Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load.
Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load.
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DOI：
10.1093/ajcn.81.2.440
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发表时间：
2005-02
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影响因子：
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通讯作者：
K. da Costa;Christopher E. Gaffney;L. Fischer;S. Zeisel
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文献类型：
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作者：
K. da Costa;Christopher E. Gaffney;L. Fischer;S. Zeisel
背景技术血液中同型半胱氨酸浓度升高可能是动脉粥样硬化发生的独立危险因素。同型半胱氨酸浓度升高可能是由于同型半胱氨酸形成蛋氨酸的甲基化减少所致，如叶酸缺乏症中所发生的情况。同型半胱氨酸的甲基化存在一条平行途径，其中胆碱通过甜菜碱作为甲基供体。目的 我们的目标是确定胆碱缺乏是否会导致同型半胱氨酸甲基化能力下降。设计 C57BL/6J 小鼠喂食含有 0、10 或 35 mmol 胆碱/kg 饮食的饮食 3 周。然后我们给动物口服甲硫氨酸并测量血浆同型半胱氨酸浓度。此外，在一项初步研究中，我们检查了 8 名男性，他们的饮食每天每 70 公斤体重提供 550 毫克胆碱，持续 10 天，然后饮食几乎不提供胆碱，直到临床判断受试者胆碱缺乏或持续时间<或=42 天。在每个饮食阶段结束时施用蛋氨酸负荷。结果 蛋氨酸负荷两小时后，缺乏胆碱的小鼠血浆同型半胱氨酸浓度是胆碱喂养小鼠的两倍。蛋氨酸负荷后 4 小时，临床上胆碱耗尽的男性血浆同型半胱氨酸浓度比胆碱未耗尽的男性高 35%。结论 这些结果表明，胆碱与叶酸一样，在人体同型半胱氨酸的代谢中发挥着重要作用，并且在评估胆碱营养时，对蛋氨酸负荷的反应可能有用。
BACKGROUND Elevated concentrations of homocysteine in blood may be an independent risk factor for the development of atherosclerosis. Elevated homocysteine concentrations can be caused by decreased methylation of homocysteine to form methionine, as occurs in folate deficiency. A parallel pathway exists for methylation of homocysteine, in which choline, by way of betaine, is the methyl donor. OBJECTIVE Our goal was to determine whether choline deficiency results in a decreased capacity to methylate homocysteine. DESIGN C57BL/6J mice were fed diets containing 0, 10, or 35 mmol choline/kg diet for 3 wk. We then administered an oral methionine load to the animals and measured plasma homocysteine concentrations. Also, in a pilot study, we examined 8 men who were fed a diet providing 550 mg choline/d per 70 kg body weight for 10 d, followed by a diet providing almost no choline, until the subjects were clinically judged to be choline deficient or for <or=42 d. A methionine load was administered at the end of each dietary phase. RESULTS Two hours after the methionine load, choline-deficient mice had plasma homocysteine concentrations twice those of choline-fed mice. Four hours after the methionine load, clinically choline-depleted men had plasma homocysteine concentrations that were 35% greater than those in men not choline depleted. CONCLUSION These results suggest that choline, like folate, plays an important role in the metabolism of homocysteine in humans and that response to a methionine load may be useful when assessing choline nutriture.