Rajamanickam C, Amrutavalli J, Rao M R, Padmanaban G
Biochem J. 1972 Sep;129(2):381-7. doi: 10.1042/bj1290381.
Several drugs are known to induce the liver microsomal mixed-function oxidase system when administered in vivo or even in vitro in cell culture. A sequence of events has been suggested in which the drug is visualized to induce delta-aminolaevulinate synthetase, the first and rate-limiting enzyme of the haem-biosynthetic pathway, which is followed by enhanced haem synthesis and cytochrome P-450 content, facilitating the increase in the drug-metabolizing activity of the liver microsomal fraction. The present studies show that the fungicide hexachlorobenzene, when administered to female rats, can lead to enhanced amounts and rate of synthesis of cytochrome P-450 under conditions when the rate of total haem synthesis has not appreciably altered. The subsequent increase in the rate of total haem synthesis as well as the initial increase in amounts of cytochrome P-450 are brought about under conditions when delta-aminolaevulinate synthetase activity remains constant. However, manifestation of porphyria due to prolonged drug administration is accompanied by a twofold increase in delta-aminolaevulinate synthetase activity. The increase in enzyme activity appears to be due to a decreased degradation rate of the enzyme.
已知有几种药物在体内给药甚至在细胞培养的体外环境中时，会诱导肝微粒体混合功能氧化酶系统。有人提出了一系列事件，其中药物被认为可诱导δ-氨基乙酰丙酸合成酶，这是血红素生物合成途径中的第一个且限速的酶，随后血红素合成和细胞色素P-450含量增加，促进了肝微粒体部分药物代谢活性的提高。目前的研究表明，给雌性大鼠施用杀真菌剂六氯苯时，在总血红素合成速率没有明显改变的情况下，可导致细胞色素P-450的合成量和合成速率增加。在δ-氨基乙酰丙酸合成酶活性保持恒定的情况下，随后总血红素合成速率的增加以及细胞色素P-450量的最初增加得以实现。然而，由于长期给药导致的卟啉症表现伴随着δ-氨基乙酰丙酸合成酶活性增加两倍。酶活性的增加似乎是由于酶的降解速率降低所致。
