Bills N D, Jones A D, Clifford A J
Department of Nutrition, University of California, Davis 95616.
J Nutr. 1991 Oct;121(10):1643-8. doi: 10.1093/jn/121.10.1643.
Most commercially available tretrahydro and substituted folates are racemic mixtures of R and S isomers about pteridine-carbon 6. Some reports show the unnatural stereoisomers modify specific aspects of folate metabolism, whereas others show no significantly different biologic effects between isomers. The extent to which unnatural folate stereoisomers are inert in vivo is unclear. Possible interactions between isomers at normal dietary folate intakes were tested by comparing growth, liver and serum folate concentrations, and congener patterns of folate-depleted rats fed amino acid-based diets with 283, 566 or 1132 nmol folic acid (standards), or 566 nmol racemic 5-methyltetrahydrofolate, 5-formyltetrahydrofolate or 5,10-diformyltetrahydrofolate/kg diet for 3 wk. Growth and tissue folate levels increased with each increment in dietary folic acid. Growth and liver and serum folate concentrations of rats fed 566 nmol 5-formyltetrahydrofolate or 5-methyltetrahydrofolate/kg diet were similar to those of rats fed 283 nmol folic acid/kg diet. Rats fed 5,10-diformyltetrahydrofolate lost weight and had depressed serum folate levels, and most died. Results show that biologic activity of racemic 5-formyltetrahydrofolate and 5-methyltetrahydrofolate was half that of folic acid, and the R isomer did not affect growth at the levels fed. Addition of a second formyl group destroyed folate bioactivity. The folate-depleted rat model is useful for testing biologic effects of individual folate stereoisomers in vivo as they become commercially available.
大多数市售的四氢叶酸和取代叶酸是围绕蝶啶碳6的R和S异构体的外消旋混合物。一些报告显示，非天然立体异构体可改变叶酸代谢的特定方面，而另一些报告则显示异构体之间的生物学效应无显著差异。非天然叶酸立体异构体在体内的惰性程度尚不清楚。通过比较用283、566或1132 nmol叶酸（标准品）或566 nmol外消旋5-甲基四氢叶酸、5-甲酰基四氢叶酸或5,10-二甲酰基四氢叶酸/kg饲料喂养3周的氨基酸基饮食的叶酸缺乏大鼠的生长、肝脏和血清叶酸浓度以及叶酸同系物模式，测试了正常膳食叶酸摄入量下异构体之间的可能相互作用。随着膳食叶酸的每一次增加，生长和组织叶酸水平都有所提高。用566 nmol 5-甲酰基四氢叶酸或5-甲基四氢叶酸/kg饲料喂养的大鼠的生长、肝脏和血清叶酸浓度与用283 nmol叶酸/kg饲料喂养的大鼠相似。用5,10-二甲酰基四氢叶酸喂养的大鼠体重减轻，血清叶酸水平降低，大多数死亡。结果表明，外消旋5-甲酰基四氢叶酸和5-甲基四氢叶酸的生物活性是叶酸的一半，并且在所喂水平下R异构体不影响生长。添加第二个甲酰基会破坏叶酸的生物活性。叶酸缺乏大鼠模型可用于测试单个叶酸立体异构体在体内的生物学效应，因为它们已上市。
