Mato J M, Alvarez L, Ortiz P, Mingorance J, Durán C, Pajares M A
Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.
Adv Exp Med Biol. 1994;368:113-7. doi: 10.1007/978-1-4615-1989-8_11.
Methionine metabolism impairment in human liver disease has been related with an alteration in SAM-synthetase. This deficiency is produced by a post-translational event since human liver cirrhosis presents normal levels of SAM-synthetase mRNA in spite of a more than 50% diminution in its activity. A series of different experiments on the structure and activity of this enzyme have provided strong evidence that SAM-synthetase is regulated by reduced/oxidized glutathione ratio. Restoration of glutathione levels by the addition of S-adenosyl-methionine or glutathione esters in various experimental conditions (buthionine sulfoximine and carbon tetrachloride intoxication) resulted in a normalization of the SAM-synthetase diminution caused by the toxics and an attenuation of the morfological alteration produced in the liver, including fiber production. This findings might have pharmacological implications in the treatment of liver diseases, since the possible beneficial effect of long term administration of SAM could include a reduction of fiber production.
人类肝脏疾病中的甲硫氨酸代谢受损与S-腺苷甲硫氨酸合成酶的改变有关。这种缺陷是由翻译后事件引起的，因为尽管人类肝硬化患者的S-腺苷甲硫氨酸合成酶活性降低了50%以上，但其mRNA水平正常。一系列关于该酶结构和活性的不同实验提供了强有力的证据，表明S-腺苷甲硫氨酸合成酶受还原型/氧化型谷胱甘肽比值的调节。在各种实验条件下（丁硫氨酸亚砜胺和四氯化碳中毒）通过添加S-腺苷甲硫氨酸或谷胱甘肽酯来恢复谷胱甘肽水平，导致由毒物引起的S-腺苷甲硫氨酸合成酶减少正常化，并减轻肝脏中产生的形态学改变，包括纤维生成。这些发现可能对肝脏疾病的治疗具有药理学意义，因为长期施用S-腺苷甲硫氨酸的可能有益作用可能包括减少纤维生成。
