Insight into the polar reactivity of the onium chalcogen analogues of S-adenosyl-L-methionine
Insight into the polar reactivity of the onium chalcogen analogues of S-adenosyl-L-methionine
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DOI：
10.1021/bi048693
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发表时间：
2004-10-26
期刊：
影响因子：
2.9
通讯作者：
Booker, SJ
中科院分区：
文献类型：
--
作者：
Iwig, DF;Booker, SJ
S-腺苷-L-甲硫氨酸（S-Adenosyl-L-methionine，简称S-Met）是自然界中最具多样性的代谢产物之一，不仅用于大量的生物反应，而且适用于几种不同的反应模式。它所涉及的转化类型包括脱羧、与中心硫原子键合的三个碳原子中的任何一个亲电加成、在与锍相邻的碳原子处去除质子以及还原裂解以产生5 '-脱氧腺苷5'-自由基中间体。在生理pH值和温度下，蛋氨酸会经历三种自发降解途径，其中第一种是手性锍基团的外消旋化，其以不依赖于pH值的方式发生。其余两种途径是pH依赖性的，包括（1）α-羧酸基团分子内攻击γ-碳，提供L-高丝氨酸内酯（HSL）和5 '-甲硫基腺苷（NITA），以及（2）C-5'去质子化，引发级联反应，导致腺嘌呤和S-核糖基甲硫氨酸的形成。在此，我们描述了pH值依赖性的稳定性研究，在37 degreesC和恒定的离子强度，我们使用作为探针的相对固有的反应性，硒-腺苷-L-硒代蛋氨酸和碲-腺苷-L-碲甲硫氨酸（硒蛋氨酸和碲蛋氨酸，分别），硒蛋氨酸及其硒和碲类似物。我们发现，用Na 2 Met分子内亲核攻击得到HSL和MTA，其pH-速率曲线具有两个可滴定基团，表观pK（a）值为1.2 +/- 0.4和8.2 +/- 0.05，并显示一级速率常数为
S-Adenosyl-L-methionine (AdoMet) is one of Nature's most diverse metabolites, used not only in a large number of biological reactions but amenable to several different modes of reactivity. The types of transformations in which it is involved include decarboxylation, electrophilic addition to any of the three carbons bonded to the central sulfur atom, proton removal at carbons adjacent to the sulfonium, and reductive cleavage to generate 5'-deoxyadenosyl 5'-radical intermediates. At physiological pH and temperature, AdoMet is subject to three spontaneous degradation pathways, the first of which is racemization of the chiral sulfonium group, which takes place in a pH-independent manner. The two remaining pathways are pH-dependent and include (1) intramolecular attack of the alpha-carboxylate group onto the gamma-carbon, affording L-homoserine lactone (HSL) and 5'-methylthioadenosine (NITA), and (2) deprotonation at C-5', initiating a cascade that results in formation of adenine and S-ribosylmethionine. Herein, we describe pH-dependent stability studies of AdoMet and its selenium and tellurium analogues, Se-adenosyl-L-selenomethionine and Te-adenosyl-L-telluromethionine (SeAdoMet and TeAdoMet, respectively), at 37 degreesC and constant ionic strength, which we use as a probe of their relative intrinsic reactivities. We find that with AdoMet intramolecular nucleophilic attack to afford HSL and MTA exhibits a pH-rate profile having two titratable groups with apparent pK(a) values of 1.2 +/- 0.4 and 8.2 +/- 0.05 and displaying firstorder rate constants of