S-adenosylmethionine:: jack of all trades and master of everything?
S-adenosylmethionine:: jack of all trades and master of everything?
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DOI：
10.1042/bst0340330
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发表时间：
2006-04-01
影响因子：
3.9
通讯作者：
Loenen, WAM
中科院分区：
文献类型：
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作者：
Loenen, WAM
SAM（S-腺苷甲硫氨酸，也称为腺苷蛋氨酸）是众所周知的大多数甲基转移酶的甲基供体，所述甲基转移酶修饰DNA、RNA、组蛋白和其他蛋白质，决定复制、转录和翻译保真度、错配修复、染色质建模、表观遗传修饰和印迹，这些都是癌症研究和衰老中非常感兴趣和重要的主题。总共有15个SAM结合蛋白超家族被鉴定，具有许多额外的功能，从磷脂和小分子（如砷）的甲基化到多胺的合成或自由基的形成。SAM是从脱甲基SAM通过甲硫氨酸循环再生，其中涉及叶酸。人类中这种循环的不平衡，例如通过膳食不足引起的叶酸缺乏、酒精滥用、砷中毒或遗传因素，导致SAM的消耗和人类疾病。除了作为修饰酶的甲基供体保护细菌DNA不受同源限制外，SAM还作为核酸酶如I型限制酶EcoKI的辅因子，其在没有SAM的情况下不能限制DNA。最后，在一个完全不同的策略，SAM可以结合到某些RNA结构称为核糖开关，控制转录或翻译。这样，多个基因的表达可以以SAM依赖的方式调节，这是一个意外的发现，为基因控制开辟了新的途径。这篇小综述讨论了这种小代谢物的一些不同和惊人的作用。
SAM (S-adenosyl methionine, also known as AdoMet) is well known as the methyl donor for the majority of methyltransferases that modify DNA, RNA, histones and other proteins, dictating replicational, transcriptional and translational fidelity, mismatch repair, chromatin modelling, epigenetic modifications and imprinting, which are all topics of great interest and importance in cancer research and aging. In total, 15 superfamilies of SAM-binding proteins have been identified, with many additional functions varying from methylation of phospholipids and small molecules such as arsenic to synthesis of polyamines or radical formation. SAM is regenerated from demethylated SAM via the methionine cycle, which involves folate. imbalance of this cycle in humans, e.g. through folate shortage via dietary insufficiency, alcohol abuse, arsenic poisoning or hereditary factors, leads to depletion of SAM and human disease. in addition to its role as a methyl donor to modification enzymes that protect bacterial DNA against cognate restriction, SAM also serves as a co-factor for nucleases such as the type I restriction enzyme EcoKI, which is unable to restrict DNA in the absence of SAM. Finally, on a completely different tack, SAM can bind to certain RNA structures called riboswitches that control transcription or translation. in this way, expression of multiple genes can be regulated in a SAM-dependent manner, an unexpected finding that opens up new avenues into gene control. This minireview discusses some of these diverse and amazing roles of this small metabolite.