Isotopomer spectral analysis of intermediates of cholesterol synthesis in human subjects and hepatic cells.
Isotopomer spectral analysis of intermediates of cholesterol synthesis in human subjects and hepatic cells.
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人类受试者和肝细胞中胆固醇合成中间体的同位素异构体光谱分析。
DOI：
10.1152/ajpendo.00324.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Kelleher,JK
中科院分区：
文献类型：
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作者：
Lindenthal,B;Aldaghlas,TA;Holleran,AL;Sudhop,T;Berthold,HK;VonBergmann,K;Kelleher,JK
胆固醇合成途径的类固醇中间体的特征在于相对于胆固醇的快速周转率，这是由于它们的小池大小。由于小池将标记迅速，这些中间体可以提供有价值的信息纳入同位素从头合成胆固醇和相关化合物。通过同位素光谱分析（伊萨），在人体和肝细胞模型中研究了[1- 13 C]乙酸酯胆固醇合成中间体的标记。在人类受试者中，将[1- 13 C]乙酸盐注入十二指肠12小时表明，约50%的血浆胆甾醇池来自此间隔期间的从头合成。脂肪生成乙酰辅酶A前体库富集在输注开始的3小时内达到恒定值。体外研究表明，当胆固醇合成被他汀类药物或含胆固醇的血清抑制时，肝细胞模型会降低脂甾醇的从头合成。我们提出了一种新的计算，以增加胆固醇合成的准确性和精密度估计在体内结合伊萨的脂甾醇和胆固醇。
Steroid intermediates of the cholesterol synthesis pathway are characterized by rapid turnover rates relative to cholesterol due to their small pool size. Because the small pools will label rapidly, these intermediates may provide valuable information about the incorporation of isotopes in de novo synthesis of cholesterol and related compounds. The labeling of cholesterol synthesis intermediates from [1-13C]acetate was investigated in human subjects and in liver cell models by means of isotopomer spectral analysis (ISA). In human subjects, infusing [1-13C]acetate into the duodenum for 12 h demonstrated that ∼50% of the plasma lathosterol pool was derived from de novo synthesis during this interval. The lipogenic acetyl-CoA precursor pool enrichment reached a constant value within 3 h of the start of the infusion. In vitro studies indicated that liver cell models decrease de novo lathosterol synthesis when cholesterol synthesis is inhibited by statins or cholesterol-containing serum. We propose a new calculation to increase the accuracy and precision of cholesterol synthesis estimates in vivo combining the ISA of lathosterol and cholesterol.