Suicidal inactivation of cytochrome P-450. Formation of a heme-substrate covalent adduct.

Suicidal inactivation of cytochrome P-450. Formation of a heme-substrate covalent adduct.
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细胞色素 P-450 的自杀性失活。

DOI:
10.1016/0006-291x(78)90407-2
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发表时间:
1978
影响因子:
3.1
通讯作者:
Garold S. Yost
Garold S. Yost
中科院分区:
生物学4区
文献类型:
--
作者:
P. O. D. de Montellano;B. Mico;Garold S. Yost

文献摘要

被引文献

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对2-(14 C)-2-异丙基-4-戊烯酰胺(烯丙基异丙基乙酰胺,AIA)给药后苯巴比妥预处理大鼠肝脏中蓄积的绿色色素进行放射性标记。通过HPLC(λmax(CHCl 3)417、512、545、594、652 nm)分离的单一主要绿色藜芦醇组分干净地转化为锌络合物(λmax(CHCl 3)431、547、591、634、669 nm)。在锌络合物形成后,TLC和HPLC上的放射性标记随发色团发生定量位移。发色团吸光度与放射性标记含量的相关性表明形成了1:1的卟啉-AIA加合物。因此,细胞色素P-450被自身催化的AIA加成到其血红素辅基上而被破坏。
The green pigment accumulated in the livers of phenobarbital pretreated rats after administration of 2-(14C)-2-isopropyl-4-pentenamide (allylisopropylacetamide, AIA) is radiolabeled. The single primary green prophyrin component isolated by HPLC (λmax(CHCl3) 417, 512, 545, 594, 652 nm) is cleanly converted to a zinc complex (λmax(CHCl3) 431, 547, 591, 634, 669 nm). The radiolabel quantitatively shifts with the chromophore on TLC and HPLC upon formation of the zinc complex. Correlation of chromophore absorbance with radiolabel content suggests the formation of a 1:1 porphyrin-AIA adduct. Cytochrome P-450 is therefore destroyed by self-catalyzed addition of AIA to its heme prosthetic group.