Lovisetto P, Giorcelli W, Actis G C, Biarese V
Minerva Med. 1976 Sep 29;67(45):2903-8.
After a brief survey of the various modifications that may be encountered by drugs through the work of systems that detoxify the liver cell, attention is given to the problem of enzymic induction. The latter is the result of derepression of a gene that codes for a given enzyme; at the molecular level, derepression takes place when the substrate, by changing the tertiary structure of the repressor, brings about its detachment from DNA: in this way, RNA-polymerase is made capable of synthesising the corresponding mRNA. The inducing activity of phenobarbitone, a drug employed classically in the management of Gilbertian forms, must be substantially attributed to an increase in the synthesis of microsomial proteins, as shown by studies with labelled amino acids.
在简要考察了药物在肝细胞解毒系统作用下可能发生的各种修饰之后,接下来关注酶诱导问题。酶诱导是编码特定酶的基因去阻遏的结果;在分子水平上,当底物通过改变阻遏物的三级结构使其从DNA上脱离时,就会发生去阻遏:这样,RNA聚合酶就能够合成相应的mRNA。苯巴比妥是经典用于治疗吉尔伯特型的药物,其诱导活性必须主要归因于微粒体蛋白合成的增加,这已通过用标记氨基酸进行的研究得到证实。