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牛磺酸缺乏的猫中,存在线粒体 tRNA 牛磺酸修饰和胆汁酸牛磺酸结合缺陷的胆汁酸代谢障碍。

Impaired bile acid metabolism with defectives of mitochondrial-tRNA taurine modification and bile acid taurine conjugation in the taurine depleted cats.

机构信息

Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Ibaraki, 300-0395, Japan.

Ibaraki Prefectural University of Health Sciences, Ibaraki, 300-0394, Japan.

出版信息

Sci Rep. 2020 Mar 18;10(1):4915. doi: 10.1038/s41598-020-61821-6.

Abstract

Taurine that conjugates with bile acid (BA) and mitochondrial-tRNA (mt-tRNA) is a conditional essential amino acid in humans, similarly to cats. To better understand the influence of acquired depletion of taurine on BA metabolism, the profiling of BAs and its intermediates, BA metabolism-enzyme expression, and taurine modified mt-tRNAs were evaluated in the taurine deficient diet-supplemented cats. In the taurine depleted cats, taurine-conjugated bile acids in bile and taurine-modified mt-tRNA in liver were significantly decreased, whereas unconjugated BA in serum was markedly increased. Impaired bile acid metabolism in the liver was induced accompanied with the decreases of mitochondrial cholesterol 27-hydroxylase expression and mitochondrial activity. Consequently, total bile acid concentration in bile was significantly decreased by the low activity of mitochondrial bile acid synthesis. These results implied that the insufficient dietary taurine intake causes impaired bile acid metabolism, and in turn, a risk for the various diseases similar to the mitochondrial diseases would be enhanced.

摘要

牛磺酸与胆汁酸(BA)和线粒体 tRNA(mt-tRNA)结合,是人类和猫等动物的条件必需氨基酸。为了更好地理解牛磺酸获得性缺乏对 BA 代谢的影响,本研究在补充牛磺酸缺乏饮食的猫中,对 BA 及其中间产物进行了分析、BA 代谢酶的表达以及牛磺酸修饰的 mt-tRNA。在牛磺酸缺乏的猫中,胆汁中的牛磺酸结合胆汁酸和肝脏中的牛磺酸修饰 mt-tRNA 明显减少,而血清中的未结合 BA 则明显增加。肝内胆汁酸代谢受损,伴随着线粒体胆固醇 27-羟化酶表达和线粒体活性的降低。因此,由于线粒体胆汁酸合成活性降低,胆汁中的总胆汁酸浓度显著降低。这些结果表明,膳食中牛磺酸摄入不足会导致胆汁酸代谢紊乱,进而增加各种疾病的风险,类似于线粒体疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e2d/7080809/a895bc7f22a5/41598_2020_61821_Fig1_HTML.jpg

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