Sawahata T, Neal R A
Mol Pharmacol. 1982 Mar;21(2):464-7.
The inhibition of rat liver microsomal cytochrome P-450 by benzyl hydrodisulfide has been examined as a model system for the inactivation of cytochrome P-450 seen during the microsomal metabolism of thiono-sulfur-containing compounds. Benzyl hydrodisulfide decreased enzymatic activity toward benzphetamine when incubated with hepatic microsomes prior to the assay for monooxygenase activity. In addition, incubation of microsomes with the hydrodisulfide caused a decrease in the level of cytochrome P-450 detectable as its carbon monoxide complex as well as a decrease in heme detectable as its pyridine-hemochromogen. In a typical experiment, the loss of enzymatic activity, cytochrome P-450, and heme were 65, 56, and 51%, respectively. These data suggest that the major loss of monooxygenase activity and of cytochrome P-450 which was seen on incubation of microsomes with benzyl hydrodisulfide results from an alteration in the structure of the heme moiety of cytochrome P-450. A similar alteration in the heme moiety of cytochrome P-450 is believed to be responsible, in part, for the loss of monooxygenase activity and cytochrome P-450 seen on incubation of parathion and other thiono-sulfur-containing compounds with hepatic microsomes or a reconstituted cytochrome P-450-containing monooxygenase system.
作为硫代含硫化合物微粒体代谢过程中细胞色素P - 450失活的模型系统，已对苄基二硫化物对大鼠肝脏微粒体细胞色素P - 450的抑制作用进行了研究。在测定单加氧酶活性之前，将苄基二硫化物与肝微粒体一起孵育时，其对苄非他明的酶活性降低。此外，微粒体与二硫化物孵育导致作为一氧化碳复合物可检测到的细胞色素P - 450水平降低，以及作为吡啶-血色原可检测到的血红素水平降低。在一个典型实验中，酶活性、细胞色素P - 450和血红素的损失分别为65%、56%和51%。这些数据表明，微粒体与苄基二硫化物孵育时观察到的单加氧酶活性和细胞色素P - 450的主要损失是由于细胞色素P - 450血红素部分结构的改变所致。细胞色素P - 450血红素部分的类似改变被认为部分是导致对硫磷和其他硫代含硫化合物与肝微粒体或重组的含细胞色素P - 450单加氧酶系统孵育时观察到的单加氧酶活性和细胞色素P - 450损失的原因。
