Boersma M G, Primus J L, Koerts J, Veeger C, Rietjens I M
Laboratory of Biochemistry and Division of Toxicology,Wageningen University, The Netherlands.
Eur J Biochem. 2000 Nov;267(22):6673-8. doi: 10.1046/j.1432-1327.2000.01764.x.
The mechanism of microperoxidase-8 (MP-8) mediated O- and N-dealkylation was investigated. In the absence of ascorbate (peroxidase mode), many unidentified polymeric products are formed and the extent of substrate degradation correlates (r = 0.94) with the calculated substrate ionization potential, reflecting the formation of radical intermediates. In the presence of ascorbate (P450 mode) formation of polymeric products is largely prevented but, surprisingly, dealkylation is not affected. In addition, aromatic hydroxylation and oxidative dehalogenation is observed. The results exclude a radical mechanism and indicate the involvement of a (hydro)peroxo-iron heme intermediate in P450-type of heteroatom dealkylation.
研究了微过氧化物酶-8（MP-8）介导的O-和N-脱烷基化机制。在没有抗坏血酸的情况下（过氧化物酶模式），会形成许多未鉴定的聚合产物，底物降解程度与计算出的底物电离势相关（r = 0.94），这反映了自由基中间体的形成。在有抗坏血酸的情况下（P450模式），聚合产物的形成在很大程度上得到了抑制，但令人惊讶的是，脱烷基化并未受到影响。此外，还观察到了芳香族羟基化和氧化脱卤反应。结果排除了自由基机制，并表明在P450型杂原子脱烷基化中涉及（氢）过氧铁血红素中间体。
