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Analysis of the regulation of surfactant phosphatidylcholine metabolism using stable isotopes

机译:使用稳定同位素来分析表面活性剂磷脂酰胆碱代谢的调节

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The pathways and mechanisms that regulate pulmonary surfactant synthesis, processing, secretion and catabolism have been extensively characterised using classical biochemical and analytical approaches. These have constructed a model, largely in experimental animals, for surfactant phospholipid metabolism in the alveolar epithelial cell whereby phospholipid synthesised on the endoplasmic reticulum is selectively transported to lamellar body storage vesicles, where it is subsequently processed before secretion into the alveolus. Surfactant phospholipid is a complex mixture of individual molecular species defined by the combination of esterified fatty acid groups and a comprehensive description of surfactant phospholipid metabolism requires consideration of the interactions between such molecular species. However, until recently, lipid analytical techniques have not kept pace with the considerable advances in understanding of the enzymology and molecular biology of surfactant metabolism. Refinements in electrospray ionisation mass spectrometry (ESI-MS) can now provide very sensitive platforms for the rapid characterisation of surfactant phospholipid composition in molecular detail. The combination of ESI-MS and administration of phospholipid substrates labelled with stable isotopes extends this analytical approach to the quantification of synthesis and turnover of individual molecular species of surfactant phospholipid. As this methodology does not involve radioactivity, it is ideally suited to application in clinical studies. This review will provide an overview of the metabolic processes that regulate the molecular specificity of surfactant phosphatidylcholine together with examples of how the application of stable isotope technologies in vivo has, for the first time, begun to explore regulation of the molecular specificity of surfactant synthesis in human subjects. (C) 2017 Elsevier GmbH. All rights reserved.
机译:通过经典的生物化学和分析方法广泛地表征调节肺表面活性剂合成,加工,分泌和分解代谢的途径和机制。这些已经构建了一种模型,主要是实验动物,用于肺泡上皮细胞中的表面活性剂磷脂代谢,由此在内质网上合成的磷脂被选择性地运送到层状体储存囊泡,在分泌到肺泡之前,随后将其加工。表面活性剂磷脂是通过酯化脂肪酸基团的组合而定义的个体分子物种的复杂混合物,并且表面活性剂磷脂代谢的综合描述需要考虑这些分子种类之间的相互作用。然而,直到最近,脂质分析技术尚未与对表面活性剂代谢的酶学和分子生物学的理解相当大的进步保持同步。电喷雾电离质谱(ESI-MS)的改进现在可以为分子细节的表面活性剂磷脂组合物的快速表征提供非常敏感的平台。 ESI-MS和用稳定同位素标记的磷脂底物的组合延伸了这种分析方法,以定量表面活性剂磷脂的单个分子种类的合成和转单。由于这种方法不涉及放射性,因此非常适合在临床研究中应用。本综述概述了调节表面活性剂磷脂酰胆碱的分子特异性的代谢过程以及第一次开始稳定同位素技术的应用程序的实施例开始探讨表面活性剂合成的分子特异性的调节人类受试者。 (c)2017 Elsevier GmbH。版权所有。

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