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首页> 外文学位 >Cytochrome P450 enzymes in channel catfish, Ictalurus punctatus and metabolism of testosterone by catfish intestinal microsomes.
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Cytochrome P450 enzymes in channel catfish, Ictalurus punctatus and metabolism of testosterone by catfish intestinal microsomes.

机译：channel鱼肠道微粒体中通道channel鱼，小脚c鱼和睾丸激素代谢中的细胞色素P450酶。

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摘要

Intestinal cytochrome P450 provides the principal, initial source of biotransformation of ingested xenobiotics. In humans, an important cause of incomplete bioavailability is prehepatic metabolism in the GI tract, mainly by the CYP3A enzymes. The expression and properties of CYP proteins were examined along the intestine of channel catfish, Ictalurus punctatus, fed commercial chow or semi-purified diets. Benzo(a)pyrene hydroxylase activity was higher in proximal than distal intestine, and was stimulated by α-naphthoflavone, suggesting involvement of CYP3A. Polyclonal antibodies (IgG) generated against trout CYP3A27 reacted strongly with catfish intestinal microsomes, showing a band with MW of 59 kDa. In catfish fed with standard chow, the expression of this protein was much higher in the proximal segment than in the distal part. Testosterone 6β-hydroxylation activities were monitored as the catalytic indicator of CYP3A, which was higher in proximal than distal intestine. The 6β-hydroxylation activities in the two segments correlated with the amount of CYP3A. Similar results were obtained with progesterone as substrate. The amount of CYP3A and steroid-6β-hydroxylation activities were lower in both segments of intestine from fish fed purified diet compared with commercial chow, but with the same trend along intestine.; Incubation of catfish intestinal or hepatic microsomes with [4- 14C] testosterone resulted in three major metabolites: 6β-hydroxy testosterone, androstenedione and another metabolite. The formation of this unknown metabolite requires NADPH as cofactor. Comparison of the chromatographic behavior and MS of the unknown metabolite with that of authentic testosterone derivative suggested that this metabolite corresponds to 4-androsten-3α, 17β-diol. The ratio of testosterone 6β-hydroxylation/17-oxidation was significantly higher in proximal than distal intestine.; Testosterone 6β-hydroxylation was inhibited by specific mammalian CYP3A inhibitors, ketoconazole and erythromycin, and general P450 inhibitors, metyrapone and SKF-525A, but was not affected by α-naphthoflavone. Troleandomycin, a mammalian CYP3A inhibitor, had no effect on the testosterone metabolism by catfish intestinal microsomes up to 100 μM. Dietary pretreatment of catfish with rifampicin or pregnenolone-16α-carbonitrile (PCN) did not alter the CYP3A enzyme level in proximal and distal intestine. Distal intestine from fish treated with rifampicin for 2 weeks showed significantly higher testosterone 6β-hydroxylation and 3α-oxido-reduction activities than that from control fish.
机译：肠道细胞色素P450提供了摄入的异种生物的生物转化的主要初始来源。在人类中，生物利用度不完全的一个重要原因是胃肠道中的肝前代谢，主要是通过CYP3A酶。 CYP蛋白的表达和特性在along鱼，斜纹小腿大肠鱼，商业饲料或半纯饲料的肠道中进行检测。苯并（a）hydroxyl羟化酶活性在近端高于远端肠，并受到α-萘黄酮的刺激，提示CYP3A参与。针对鳟鱼CYP3A27产生的多克隆抗体（IgG）与cat鱼肠道微粒体发生强烈反应，显示出一条分子量为59 kDa的条带。在用标准饲料喂养的cat鱼中，该蛋白的表达在近端部分远高于远端部分。监测睾酮6β-羟基化活性作为CYP3A的催化指标，其在近端的肠内含量高于远端的肠内。两个片段中的6β-羟基化活性与CYP3A的量相关。以黄体酮为底物获得相似的结果。 CYP3A和甾体6β-羟化活性的含量在以纯饲料喂养的鱼的两个肠段均比市售的食物低，但沿肠的趋势相同。 4-鱼肠道或肝脏微粒体与[4- 14 C]睾丸酮一起孵育会产生三种主要代谢产物：6β-羟基睾丸酮，雄烯二酮和另一种代谢产物。这种未知代谢产物的形成需要NADPH作为辅因子。未知代谢物与真实睾丸激素衍生物的色谱行为和质谱比较表明，该代谢物对应于4-雄烯-3α，17β-二醇。睾丸中6β-羟基化/ 17-氧化的比率在近端比远端肠明显更高。特定的哺乳动物CYP3A抑制剂，酮康唑和红霉素以及一般的P450抑制剂，甲吡酮和SKF-525A抑制睾丸激素6β-羟基化，但不受α-萘黄酮的影响。 Troleandomycin是一种哺乳动物的CYP3A抑制剂，对on鱼肠道微粒体（最高100μM）的睾丸激素代谢没有影响。鱼的利福平或孕烯醇酮-16α-腈（PCN）饮食预处理不会改变近端和远端肠中CYP3A酶的水平。利福平处理2周的鱼的远处肠道的睾丸激素6β-羟基化和3α-氧化还原活性明显高于对照鱼。

著录项

  • 作者

    Lou, Zhen.;

  • 作者单位

    University of Florida.;

  • 授予单位 University of Florida.;
  • 学科 Health Sciences Toxicology.; Chemistry Biochemistry.; Biology Animal Physiology.; Agriculture Fisheries and Aquaculture.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 122 p.
  • 总页数 122
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学（毒理学）;生物化学;生理学;水产、渔业;
  • 关键词

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