Barak A J, Beckenhauer H C, Junnila M, Tuma D J
Department of Veterans Affairs Medical Center, Omaha, Nebraska 68105.
Alcohol Clin Exp Res. 1993 Jun;17(3):552-5. doi: 10.1111/j.1530-0277.1993.tb00798.x.
Previous studies have shown that ethanol feeding to rats alters methionine metabolism by decreasing the activity of methionine synthetase. This is the enzyme that converts homocysteine in the presence of vitamin B12 and N5-methyltetrahydrofolate to methionine. The action of the ethanol results in an increase in the hepatic level of the substrate N5-methyltetrahydrofolate but as an adaptive mechanism, betaine homocysteine methyltransferase, is induced in order to maintain hepatic S-adenosylmethionine at normal levels. Continued ethanol feeding, beyond 2 months, however, produces depressed levels of hepatic S-adenosylmethionine. Because betaine homocysteine methyltransferase is induced in the livers of ethanol-fed rats, this study was conducted to determine what effect the feeding of betaine, a substrate of betaine homocysteine methyltransferase, has on methionine metabolism in control and ethanol-fed animals. Control and ethanol-fed rats were given both betaine-lacking and betaine-containing liquid diets for 4 weeks, and parameters of methionine metabolism were measured. These measurements demonstrated that betaine administration doubled the hepatic levels of S-adenosylmethionine in control animals and increased by 4-fold the levels of hepatic S-adenosylmethionine in the ethanol-fed rats. The ethanol-induced infiltration of triglycerides in the liver was also reduced by the feeding of betaine to the ethanol-fed animals. These results indicate that betaine administration has the capacity to elevate hepatic S-adenosylmethionine and to prevent the ethanol-induced fatty liver.
先前的研究表明，给大鼠喂食乙醇会通过降低甲硫氨酸合成酶的活性来改变甲硫氨酸代谢。甲硫氨酸合成酶是一种在维生素B12和N5-甲基四氢叶酸存在的情况下将同型半胱氨酸转化为甲硫氨酸的酶。乙醇的作用导致底物N5-甲基四氢叶酸的肝脏水平升高，但作为一种适应性机制，甜菜碱同型半胱氨酸甲基转移酶被诱导，以便将肝脏S-腺苷甲硫氨酸维持在正常水平。然而，持续喂食乙醇超过2个月会导致肝脏S-腺苷甲硫氨酸水平降低。由于在喂食乙醇的大鼠肝脏中诱导了甜菜碱同型半胱氨酸甲基转移酶，因此进行了这项研究，以确定喂食甜菜碱（甜菜碱同型半胱氨酸甲基转移酶的一种底物）对对照动物和喂食乙醇动物的甲硫氨酸代谢有何影响。给对照大鼠和喂食乙醇的大鼠分别喂食缺乏甜菜碱和含有甜菜碱的液体饲料4周，并测量甲硫氨酸代谢参数。这些测量结果表明，给予甜菜碱使对照动物肝脏中S-腺苷甲硫氨酸水平增加了一倍，并使喂食乙醇的大鼠肝脏中S-腺苷甲硫氨酸水平增加了4倍。给喂食乙醇的动物喂食甜菜碱还减少了乙醇诱导的肝脏甘油三酯浸润。这些结果表明，给予甜菜碱有能力提高肝脏S-腺苷甲硫氨酸水平并预防乙醇诱导的脂肪肝。
