Hydrolysis of benzo[a]pyrene diol epoxide and its covalent binding to DNA proceed through similar rate-determining steps.
Hydrolysis of benzo[a]pyrene diol epoxide and its covalent binding to DNA proceed through similar rate-determining steps.
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苯并[a]芘二醇环氧化物的水解及其与DNA的共价结合通过类似的速率决定步骤进行。
DOI：
10.1073/pnas.81.9.2635
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发表时间：
1984
影响因子：
11.1
通讯作者：
Bond,DM
中科院分区：
文献类型：
--
作者：
Meehan,T;Bond,DM
苯并[a]芘的致突变和致癌代谢物(7R,8S)-二羟基-(9R,10R)-环氧- 7,8,9,10 -四氢苯并[a]芘在DNA存在下发生两个主要反应：(i)水解和（ii）共价结合。我们报道水解和共价结合是特定的和一般的酸催化反应，具有相同或类似的速率决定步骤。为了解释共价结合和水解中速率决定步骤的相似性，我们提出并测试了两个模型。在每个模型中，速率决定步骤导致形成一个碳离子，它作为四醇和加合物的前体。在模型A中，碳离子被划分为两个结构域（1和2），而在模型B中只有一个结构域。伪一阶速率常数、生成物比和速率比的测量结果支持模型A，而动力学结果与模型b不一致。结构域1很可能代表嵌入DNA中的活化苯并[A]芘，而结构域2碳氢化合物则物理地结合在DNA螺旋的外部。
The mutagenic and carcinogenic metabolite of benzo[a]pyrene, (7R,8S)-dihydroxy-(9R,10R)-epoxy-7,8, 9,10-tetrahydrobenzo[a]pyrene, undergoes two major reactions in the presence of DNA: (i) hydrolysis and (ii) covalent binding. We report that hydrolysis and covalent binding are specific and general acid-catalyzed reactions with the same or similar rate-determining steps. To account for the similarity of rate-determining steps in covalent binding and hydrolysis we propose and test two models. In each model, the rate-determining step results in formation of a carbonium ion, which serves as a precursor for both tetrol and adduct. In model A the carbonium ion is partitioned between two domains (1 and 2), while in model B there is only one domain. Measurements of pseudo-first-order rate constants, product ratios, and rate ratios support model A, while kinetic results are inconsistent with model B. Domain 1 most likely represents activated benzo[a]pyrenes that are intercalated into DNA, while domain 2 hydrocarbons are physically bound to the outside of the DNA helix.