…This is especially true for progesterone, which does not contain a hydroxyl group and therefore requires phase I metabolism (hydroxylation or keto reduction) in order to undergo conjugation and elimination. Studies in fish with 17-␤-estradiol, progesterone and testosterone show that steroid catabolism through hydroxylation is mainly carried out by microsomal P450s that are normally expressed in liver [9][10][11][12][13][14][15][16][17][18]. This is similar to findings with mammalian species, which have been studied more extensively [5,19].…”

Section: Cytochrome P450-dependent Hydroxylationsupporting

confidence: 72%

Steroid catabolism in marine and freshwater fish

James

2011

The Journal of Steroid Biochemistry and Molecular Biology

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“…Previously, we demonstrated that two P450 proteins (CYP1A9 and CYP1C1) from Japanese eel (Anguilla japonica) metabolized 7-ethoxycoumarin, phenyl urea herbicides, a flavanone, and the drug phenacetin in bioconversion experiments using whole E.coli cells (Uno et al 2008a). However, there is no data for the hydroxylation activities of these proteins towards their substrates using E.coli membrane fractions because we could not obtain a membrane fraction from Escherichia coli cells.…”

Section: Introductionmentioning

confidence: 96%