Regulation of intestinal lactase in adult hypolactasia.
Regulation of intestinal lactase in adult hypolactasia.
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成人低乳糖酶症中肠道乳糖酶的调节。
DOI：
10.1172/jci115616
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Mantei,N
中科院分区：
文献类型：
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作者：
Lloyd,M;Mevissen,G;Fischer,M;Olsen,W;Goodspeed,D;Genini,M;Boll,W;Semenza,G;Mantei,N
成年期肠道乳糖酶活性相对缺乏，即成人乳糖酶缺乏症，是世界范围内的常见疾病。我们研究了调节乳糖酶根皮苷水解酶在正常和成人hypolactasic科目相关的转录丰度在肠活检与相对合成率的蛋白质在培养的肠外植体。在六个主题的代谢标记研究后，前体乳糖酶根皮苷水解酶的量成正比的酶的比活性，这表明肠道乳糖酶的水平是由合成速率调节。从这些受试者和三名参与先前生物合成研究的低乳糖成人的活检中提取总肠RNA。转录水平显着降低，在缺陷的主题谁表现出减少乳糖酶根皮苷水解酶的合成。测定了两名乳糖分泌不足受试者和两名对照者的乳糖酶-根皮苷水解酶基因5 ′-侧翼区的1 kb序列。未发现序列变异性可解释两组间mRNA水平或生物合成速率的差异。一个单一的hypolactasic主题先前的特点是表现出延迟翻译后处理，显示其他缺陷和控制之间的消息水平。这些结果表明，在我们的大多数受试者中，翻译前机制是近端肠道乳糖酶-根皮苷水解酶表达的主要调控机制。图片
Relative deficiency of intestinal lactase activity during adulthood, adult hypolactasia, is a common condition worldwide. We studied the regulation of lactase-phlorizin hydrolase in normal and adult hypolactasic subjects by correlating transcript abundance in intestinal biopsies with relative synthetic rates for the protein in cultured intestinal explants. After metabolic labelling studies in six subjects, precursor lactase-phlorizin hydrolase was identified in amounts directly proportional to the enzyme-specific activity suggesting that levels of intestinal lactase are regulated by synthetic rate. Total intestinal RNA was extracted from biopsies of these subjects and three hypolactasic adults who had participated in previous biosynthesis studies. Transcript levels were markedly reduced in deficient subjects who demonstrated diminished lactase-phlorizin hydrolase synthesis. The sequence of 1 kb of 5'-flanking region of the lactase-phlorizin hydrolase gene was determined in two hypolactasic subjects and two controls. No sequence variability was identified to account for differences in mRNA levels or biosynthetic rates between the two groups. A single hypolactasic subject previously characterized as demonstrating delayed posttranslational processing, showed message levels intermediate between other deficients and controls. These results suggest that in the majority of our subjects, pretranslational mechanisms account for the predominate regulatory control of lactase-phlorizin hydrolase expression in the proximal intestine.Images