Gomez-Santos Laura, Vazquez-Chantada Mercedes, Mato Jose Maria, Martinez-Chantar Maria Luz
Metabolomics Unit, CIC bioGUNE, Technology Park of Bizkaia, Bizkaia, Basque Country, Spain.
Methods Mol Biol. 2012;826:133-49. doi: 10.1007/978-1-61779-468-1_12.
S-Adenosylmethionine, abbreviated as SAM, SAMe or AdoMet, is the principal methyl group donor in the mammalian cell and the first step metabolite of the methionine cycle, being synthesized by MAT (methionine adenosyltransferase) from methionine and ATP. About 60 years after its identification, SAMe is admitted as a key hepatic regulator whose level needs to be maintained within a specific range in order to avoid liver damage. Recently, in vitro and in vivo studies have demonstrated the regulatory role of SAMe in HGF (hepatocyte growth factor)-mediated hepatocyte proliferation through a mechanism that implicates the activation of the non-canonical LKB1/AMPK/eNOS cascade and HuR function. Regarding hepatic differentiation, cellular SAMe content varies depending on the status of the cell, being lower in immature than in adult hepatocytes. This finding suggests a SAMe regulatory effect also in this cellular process, which very recently was reported and related to HuR activity. Although in the last years this and other discoveries contributed to throw light into the tangle of regulatory mechanisms that govern this complex process, an overall understanding is still a challenge. For this purpose, the in vitro hepatic differentiation culture systems by using stem cells or fetal hepatoblasts are considered as valuable tools which, in combination with the methods used in current days to elucidate cell signaling pathways, surely will help to clear up this question.
S-腺苷甲硫氨酸，简称为SAM、SAMe或AdoMet，是哺乳动物细胞中的主要甲基供体，也是甲硫氨酸循环的第一步代谢产物，由甲硫氨酸腺苷转移酶（MAT）从甲硫氨酸和ATP合成。在其被鉴定约60年后，SAMe被认为是一种关键的肝脏调节因子，其水平需要维持在特定范围内以避免肝脏损伤。最近，体外和体内研究表明，SAMe通过涉及非经典LKB1/AMPK/eNOS级联激活和HuR功能的机制，在肝细胞生长因子（HGF）介导的肝细胞增殖中发挥调节作用。关于肝脏分化，细胞内SAMe含量因细胞状态而异，未成熟肝细胞中的含量低于成熟肝细胞。这一发现表明SAMe在这一细胞过程中也具有调节作用，最近有报道称这与HuR活性有关。尽管在过去几年中，这一发现和其他发现有助于揭示控制这一复杂过程的调节机制，但全面理解仍然是一项挑战。为此，利用干细胞或胎儿肝母细胞的体外肝脏分化培养系统被认为是有价值的工具，结合当前用于阐明细胞信号通路的方法，肯定有助于解决这个问题。
