Rafii Mahroukh, Elango Rajavel, House James D, Courtney-Martin Glenda, Darling Pauline, Fisher Lawrence, Pencharz Paul B
The Research Institute, The Hospital for Sick Children, Ontario, Canada.
J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Oct 15;877(28):3282-91. doi: 10.1016/j.jchromb.2009.05.002. Epub 2009 May 13.
The sulfur amino acids, methionine and cysteine play crucial roles in cells as a substrate for protein synthesis, as a methyl donor, and for the synthesis of sulfur-containing compounds, including the key intracellular tripeptide, glutathione. Homocysteine is an intermediary metabolite formed during the metabolism of methionine to cysteine. Dysregulation of homocysteine metabolism is implicated in adverse clinical outcomes such as increased risk of cardiovascular disease, stroke, Alzheimer's disease dementia and osteoporosis. While hyperhomocysteinemia is commonly observed in those conditions, the impact on other related metabolites is condition-specific. Therefore, there exists a need to establish precise and sensitive analytical techniques that allow for the simultaneous measurement of homocysteine and related metabolites in biological samples. The current review outlines the development and use of liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) to simultaneously measure metabolites involved in sulfur amino acid metabolism. Additionally, extensions of the technique in relation to the measurement of sulfur amino acid and one-carbon kinetics in vivo are discussed. The LC-MS/MS technique has the capacity for unambiguous analyte identification and confirmation, due to its high specificity and sensitivity. It has the greatest potential of being accepted and utilized as a dedicated homocysteine and its related metabolite Standard reference method (SRM).
含硫氨基酸甲硫氨酸和半胱氨酸在细胞中发挥着关键作用，它们是蛋白质合成的底物、甲基供体，还参与含硫化合物的合成，包括关键的细胞内三肽谷胱甘肽。同型半胱氨酸是甲硫氨酸代谢为半胱氨酸过程中形成的中间代谢产物。同型半胱氨酸代谢失调与不良临床后果有关，如心血管疾病、中风、阿尔茨海默病性痴呆和骨质疏松症风险增加。虽然在这些情况下通常会观察到高同型半胱氨酸血症，但对其他相关代谢产物的影响因具体情况而异。因此，需要建立精确且灵敏的分析技术，以便能够同时测量生物样品中的同型半胱氨酸和相关代谢产物。本综述概述了液相色谱电喷雾串联质谱法（LC-MS/MS）的发展及应用，该方法可同时测量参与含硫氨基酸代谢的代谢产物。此外，还讨论了该技术在体内含硫氨基酸和一碳动力学测量方面的扩展。由于其高特异性和灵敏度，LC-MS/MS技术具有明确鉴定和确认分析物的能力。它最有潜力被接受并用作专门的同型半胱氨酸及其相关代谢产物标准参考方法（SRM）。
