Denaturation of cytochrome P-450 by cyclophosphamide metabolites.
Denaturation of cytochrome P-450 by cyclophosphamide metabolites.
复制标题
环磷酰胺代谢物使细胞色素 P-450 变性。
DOI：
10.1016/0006-291x(78)91369-4
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发表时间：
1978
影响因子：
3.1
通讯作者：
B. Paul
中科院分区：
文献类型：
--
作者：
A. Marinello;H. Gurtoo;R. Struck;B. Paul
环磷酰胺(CP)的代谢产物丙烯醛和4-羟基-CP对大鼠肝微粒体细胞色素P-450有变性作用，而另一种代谢物磷酰胺芥末本身或其类似物异环磷酰胺无此作用。CP代谢产物产生的变性可被半胱氨酸阻断，提示CP代谢产物S与半胱氨酸中的巯基以及细胞色素P-450中可能存在相互作用。这些研究可能解释了高剂量CP对各种微粒体混合功能加氧酶活性的特异性抑制的生化基础。
Cyclophosphamide (CP) metabolites, acrolein and 4-hydroxy-CP, were found to denature rat liver microsomal cytochrome P-450, whereas another metabolite, phosphoramide mustard, CP per se or its analog Ifosfamide had no effect. The denaturation produced by CP metabolites could be blocked by cysteine, suggesting an interaction between CP metabolite (s) and sulfhydryl groups in cysteine and probably in cytochrome P-450. These studies might explain the biochemical basis of the specific depression of various microsomal mixed function oxygenase activities produced by high doses of CP.