Chiang P K, Gordon R K, Tal J, Zeng G C, Doctor B P, Pardhasaradhi K, McCann P P
Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
FASEB J. 1996 Mar;10(4):471-80.
S-Adenosylmethionine (AdoMet or SAM) plays a pivotal role as a methyl donor in a myriad of biological and biochemical events. Although it has been claimed that AdoMet itself has therapeutic benefits, it remains to be established whether it can be taken up intact by cells. S-Adenosylhomocysteine (AdoHcy), formed after donation of the methyl group of AdoMet to a methyl acceptor, is then hydrolyzed to adenosine and homocysteine by AdoHcy hydrolase. This enzyme has long been a target for inhibition as its blockade can affect methylation of phospholipids, proteins, DNA, RNA, and other small molecules. Protein carboxymethylation may be involved in repair functions of aging proteins, and heat shock proteins are methylated in response to stress. Bacterial chemotaxis involves carboxymethylation and demethylation in receptor-transducer proteins, although a similar role in mammalian cells is unclear. The precise role of phospholipid methylation remains open. DNA methylation is related to mammalian gene activities, somatic inheritance, and cellular differentiation. Activation of some genes has been ascribed to the demethylation of critical mCpG loci, and silencing of some genes may be related to the methylation of specific CpG loci. Viral DNA genomes exist in cells as extrachromosomal units and are generally not methylated, although once integrated into host chromosomes, different patterns of methylation are correlated with altered paradigms of transcriptional activity. Some viral latency may be related to DNA methylation. Cellular factors have been found to interact with methylated DNA sequences. Methylation of mammalian ribosomal RNAs occurs soon after the synthesis of its 47S precursor RNA in the nucleolus before cleavage to smaller fragments. Inhibition of the methylation of rRNA affects its processing to mature 18S and 28S rRNAs. The methylation of 5'-terminal cap plays an important role in mRNA export from the nucleus, efficient translation, and protection of the integrity of mRNAs. Another important function of AdoMet is that it serves as the sole donor of an aminopropyl group that is conjugated with putrescine to form, first, the polyamine spermidine, and then spermine.
S-腺苷甲硫氨酸（AdoMet或SAM）作为甲基供体，在众多生物和生化过程中发挥着关键作用。尽管有人声称AdoMet本身具有治疗益处，但它是否能被细胞完整摄取仍有待确定。S-腺苷同型半胱氨酸（AdoHcy）是AdoMet的甲基基团捐赠给甲基受体后形成的，随后被AdoHcy水解酶水解为腺苷和同型半胱氨酸。长期以来，这种酶一直是抑制的靶点，因为其阻断会影响磷脂、蛋白质、DNA、RNA和其他小分子的甲基化。蛋白质羧甲基化可能参与衰老蛋白质的修复功能，热休克蛋白在应激反应中会发生甲基化。细菌趋化作用涉及受体-转导蛋白中的羧甲基化和去甲基化，尽管其在哺乳动物细胞中的类似作用尚不清楚。磷脂甲基化的确切作用仍不明确。DNA甲基化与哺乳动物基因活性、体细胞遗传和细胞分化有关。一些基因的激活归因于关键mCpG位点的去甲基化，一些基因的沉默可能与特定CpG位点的甲基化有关。病毒DNA基因组作为染色体外单位存在于细胞中，通常不被甲基化，尽管一旦整合到宿主染色体中，不同的甲基化模式与转录活性的改变模式相关。一些病毒潜伏期可能与DNA甲基化有关。已发现细胞因子与甲基化DNA序列相互作用。哺乳动物核糖体RNA在核仁中合成其47S前体RNA后不久，在切割成较小片段之前就会发生甲基化。抑制rRNA的甲基化会影响其加工成成熟的18S和28S rRNA。5'-末端帽的甲基化在mRNA从细胞核输出、有效翻译以及保护mRNA完整性方面起着重要作用。AdoMet的另一个重要功能是它作为氨基丙基的唯一供体，氨基丙基与腐胺结合，首先形成多胺亚精胺，然后形成精胺。
