Finkelstein J D, Martin J J
J Biol Chem. 1986 Feb 5;261(4):1582-7.
We conducted a systematic evaluation of the effects of increasing levels of dietary methionine on the metabolites and enzymes of methionine metabolism in rat liver. Significant decreases in hepatic concentrations of betaine and serine occurred when the dietary methionine was raised from 0.3 to 1.0%. We observed increased concentrations of S-adenosylhomocysteine in livers of rats fed 1.5% methionine and of S-adenosylmethionine and methionine only when the diet contained 3.0% methionine. Methionine supplementation resulted in decreased hepatic levels of methyltetrahydrofolate-homocysteine methyltransferase and increased levels of methionine adenosyltransferase, betaine-homocysteine methyltransferase, and cystathionine synthase. We used these data to simulate the regulatory locus formed by the enzymes which metabolize homocysteine in livers of rats fed 0.3% methionine, 1.5% methionine, and 3.0% methionine. In comparison to the model for the 0.3% methionine diet group, the model for the 3.0% methionine animals demonstrates a 12-fold increase in the synthesis of cystathionine, a 150% increase in flow through the betaine reaction, and a 550% increase in total metabolism of homocysteine. The concentrations of substrates and other metabolites are significant determinants of this apparent adaptation.
我们对膳食蛋氨酸水平升高对大鼠肝脏蛋氨酸代谢的代谢产物和酶的影响进行了系统评估。当膳食蛋氨酸从0.3%提高到1.0%时，肝脏中甜菜碱和丝氨酸的浓度显著降低。我们观察到，仅在饮食中蛋氨酸含量为3.0%时，喂食1.5%蛋氨酸的大鼠肝脏中S-腺苷同型半胱氨酸浓度升高，而S-腺苷甲硫氨酸和蛋氨酸浓度升高。补充蛋氨酸导致肝脏中甲基四氢叶酸-同型半胱氨酸甲基转移酶水平降低，而蛋氨酸腺苷转移酶、甜菜碱-同型半胱氨酸甲基转移酶和胱硫醚合酶水平升高。我们利用这些数据模拟了喂食0.3%蛋氨酸、1.5%蛋氨酸和3.0%蛋氨酸的大鼠肝脏中代谢同型半胱氨酸的酶形成的调控位点。与0.3%蛋氨酸饮食组的模型相比，3.0%蛋氨酸动物的模型显示胱硫醚合成增加了12倍，通过甜菜碱反应的通量增加了150%，同型半胱氨酸的总代谢增加了550%。底物和其他代谢产物的浓度是这种明显适应性的重要决定因素。
