EFFECT OF DIETARY METHYL-GROUP DEFICIENCY ON FOLATE METABOLISM IN RATS

EFFECT OF DIETARY METHYL-GROUP DEFICIENCY ON FOLATE METABOLISM IN RATS
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DOI:
10.1093/jn/119.4.618
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发表时间:
1989-04-01
影响因子:
4.2
通讯作者:
WAGNER, C
WAGNER, C
中科院分区:
医学2区
文献类型:
--
作者:
HORNE, DW;COOK, RJ;WAGNER, C

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缺乏甲基的氨基酸饮食的致癌作用归因于细胞甲基化反应的改变。这些饮食不含胆碱,蛋氨酸被同型半胱氨酸取代。因此,蛋氨酸生物合成所需的所有甲基,以及随后形成的s -腺苷蛋氨酸和多胺,都必须利用叶酸依赖的单碳单元还原来重新形成。在喂食缺乏甲基饮食的大鼠中,肝脏总叶酸水平明显下降。这种下降在个别形式的叶酸水平上很明显:10-HCO-H4folate, 5-HCO-H4folate, 5-CH3-H4folate和H4folate。然而,5- ch3 - h4叶酸在总叶酸池中所占的比例并没有改变,直到给大鼠喂食缺乏甲基的食物4周后,才出现增加。在将缺乏甲基的大鼠换成含有蛋氨酸和胆碱的营养充足的对照饮食后,所有数值都迅速逆转。叶酸用于甲基生物合成的增加可能是肝脏中叶酸流失的原因。
The carcinogenic effects of methyl-deficient, amino acid-defined diets have been attributed to alterations in cellular methylation reactions. These diets contain no choline, and methionine is replaced by homocysteine. Hence, all methyl groups needed for methionine biosynthesis with subsequent formation of S-adenosylmethionine and polyamines must be formed de novo utilizing folate-dependent reduction of one-carbon units. In rats fed the methyl-deficient diet, there was a marked decrease in total liver folate levels. This decrease was apparent in the levels of the individual forms of folate: 10-HCO-H4folate, 5-HCO-H4folate, 5-CH3-H4folate and H4folate. The percent of the total folate pool made up by 5-CH3-H4folate did not change, however, until after the rats had been fed the methyl-deficient diet for 4 wk, and then an increase was seen. After the methyl-deficient rats were switched to a nutritionally adequate control diet containing methionine and choline, all values rapidly reversed. Increased use of folate for methyl group biosynthesis may be responsible for the loss of folates from the liver.