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首页> 外文期刊>Journal of Lipid Research >Studying apolipoprotein turnover with stable isotope tracers: correct analysis is by modeling enrichments.
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Studying apolipoprotein turnover with stable isotope tracers: correct analysis is by modeling enrichments.

机译:用稳定的同位素示踪剂研究载脂蛋白的更新:正确的分析是通过对富集进行建模。

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摘要

Lipoprotein kinetic parameters are determined from mass spectrometry data after administering mass isotopes of amino acids, which label proteins endogenously. The standard procedure is to model the isotopic content of the labeled precursor amino acid and of proteins of interest as tracer-to-tracee ratio (TTR). It is shown here that even though the administered tracer alters amino acid mass and turnover, apolipoprotein synthesis is unaltered and hence the apolipoprotein system is in a steady state, with the total (labeled plus unlabeled) masses and fluxes remaining constant. The correct model formulation for apolipoprotein kinetics is shown to be in terms of tracer enrichment, not of TTR. The needed mathematical equations are derived. A theoretical error analysis is carried out to calculate the magnitude of error in published results using TTR modeling. It is shown that TTR modeling leads to a consistent underestimation of the fractional synthetic rate. In constant-infusion studies, the bias error percent is shown to equal approximately the plateau enrichment, generally <10%. It is shown that, in bolus studies, the underestimation error can be larger. Thus, for mass isotope studies with endogenous tracers, apolipoproteins are in a steady state and the data should be fitted by modeling enrichments.
机译:在施用氨基酸内源性标记氨基酸的质量同位素后,根据质谱数据确定脂蛋白动力学参数。标准程序是将示踪剂与示踪剂之比(TTR)模拟标记的前体氨基酸和目标蛋白质的同位素含量。在此显示,即使所施用的示踪剂改变了氨基酸质量和周转率,载脂蛋白的合成也没有改变,因此载脂蛋白系统处于稳定状态,总质量(标记的加上未标记的)和通量保持恒定。载脂蛋白动力学的正确模型公式显示为示踪剂富集,而不是TTR。推导出所需的数学方程式。使用TTR建模进行了理论误差分析,以计算已发布结果中的误差大小。结果表明,TTR建模导致分数合成速率的一致低估。在恒定输注研究中,偏倚误差百分比显示近似等于平台富集,通常<10%。结果表明,在推注研究中,低估误差可能更大。因此,对于使用内源示踪剂进行的大规模同位素研究,载脂蛋白处于稳定状态,应通过对模型进行浓缩来拟合数据。

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