Studies on the absorption and metabolism of folic acid. I. Folate absorption in the dog after exposure of isolated intestinal segments to synthetic pteroylpolyglutamates of various chain lengths.

Studies on the absorption and metabolism of folic acid. I. Folate absorption in the dog after exposure of isolated intestinal segments to synthetic pteroylpolyglutamates of various chain lengths.
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叶酸吸收和代谢的研究。

DOI:
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发表时间:
1971
影响因子:
15.9
通讯作者:
C. Butterworth
C. Butterworth
中科院分区:
医学1区
文献类型:
--
作者:
C. Baugh;C. Krumdieck;H. J. Baker;C. Butterworth

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通过测定从含有游离叶酸和/或已知链长的蝶酰聚谷氨酸盐的分离肠段中流出的静脉血中叶酸的量和化学性质,研究了麻醉犬的叶酸吸收。置于管腔中的色谱纯测试材料是通过明确的固相合成方法制备的。该合成过程不仅产生已知结构的化合物,还提供了一种使γ谷氨酰链中任何给定位置的谷氨酸残基具有放射性的方法。例如,蝶蝶呤(蝶酰三谷氨酸)的合成方式是(14)C仅存在于中间的谷氨酸单元中。适当放置标签可以评估肽裂解的程度。氯化铜抑制血浆结合酶的作用。通过干酪乳杆菌和粪链球菌测定、柱色谱法以及蝶啶结合放射性的定量测量来分析血浆样品。据观察,具有生物活性的叶酸出现在肠系膜静脉中,其中翼酰单、二、三、五或七谷氨酸出现在管腔中。一般来说,吸收率似乎与γ谷氨酰侧链的长度成反比。当等摩尔量的两种物质同时置于单个肠段中时,循环中出现的叶酸(3)H 标记的蝶酰单谷氨酸大约是(14)C 标记的蝶酰五谷氨酸的两倍。蝶酰单谷氨酸似乎是从每个测试的前体进入血液的主要形式。然而,获得的证据表明,将翼酰二或三谷氨酸放入管腔后,翼酰二谷氨酸可能很快进入肠系膜静脉,但较高级的聚谷氨酸则不会。放射性和生物活性模式的比较表明,在通过肠粘膜的前 30 分钟内,几乎没有转化为还原或甲基化形式(如果有的话)。我们的结论是,蝶酰单谷氨酸和蝶酰二谷氨酸都可以穿过狗的肠粘膜,并且还原和甲基化对于吸收过程不是必需的。
Folic acid absorption was studied in anesthetized dogs by determining the amount and chemical nature of folate in venous blood emerging from isolated intestinal segments containing free folic acid and/or pteroylpolyglutamates of a known chain length. Chromatographically pure test materials placed in the lumen were prepared by unambiguous solid phase synthetic methods. This synthetic procedure not only yields compounds of known structure, it also provides a means by which glutamic acid residues at any given position in the gamma glutamyl chain can be made radioactive. For example, teropterin (pteroyltriglutamate) was synthesized in such a way that (14)C was present only in the middle glutamic acid unit. Suitable placement of label permitted assessment of the extent of peptide cleavage. The action of plasma conjugase was inhibited by copper chloride. Plasma samples were analyzed by Lactobacillus casei and Streptococcus faecalis assay, by column chromatography, and by quantitative measurement of pteridine-bound radioactivity. It was observed that biologically active folate appeared in the mesenteric vein with either pteroylmono-, di-, tri-, penta-, or heptaglutamate in the lumen. Generally speaking the absorption rate appeared to be inversely related to the length of the gamma glutamyl side chain. Roughly twice as much folic acid appeared in the circulation from (3)H-labeled pteroylmonoglutamate as from (14)C-labeled pteroylpentaglutamate when equimolar amounts of each were placed simultaneously in a single intestinal segment. Pteroylmonoglutamate appeared to be the predominant form entering the blood from each of the precursors tested. However, evidence was obtained that pteroyldiglutamate may enter the mesenteric vein soon after placing pteroyldi-, or triglutamate in the lumen, but not with the higher polyglutamates. Comparison of radioactivity and biological activity patterns suggests little conversion, if any, to reduced or methylated forms during the first 30 min of passage through the intestinal mucosa. We conclude that both pteroylmonoglutamates and pteroyldiglutamates may across the intestinal mucosa of the dog, and that reduction and methylation are not essential to the absorption process.