rat liver microsomal cytochrome P₄₅₀

• 英文名称: rat liver microsomal cytochrome P₄₅₀

反应信息

• 作为试剂：
  描述：

  对乙酰氨基酚 在 rat liver microsomal cytochrome P₄₅₀ dipotassium hydrogenphosphate 、 potassium dihydrogenphosphate 、 还原型辅酶II(NADPH)四钠盐 、 catalase 作用下， 反应 0.17h， 生成 N-乙酰苯醌亚胺
  参考文献：
  名称：

  Rat liver microsomal cytochrome P450-dependent oxidation of 3,5-disubstituted analogues of paracetamol

  摘要：

  1. The cytochrome P450-dependent binding of paracetamol and a series of 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -CH3, -C2H5, -iC(3)H(7)) have been determined with beta-naphthoflavone (beta NF)-induced rat liver microsomes and produced reverse type I spectral changes. K-s,K-app varied from 0.14 mM for 3,5-diiC(3)H(7)-paracetamol to 2.8 mM for paracetamol.2. All seven analogues underwent rat liver microsomal cytochrome P450-dependent oxidation, as reflected by the formation of GSSG in the presence of GSH. The GSSG-formation was increased in all cases upon pretreatment of rats by beta-naphthoflavone (beta NF) and was generally decreased upon pretreatment by phenobarbital (PB).3. Rat liver microsomal cytochrome P450 as well as horseradish peroxidase catalysed the formation of 3,5-disubstituted NAPQI analogues from the corresponding parent compounds, as identified by UV-spectrophotometry of the NAPQI analogues and by GC/MS detection of the following GSH-conjugates: 2-glutathione-S-yl-3,5-dimethyl-1,4-dihydroxybenzene, 2-glutathione-S-yl-3,5-dichloro-paracetamol, and 2-glutathione-S-yl-3,5-dibromo-paracetamol.4. In liver microsomal (beta NF-induced) incubations, apparent K,values, as determined for the cytochrome P450 catalysis-dependent oxidation of GSH, for seven 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -CH3, -C2H5, iC(3)H(7)) varied from 0.07 to 0.64 mM. Paracetamol exhibited an apparent K-m of 0.73 mM. Apparent V-max values for the cytochrome P450 catalysis dependent oxidation of GSH varied from 0.66 nmol min(-1) mg(-1)protein for paracetamol to 3.0 nmol min(-1) mg(-1) protein for 3,5-dimethyl-paracetamol.

  DOI：

  10.3109/00498259609046740