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首页> 外文期刊>Comparative biochemistry and physiology, Part C. Pharmacology, toxicology and endocrinology: An international journal >Catalytic properties of CYP1A isoforms in the liver of an agnathan (Lampetra fluviatilis) and two species of teleost (Pleuronectes flesus, Anguilla anguilla)
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Catalytic properties of CYP1A isoforms in the liver of an agnathan (Lampetra fluviatilis) and two species of teleost (Pleuronectes flesus, Anguilla anguilla)

机译：agnathan（flupetiltilis）和两种硬骨鱼（Pleuronectes flesus，Anguilla anguilla）肝脏中CYP1A亚型的催化特性

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The catalytic activity of CYP1A isoforms and the effect of mammalian CYP1A-specific inhibitors in liver S9 fractions were studied in an agnathan (River lamprey, Lampetra fluviatilis, 30-33 cm) and in two species of teleost fish (European flounder. Pleuronectes flesus, 11-18 cm and common eel, Anguilla anguilla, 31-45 cm). Ethoxyresorufin O-deethylation (EROD), caffeine N-demethylation/C-oxidation and phenacetin O-deethylation (POD) activity increased 3-4-fold in flounders and 17-46-fold in eels, 5 days after fish were injected (i.p.) with 100 mg kg(-1) benzo(a)pyrene (B[a]P). In lampreys, basal EROD activity was very low and no increase in activity was observed following exposure to B[a]P. While the apparent Michaelis constant (K-m) for each assay showed only small changes after B[a]P injection, maximum-reaction velocity (V-max) values increased by up to 19- acid 84-fold for EROD activity, 4- and 35-fold for caffeine-related metabolism and 4- and 19-fold for POD activity in flounders and eels, respectively. The mammalian CYP1A2 inhibitor furafylline (50 mu M-1 mM) reduced activity in the EROD, caffeine and POD assays to 65, 21 and 20% of control values in flounders and to 85, 10 and 5% of control values in eels, respectively. By contrast, low concentrations (0.025-0.050 mu M) of the mammalian CYP1A1 inhibitor ellipticine completely abolished EROD activity, but had no effect (up to 1 mM) on caffeine metabolism or POD activity in either species. While the inhibitor studies strongly suggest that two separate enzymes are present in flounders and eels, the monophasic Michaelis-Menten kinetics obtained in all the assays imply that only a single CYP1A protein is present that has substrate and inhibitor specificities characteristic bf both mammalian CYP1A1 and CYP1A2 isoforms. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 33]
机译：在agnathan（River Lamprey，Lampetra fluviatilis，30-33 cm）和两种硬骨鱼（欧洲比目鱼.Pleuronectes flesus， 11-18厘米，以及普通鳗鱼，安圭拉鳗鱼（31-45厘米）。注入鱼5天后，比目鱼的乙氧异黄素O-去乙基化（EROD），咖啡因N-去甲基/ C-氧化和非那西丁O-去乙基化（POD）活性增加了3-4倍，鳗鱼增加了17-46倍（ip ）与100毫克kg（-1）苯并（a）（（B [a] P）。在七lamp鳗中，基础EROD活性非常低，暴露于B [a] P后未观察到活性增加。虽然每次分析的表观米氏常数（Km）仅显示出B [a] P注射后的微小变化，但最大反应速度（V-max）值对于EROD活性，4-和4最多增加了19-酸84倍。比目鱼和鳗鱼中与咖啡因有关的代谢分别为35倍和POD活性的4倍和19倍。哺乳动物CYP1A2抑制剂呋喃茶碱（50μM-1 mM）在比目鱼中EROD，咖啡因和POD分析中的活性分别降低至对照值的65％，21％和20％，以及鳗鱼中对照值的85％，10％和5％ 。相比之下，低浓度（0.025-0.050μM）的哺乳动物CYP1A1抑制剂玫瑰树碱完全消除了EROD活性，但对两种物种中的咖啡因代谢或POD活性均无影响（最高1 mM）。尽管抑制剂的研究强烈提示在比目鱼和鳗鱼中存在两种独立的酶，但在所有测定中获得的单相Michaelis-Menten动力学暗示仅存在一种CYP1A蛋白，该蛋白具有哺乳动物CYP1A1和CYP1A2的底物和抑制剂特异性亚型。 （C）2000 Elsevier Science Inc.保留所有权利。 [参考：33]

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