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丁酸在正常结肠和溃疡性结肠炎中的代谢动力学:底物浓度和肉碱对β-氧化途径的影响。

Kinetics of butyrate metabolism in the normal colon and in ulcerative colitis: the effects of substrate concentration and carnitine on the β-oxidation pathway.

机构信息

Translational Research Center for Gastrointestinal Disorders, KULeuven, Belgium.

出版信息

Aliment Pharmacol Ther. 2011 Sep;34(5):526-32. doi: 10.1111/j.1365-2036.2011.04757.x. Epub 2011 Jun 26.

Abstract

BACKGROUND

Butyrate, a colonic metabolite of carbohydrates, is considered as the major energy source for the colonic mucosa. An impaired butyrate metabolism has been reported in ulcerative colitis (UC), however, the cause still remains unknown.

AIM

In the present study, we investigated whether higher butyrate concentrations could normalise the oxidation rate in UC. Furthermore, it was investigated whether carnitine could enhance the butyrate oxidation.

METHODS

Mucosal biopsies from a total of 26 UC patients and 25 controls were incubated with (14)C-labelled Na-butyrate and the produced (14)CO(2) was measured. First, the rate of oxidative metabolism was compared at three different concentrations of Na-butyrate (0.05 mm, 1 mm and 10 mm). Then, incubations of biopsies were performed with carnitine alone or combined with ATP.

RESULTS

Overall, butyrate oxidation in UC was significantly lower than that in controls. The maximum rate of butyrate oxidation was achieved in UC and control subjects from 1 mm onwards. Increasing the butyrate concentration to a level to be present in the colonic lumen, i.e. 10 mm, did not increase the rate of butyrate oxidation in UC to the rate observed in controls. Addition of carnitine alone or combined with ATP caused no effects.

CONCLUSIONS

Saturation of butyrate kinetics was achieved from 1 mm in UC and control subjects. The rate of butyrate metabolism was significantly impaired in active ulcerative colitis. The addition of compounds interfering with the β-oxidation pathway had no effect on the butyrate metabolism in UC.

摘要

背景

丁酸盐是碳水化合物在结肠中的代谢产物,被认为是结肠黏膜的主要能量来源。溃疡性结肠炎(UC)患者的丁酸盐代谢受损,但具体原因仍不清楚。

目的

本研究旨在探讨较高的丁酸盐浓度是否能使 UC 患者的氧化速率正常化,并研究肉碱是否能增强丁酸盐的氧化。

方法

共对 26 例 UC 患者和 25 例对照者的黏膜活检组织进行(14)C 标记的 Na-丁酸盐孵育,并测量产生的(14)CO2。首先,在 3 种不同 Na-丁酸盐浓度(0.05 mm、1 mm 和 10 mm)下比较氧化代谢率。然后,单独用肉碱或与 ATP 联合孵育活检组织。

结果

UC 患者的丁酸盐氧化总体上明显低于对照组。UC 和对照组患者的丁酸盐氧化最大速率均在 1 mm 以上达到。将丁酸盐浓度增加到结肠腔中存在的水平(即 10 mm),并不能使 UC 患者的丁酸盐氧化速率增加到对照组观察到的水平。单独添加肉碱或与 ATP 联合添加均无作用。

结论

UC 和对照组患者的丁酸盐动力学达到饱和浓度为 1 mm。活性溃疡性结肠炎患者的丁酸盐代谢明显受损。添加干扰β-氧化途径的化合物对 UC 中的丁酸盐代谢没有影响。

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