Dalet C, Andersson K K, Dalet-Beluche I, Bonfils C, Maurel P
Biochem Pharmacol. 1983 Feb 15;32(4):593-601. doi: 10.1016/0006-2952(83)90481-1.
The effect of polyamines on the activity of the mixed-function oxidase (MFO) system from human, rat and rabbit liver microsomes was investigated in detail. It was shown that polyamine (spermine) stimulates NADPH-dependent activity of the MFO system several-fold whatever the substrate (foreign drug or natural), not only with microsomes but also with the reconstituted system consisting of highly purified cytochrome P-450 (LM2 isozyme), cytochrome P-450 NADPH reductase and dilauroylphosphorylcholine. Stimulation (extent and concentration dependence) appeared to be dependent on a number of parameters such as ionic strength, pH, animal species and treatment, nature of the substrate, and was stereospecific (different effect on 6 beta-and 16 alpha-testosterone hydroxylation). Further, the spermine effect was evaluated on some elementary steps of the cytochrome P-450 reaction cycle, like substrate binding, P-450 reduction and second electron transfer. Finally, it was shown that the organic peroxide dependent activity was not stimulated by spermine with microsomes nor with the purified P-450 LM2 isozyme. On the basis of this study, it was concluded that the locus of polyamine action is cytochrome P-450 and that stimulation could result either from increased stability of the oxyferrous intermediate of P-450 or from an increased rate of second electron transfer from reductase to P-450.
详细研究了多胺对人、大鼠和兔肝微粒体混合功能氧化酶（MFO）系统活性的影响。结果表明，无论底物是外来药物还是天然物质，多胺（精胺）均可使MFO系统依赖NADPH的活性提高数倍，不仅对微粒体如此，对由高度纯化的细胞色素P - 450（LM2同工酶）、细胞色素P - 450 NADPH还原酶和二月桂酰磷脂酰胆碱组成的重组系统也是如此。刺激作用（程度和浓度依赖性）似乎取决于许多参数，如离子强度、pH值、动物种类和处理方式、底物性质，并且具有立体特异性（对6β-和16α-睾酮羟化有不同影响）。此外，还评估了精胺对细胞色素P - 450反应循环的一些基本步骤的影响，如底物结合、P - 450还原和第二次电子转移。最后，结果表明，无论是微粒体还是纯化的P - 450 LM2同工酶，精胺都不会刺激有机过氧化物依赖性活性。基于这项研究，得出结论：多胺作用的位点是细胞色素P - 450，刺激可能是由于P - 450的氧亚铁中间体稳定性增加，或者是由于从还原酶到P - 450的第二次电子转移速率增加所致。
