Lee Taunia D, Sadda Mamatha R, Mendler Michel H, Bottiglieri Teodoro, Kanel Gary, Mato José M, Lu Shelly C
Division of Gastroenterology and Liver Diseases, University of Southern California Liver Disease Research Center, University of Southern California/University of California, USA.
Alcohol Clin Exp Res. 2004 Jan;28(1):173-81. doi: 10.1097/01.ALC.0000108654.77178.03.
Abnormal methionine metabolism occurs in animals fed ethanol and in end-stage cirrhotic patients. Expected consequences of these abnormalities include reduced hepatic S-adenosylmethionine and glutathione (GSH) levels, impaired transmethylation, and reduced homocysteine catabolism, resulting in the often-observed hyperhomocystinemia in cirrhotic patients. These parameters have not been examined simultaneously in patients with less advanced alcoholic liver disease.
Six patients hospitalized for alcoholic hepatitis were studied. Plasma was analyzed for homocysteine, methionine, and GSH levels. Liver biopsies diagnosed acute alcoholic hepatitis and underlying fibrosis. Liver specimens were processed for messenger RNA (mRNA) levels and various metabolites and were compared with those of six normal controls.
Three patients had cirrhosis, and three had only portal fibrosis. Plasma levels of homocysteine and methionine were increased in two of the three patients with cirrhosis but not in the patients with fibrosis. All patients had markedly lower plasma GSH levels (mean +/- SD: 0.27 +/- 0.19 microM, which is at least 10-fold lower than the normal range). Hepatic S-adenosylmethionine levels were reduced by 50%, whereas methionine, GSH, and cysteine levels were reduced by 70-80%. The mRNA levels of most enzymes involved in methionine metabolism and GSH synthesis were decreased, whereas albumin expression was unchanged. Despite the well known induction of cytochrome P450 2E1 in chronic alcoholics, its mRNA levels were nearly 70% lower in these patients.
In alcoholic hepatitis, abnormal hepatic gene expression in methionine and GSH metabolism occurs and often contributes to decreased hepatic methionine, S-adenosylmethionine, cysteine, and GSH levels. It may be important to replenish these thiols in patients hospitalized with alcoholic hepatitis.
在喂食乙醇的动物和晚期肝硬化患者中会出现蛋氨酸代谢异常。这些异常的预期后果包括肝脏S-腺苷甲硫氨酸和谷胱甘肽（GSH）水平降低、转甲基作用受损以及同型半胱氨酸分解代谢减少，导致肝硬化患者中经常观察到的高同型半胱氨酸血症。在病情较轻的酒精性肝病患者中，尚未同时对这些参数进行检测。
对6例因酒精性肝炎住院的患者进行研究。分析血浆中的同型半胱氨酸、蛋氨酸和GSH水平。肝活检诊断为急性酒精性肝炎和潜在纤维化。对肝标本进行信使核糖核酸（mRNA）水平及各种代谢物检测，并与6例正常对照者的标本进行比较。
3例患者患有肝硬化，3例仅有门脉纤维化。3例肝硬化患者中有2例血浆同型半胱氨酸和蛋氨酸水平升高，而纤维化患者中未升高。所有患者的血浆GSH水平均显著降低（均值±标准差：0.27±0.19微摩尔，至少比正常范围低10倍）。肝脏S-腺苷甲硫氨酸水平降低了50%，而蛋氨酸、GSH和半胱氨酸水平降低了70%-80%。参与蛋氨酸代谢和GSH合成的大多数酶的mRNA水平降低，而白蛋白表达未改变。尽管已知慢性酒精中毒患者细胞色素P450 2E1会被诱导，但这些患者中其mRNA水平降低了近70%。
在酒精性肝炎中，会出现肝脏蛋氨酸和GSH代谢的基因表达异常，且常常导致肝脏蛋氨酸、S-腺苷甲硫氨酸、半胱氨酸和GSH水平降低。对于因酒精性肝炎住院的患者补充这些硫醇可能很重要。
