THE ROLE OF METHIONINE IN REGULATING FOLATE-DEPENDENT REACTIONS IN ISOLATED RAT HEPATOCYTES
THE ROLE OF METHIONINE IN REGULATING FOLATE-DEPENDENT REACTIONS IN ISOLATED RAT HEPATOCYTES
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DOI：
10.1016/0003-9861(81)90129-6
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发表时间：
1981-01-01
影响因子：
3.9
通讯作者：
TEPHLY, TR
中科院分区：
文献类型：
--
作者：
BILLINGS, RE;NOKER, PE;TEPHLY, TR
在分离的大鼠肝细胞中，组氨酸和甲酸通过叶酸依赖的反应被氧化成二氧化碳。加入l-蛋氨酸，dl-同型半胱氨酸，S-腺苷-L-蛋氨酸(ADO-Met)，ORS-腺苷-L-同型半胱氨酸(ADO-Hcy)可使这些反应刺激两到四倍。这些化合物均能增加肝细胞内Ado-Met和Ado-Hcy的浓度。肝儿茶酚O-甲基转移酶的底物，如L-多巴甲酯和3，4-二羟基苯乙酸，在有或没有添加甲硫氨酸或同型半胱氨酸的情况下，可降低肝细胞的腺苷-蛋氨酸浓度。儿茶酚不影响Ado-Hcy的浓度，但对甲酸和组氨酸的氧化有抑制作用。因此，组氨酸和甲酸氧化速率与Ado-Met浓度之间有很好的正相关性。这些反应的速率与Ado-Hcy的浓度或Ado-Met/Ado-Hcy的浓度比均无相关性。Ado-Hcy可逆转ADO-Met对大鼠肝脏5，10-亚甲基四氢叶酸还原酶的抑制作用，但不改变大鼠肝脏5-甲基四氢叶酸-同型半胱氨酸转甲基酶活性对Ado-Met的依赖性。这些结果表明，蛋氨酸通过转化为Ado-Met，通过增加蛋氨酸合成酶的活性来调节离体肝细胞的叶酸依赖反应，从而导致四氢叶酸浓度的增加。蛋氨酸和Ado-Met增加肝细胞中非甲基四氢叶酸化合物的浓度，降低肝细胞中5-甲基四氢叶酸的浓度，支持这一假说。
In isolated rat hepatocytes, histidine and formate, are oxidized to CO2by folate-dependent reactions. These reactions are stimulated two- to fourfold by the addition ofl-methionine,dl-homocysteine,S-adenosyl-l-methionine (Ado-Met), orS-adenosyl-l-homocysteine (Ado-Hcy). These compounds all increase the hepatocyte concentration of Ado-Met and Ado-Hcy. Substrates of hepatic catecholO-methyltransferase, such asl-Dopa methyl ester and 3,4-dihydroxyphenylacetic acid, decrease the hepatocyte concentration of Ado-Met in the presence or absence of addedl-methionine ordl-homocysteine. The catechols do not affect the concentration of Ado-Hcy, but they inhibit the oxidation of formate and histidine. Thus, there is an excellent positive correlation between the rate of histidine and formate oxidation and the concentration of Ado-Met. There is no correlation between the rate of these reactions and either the Ado-Hcy concentration or the concentration ratio of Ado-Met:Ado-Hcy. Ado-Met inhibition of rat hepatic 5,10-methylene tetrahydrofolate reductase activity is reversed by Ado-Hcy, but the dependency of rat hepatic 5-methyltetrahydrofolate-homocysteine transmethylase activity (methionine synthetase) on Ado-Met is not altered by Ado-Hcy. These results indicate that methionine, through its conversion to Ado-Met, regulates folate-dependent reactions in isolated hepatocytes by increasing activity of methionine synthetase which leads to an increased concentration of tetrahydrofolate. That methionine and Ado-Met increase the hepatocyte concentration of nonmethyltetrahydrofolate compounds and decrease the hepatocyte concentration of 5-methyltetrahydrofolate supports this hypothesis.