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苯巴比妥及其类似物对可溶性细菌细胞色素P-450单加氧酶的非底物诱导作用。

Nonsubstrate induction of a soluble bacterial cytochrome P-450 monooxygenase by phenobarbital and its analogs.

作者信息

Fulco A J, Kim B H, Matson R S, Narhi L O, Ruettinger R T

出版信息

Mol Cell Biochem. 1983;53-54(1-2):155-61. doi: 10.1007/BF00225251.

DOI:10.1007/BF00225251
PMID:6413835
Abstract

A soluble, cytochrome P-450-dependent fatty acid hydroxylase--epoxidase complex from Bacillus megaterium ATCC 14581 can be induced more than 100-fold by the addition of phenobarbital or one of its analogs (hexobarbital) to the growth medium. These barbiturate inducers are apparently not substrates for the enzyme nor do they activate the monooxygenase in the cell-free system. The induction efficiency of both phenobarbital and hexobarbital can be significantly increased with respect to monooxygenase activity by autoclaving the inducer in the growth medium rather than by adding it to the medium after autoclaving. Turnover numbers of about 3 000 nmoles of substrate oxygenated per min per nmole of P-450 were obtained in crude cell-free preparations obtained from maximally induced cultures. Our data indicate that products formed by heating phenobarbital or hexobarbital in the growth medium are significantly better inducers of monooxygenase activity than are the unaltered drugs.

摘要

通过在巨大芽孢杆菌ATCC 14581的生长培养基中添加苯巴比妥或其类似物之一(己巴比妥),可诱导出一种可溶性的、细胞色素P - 450依赖性脂肪酸羟化酶 - 环氧化酶复合物,其诱导倍数超过100倍。这些巴比妥类诱导剂显然不是该酶的底物,在无细胞体系中也不会激活单加氧酶。相对于单加氧酶活性,通过在生长培养基中对诱导剂进行高压灭菌,而非在高压灭菌后添加到培养基中,可显著提高苯巴比妥和己巴比妥的诱导效率。从最大诱导培养物中获得的粗无细胞制剂中,每纳米摩尔P - 450每分钟可氧化约3000纳米摩尔底物,周转数达到此值。我们的数据表明,在生长培养基中加热苯巴比妥或己巴比妥形成的产物作为单加氧酶活性的诱导剂,比未改变的药物效果要好得多。

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本文引用的文献

1
Induction and specificity of a (cytochrome P-450)-dependent laurate in-chain-hydroxylase from higher plant microsomes.高等植物微粒体中一种(细胞色素P-450)依赖性月桂酸链中羟化酶的诱导与特异性
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Species differences in responsiveness to 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene, a potent phenobarbital-like inducer of microsomal monooxygenase activity.对1,4-双[2-(3,5-二氯吡啶氧基)]苯(一种强力的类似苯巴比妥的微粒体单加氧酶活性诱导剂)反应性的种属差异。
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Genetic mechanisms controlling the induction of polysubstrate monooxygenase (P-450) activities.
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camR, a negative regulator locus of the cytochrome P-450cam hydroxylase operon.camR,细胞色素P-450cam羟化酶操纵子的一个负调控基因座。
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Phenobarbital induction of a soluble cytochrome P-450-dependent fatty acid monooxygenase in Bacillus megaterium.苯巴比妥对巨大芽孢杆菌中一种可溶性细胞色素P-450依赖性脂肪酸单加氧酶的诱导作用。
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