Lieber Charles S
Mount Sinai School of Medicine, Alcohol Research Center, Section of Liver Disease and Nutrition, Bronx Veterans Affairs Medical Center, NY 10468, USA.
Am J Clin Nutr. 2002 Nov;76(5):1183S-7S. doi: 10.1093/ajcn/76/5.1183S.
S-Adenosyl-L-methionine (SAMe) exerts many key functions in the liver, including serving as a precursor for cysteine, 1 of 3 amino acids of glutathione--the major physiologic defense mechanism against oxidative stress. SAMe is particularly important in opposing the toxicity of free oxygen radicals generated by various pathogens, including alcohol, which cause oxidative stress largely by the induction of cytochrome P4502E1 (CYP2E1) and by its metabolite acetaldehyde. SAMe also acts as the main methylating agent in the liver. The precursor of SAMe is methionine, one of the essential amino acids, which is activated by SAMe-synthetase (EC 2.5.1.6). Unfortunately, the activity of this enzyme is significantly decreased as a consequence of liver disease. Because of decreased utilization, methionine accumulates and, simultaneously, there is a decrease in SAMe that acquires the status of an essential nutrient and therefore must be provided exogenously as a supernutrient to compensate for its deficiency. Administration of this innocuous supernutrient results in many beneficial effects in various tissues, mainly in the liver, and especially in the mitochondria. This was shown in alcohol-fed baboons and in other experimental models of liver injury and in clinical trials, some of which are reviewed in other articles in this issue.
S-腺苷-L-蛋氨酸（SAMe）在肝脏中发挥多种关键功能，包括作为半胱氨酸的前体，半胱氨酸是谷胱甘肽三种氨基酸之一，谷胱甘肽是对抗氧化应激的主要生理防御机制。SAMe在对抗各种病原体产生的游离氧自由基毒性方面尤为重要，这些病原体包括酒精，酒精主要通过诱导细胞色素P4502E1（CYP2E1）及其代谢产物乙醛来引起氧化应激。SAMe在肝脏中还充当主要的甲基化剂。SAMe的前体是蛋氨酸，它是必需氨基酸之一，由SAMe合成酶（EC 2.5.1.6）激活。不幸的是，由于肝脏疾病，这种酶的活性显著降低。由于利用率降低，蛋氨酸积累，同时，SAMe减少，SAMe成为一种必需营养素，因此必须作为超级营养素外源提供以弥补其缺乏。给予这种无害的超级营养素会在各种组织中产生许多有益作用，主要是在肝脏中，尤其是在肝脏线粒体中。这在喂食酒精的狒狒以及其他肝损伤实验模型和临床试验中得到了证实，本期其他文章对其中一些试验进行了综述。
