Cheng F W, Shane B, Stokstad E L
Br J Haematol. 1975 Nov;31(3):323-36. doi: 10.1111/j.1365-2141.1975.tb00863.x.
The effects of dietary vitamin B12 and methionine deficiency, and the in vitro addition of methionine, homocysteine, or folic acid on the methylation of dUMP to dTMP were studied in rat bone marrow culture. Vitamin B12 or methionine deficiency had no effect on the methylation reaction or on bone marrow folate levels although the vitamin B12 content in bone marrow was reduced in vitamin B12 deficiency. In vitro addition of vitamin B12 or folic acid also had no effect on the methylation of dUMP. In vitro addition of methionine reduced the methylation of dUMP and increased the proportion of 5-methyltetrahydrofolate at the expense of other folate coenzymes. The reason for this 'anti-folate' effect of methionine, which is the opposite to that found in liver, was not clear. The presence of 5,10-methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase were confirmed in rat bone marrow and they were inhibited by S-adenosylmethionine and methionine, respectively, in a similar fashion to that found with the liver enzymes. Homocysteine had no effect on the proportions of the various folate coenzymes in bone marrow but did inhibit the incorporation of deoxyuridine and deoxythymidine into DNA. It appeared that homocysteine exerted at a non-folate dependent step beyond the formation of dTMP.
在大鼠骨髓培养中，研究了饮食中维生素B12和蛋氨酸缺乏，以及体外添加蛋氨酸、同型半胱氨酸或叶酸对dUMP甲基化生成dTMP的影响。维生素B12或蛋氨酸缺乏对甲基化反应或骨髓叶酸水平没有影响，尽管维生素B12缺乏时骨髓中的维生素B12含量降低。体外添加维生素B12或叶酸对dUMP的甲基化也没有影响。体外添加蛋氨酸会降低dUMP的甲基化，并增加5-甲基四氢叶酸的比例，同时其他叶酸辅酶的比例会相应减少。蛋氨酸这种“抗叶酸”作用的原因尚不清楚，这与在肝脏中发现的情况相反。在大鼠骨髓中证实存在5,10-亚甲基四氢叶酸还原酶和5-甲基四氢叶酸-同型半胱氨酸甲基转移酶，它们分别被S-腺苷甲硫氨酸和蛋氨酸抑制，其方式与肝脏中的酶类似。同型半胱氨酸对骨髓中各种叶酸辅酶的比例没有影响，但会抑制脱氧尿苷和脱氧胸苷掺入DNA。似乎同型半胱氨酸在dTMP形成之后的一个非叶酸依赖步骤发挥作用。
