Division of Neonatology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands.
Mass Spectrom Rev. 2012 Mar-Apr;31(2):312-30. doi: 10.1002/mas.20344. Epub 2011 Jul 18.
The use of stable isotopes combined with mass spectrometry (MS) provides insight into metabolic processes within the body. Herein, an overview on the relevance of stable isotope methodology in pediatric research is presented. Applications for the use of stable isotopes with MS cover carbohydrate, fat, and amino acid metabolism as well as body composition, energy expenditure, and the synthesis of specific peptides and proteins, such as glutathione and albumin. The main focus of these studies is on the interactions between nutrients and the endogenous metabolism within the body and how these factors affect the health of a growing infant. Considering that the early imprinting of metabolic processes hugely impacts metabolism (and thus functional outcome) later in life, research in this area is important and is advancing rapidly. The major fluxes on a metabolic level are the synthesis and breakdown rates. They can be quantified using kinetic tracer analysis and mathematical modeling. Organic MS and isotope ratio mass spectrometry (IRMS) are the two most mature techniques for the isotopic analysis of compounds. Introduction of the samples is usually done by coupling gas chromatography (GC) to either IRMS or MS because it is the most robust technique for specific isotopic analysis of volatile compounds. In addition, liquid chromatography (LC) is now being used more often as a tool for sample introduction of both volatile and non-volatile compounds into IRMS or MS for (13)C isotopic analyses at natural abundances and for (13)C-labeled enriched compounds. The availability of samples is often limited in pediatric patients. Therefore, sample size restriction is important when developing new methods. Also, the availability of stable isotope-labeled substrates is necessary for measurements of the kinetics and concentrations in metabolic studies, which can be a limiting factor. During the last decade, the availability of these substrates has increased. Furthermore, improvements in the accuracy, precision, and sensitivity of existing techniques (such as GC/IRMS) and the development of new techniques (such as LC/IRMS) have opened up new avenues for tackling these limitations.
稳定同位素与质谱联用为研究体内代谢过程提供了新的视角。本文对稳定同位素方法在儿科研究中的应用进行了综述。稳定同位素与 MS 联用的应用涵盖了碳水化合物、脂肪和氨基酸代谢以及身体成分、能量消耗和特定肽和蛋白质（如谷胱甘肽和白蛋白）的合成。这些研究的主要重点是营养素与体内内源性代谢之间的相互作用以及这些因素如何影响生长中婴儿的健康。考虑到代谢过程的早期印记对生命后期的代谢（进而对功能结果）有巨大影响，因此该领域的研究非常重要，并且发展迅速。代谢水平上的主要通量是合成和分解速率。可以使用动力学示踪剂分析和数学建模来定量它们。有机 MS 和同位素比质谱（IRMS）是化合物同位素分析最成熟的两种技术。样品的引入通常通过将气相色谱（GC）与 IRMS 或 MS 耦合来完成，因为这是对挥发性化合物进行特定同位素分析最可靠的技术。此外，现在越来越多地使用液相色谱（LC）作为将挥发性和非挥发性化合物引入 IRMS 或 MS 以进行（13）C 自然丰度同位素分析和（13）C 标记富集化合物的工具。儿科患者的样品通常有限。因此，在开发新方法时，样品量的限制很重要。此外，稳定同位素标记底物的可用性对于代谢研究中的动力学和浓度测量是必要的，这可能是一个限制因素。在过去十年中，这些底物的可用性有所增加。此外，现有技术（如 GC/IRMS）的准确性、精密度和灵敏度的提高以及新技术（如 LC/IRMS）的开发为解决这些限制提供了新的途径。
