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Identification of a Single Nucleotide Polymorphism in Porcine Testis Cytochrome P450-c17 (CYP17) and Its Effect on Steroidogenesis

机译:猪睾丸细胞色素P450-c17(CYP17)单核苷酸多态性的鉴定及其对类固醇形成的影响

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Raising uncastrated male pigs could have significant economic benefits for pig production. Uncastrated male pigs can accumulate high levels of 16-androstene steroids, however, resulting in boar taint, which is highly objectionable to consumers. Cytochrome P450-c17 (CYP17) interacts with cytochrome b5 in the biosynthesis of the 16-androstene steroids and the sex steroids from pregnenolone. Amino acid substitutions in CYP17 could therefore affect the ability of this enzyme to catalyze the reactions leading to the production of androstenone and the sex steroids. In this study, we established a sensitive and flexible single-stranded conformational polymorphism technique capable of detecting a single nucleotide polymorphism. We then used this method to identify a substitution from T to A at nucleotide 1317 of CYP17, which caused a change in the amino acid sequence from Leu439 to His439. This mutation, however, did not alter the enzyme activity of CYP17 in the biosynthesis of androstenone or sex steroids. Other polymorphisms previously suggested for CYP17, which are vital for the functional interaction of CYP17 with CYB5 in human, were not observed. This study suggests that the synthesis of androstenone in pig testis is not directly affected by any polymorphisms in the coding region of the porcine CYP17 gene.
机译:饲养未cast割的雄性猪可以为养猪生产带来巨大的经济利益。未cast割的公猪会积聚高水平的16-雄甾烯类固醇,导致公猪异味,这对消费者非常不利。细胞色素P450-c17(CYP17)与细胞色素b5相互作用,可生物合成16-雄烯醇类固醇和孕烯醇酮的性类固醇。因此,CYP17中的氨基酸取代可能影响该酶催化导致雄烯酮和性类固醇生成的反应的能力。在这项研究中,我们建立了一种敏感而灵活的单链构象多态性技术,能够检测单核苷酸多态性。然后,我们使用此方法鉴定了CYP17核苷酸1317处T到A的取代,这导致了氨基酸序列从Leu439 变为His439 。然而,该突变在雄烯酮或性类固醇的生物合成中并未改变CYP17的酶活性。未观察到先前建议的CYP17的其他多态性,这些多态性对于CYP17与CYB5在人体内的功能相互作用至关重要。这项研究表明,猪睾丸中雄烯酮的合成不受猪CYP17基因编码区中任何多态性的直接影响。

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