S-adenosylmethionine in liver health, injury, and cancer.
S-adenosylmethionine in liver health, injury, and cancer.
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DOI：
10.1152/physrev.00047.2011
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发表时间：
2012-10
影响因子：
33.6
通讯作者：
Mato JM
中科院分区：
文献类型：
--
作者：
Lu SC;Mato JM
S-腺苷蛋氨酸(ADOMet，又称腺苷蛋氨酸，SAM等)是哺乳动物细胞合成的主要生物甲基供体，但在肝脏中含量最高。ADOMet的生物合成需要蛋氨酸腺苷转移酶(MAT)。在哺乳动物中，有两个基因编码MAT，一个是在正常肝脏中主要表达的MAT1A，另一个是在所有肝外组织中表达的MAT2A。慢性肝病患者MAT活性和ADOMet水平降低。缺乏Mat1a的小鼠肝脏ADOMet水平降低，并发展为氧化应激、脂肪性肝炎和肝细胞癌(HCC)。在这些小鼠中，一些信号通路异常，这可能有助于肝细胞癌的形成。然而，如果肝脏ADOMet水平长期过高，也会发生损伤和肝细胞癌。这可能是由于甘氨酸N-甲基转移酶(GNMT)的非活性突变造成的。携带GNMT突变的儿童肝脏转氨酶升高，GNMT基因敲除小鼠出现肝损伤、纤维化和肝细胞癌。因此，正常的肝脏ADOMet水平对于维持肝脏健康、预防损伤和肝细胞癌是必要的。ADOMet对妊娠期胆汁淤积症有效，它在其他人类肝病中的作用还有待更好的确定。在实验模型中，它在肝癌和其他形式的癌症中作为化学预防药物是有效的。
S-adenosylmethionine (AdoMet, also known as SAM and SAMe) is the principal biological methyl donor synthesized in all mammalian cells but most abundantly in the liver. Biosynthesis of AdoMet requires the enzyme methionine adenosyltransferase (MAT). In mammals, two genes, MAT1A that is largely expressed by normal liver and MAT2A that is expressed by all extrahepatic tissues, encode MAT. Patients with chronic liver disease have reduced MAT activity and AdoMet levels. Mice lacking Mat1a have reduced hepatic AdoMet levels and develop oxidative stress, steatohepatitis, and hepatocellular carcinoma (HCC). In these mice, several signaling pathways are abnormal that can contribute to HCC formation. However, injury and HCC also occur if hepatic AdoMet level is excessive chronically. This can result from inactive mutation of the enzyme glycine N-methyltransferase (GNMT). Children with GNMT mutation have elevated liver transaminases, and Gnmt knockout mice develop liver injury, fibrosis, and HCC. Thus a normal hepatic AdoMet level is necessary to maintain liver health and prevent injury and HCC. AdoMet is effective in cholestasis of pregnancy, and its role in other human liver diseases remains to be better defined. In experimental models, it is effective as a chemopreventive agent in HCC and perhaps other forms of cancer as well.
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DOI：
10.1152/ajpgi.00332.2009
发表时间：
2010-05-01
影响因子：
4.5
作者：
Andringa, Kelly K.;King, Adrienne L.;Bailey, Shannon M.
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DOI：
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发表时间：
1987-12-30
期刊：
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影响因子：
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作者：
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通讯作者：
ALEMANY, S
影响因子：
13.5
作者：
Ara, Ainhoa Iglesias;Xia, Meng;Lu, Shelly C.
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DOI：
10.1016/j.biocel.2003.11.016
发表时间：
2004-11-01
影响因子：
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作者：
Avila, MA;García-Trevijano, ER;Mato, JM
通讯作者：
Mato, JM