Metabolite profiling for the identification of altered metabolic pathways in Alzheimer's disease
Metabolite profiling for the identification of altered metabolic pathways in Alzheimer's disease
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DOI：
10.1016/j.jpba.2014.10.010
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发表时间：
2015-03-25
影响因子：
3.4
通讯作者：
Luis Gomez-Ariza, Jose
中科院分区：
文献类型：
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作者：
Gonzalez-Dominguez, Raul;Garcia-Barrera, Tamara;Luis Gomez-Ariza, Jose
气相色谱-质谱联用是低分子量代谢物代谢组学分析的最常用工具。它在健康调查中的适用性是毫无疑问的，因为参与代谢的中心途径的初级代谢物通常在疾病中改变。这项工作的目的是调查阿尔茨海默病患者和健康对照之间的血清代谢差异，以阐明疾病的病理机制。检测到23种代谢物水平的变化，包括乳酸、α-酮戊二酸、异柠檬酸、葡萄糖、油酸、腺苷和胆固醇升高，以及尿素、缬氨酸、天冬氨酸、焦谷氨酸、谷氨酰胺、苯丙氨酸、天冬酰胺、鸟氨酸、哌啶酸、组氨酸、酪氨酸、棕榈酸和尿酸、色氨酸、硬脂酸和胱氨酸降低。代谢途径分析揭示了多种受影响的途径，如能量缺乏，氧化应激，高氨血症等。此外，值得注意的是，这些化合物中的一些以前在AD研究中没有描述过，例如α-酮戊二酸、异柠檬酸哌啶酸、焦谷氨酸和腺苷，证实了这种代谢组学方法在寻找用于早期检测阿尔茨海默病的新的潜在标志物中的潜力。(C)2014爱思唯尔有限公司版权所有。
Gas chromatography coupled to mass spectrometry is the most frequent tool for metabolomic profiling of low molecular weight metabolites. Its suitability in health survey is beyond doubt, given that primary metabolites involved in central pathways of metabolism are usually altered in diseases. The objective of this work is to investigate metabolic differences in serum between Alzheimer's disease patients and healthy controls in order to elucidate pathological mechanisms underlying to disease. Alterations in levels of 23 metabolites were detected, including increased lactic acid, a-ketoglutarate, isocitric acid, glucose, oleic acid, adenosine and cholesterol, as well as decreased urea, valine, aspartic acid, pyroglutamate, glutamine, phenylalanine, asparagine, ornithine, pipecolic acid, histidine, tyrosine, palmitic and uric acid, tryptophan, stearic acid and cystine. Metabolic pathway analysis revealed the involvement of multiple affected pathways, such as energy deficiencies, oxidative stress, hyperammonemia, and others. Moreover, it is noteworthy that some of these compounds have not been previously described in AD research, such as a-ketoglutarate, isocitrate pipecolic acid, pyroglutamate and adenosine, confirming the potential of this metabolomic approach in the search of novel potential markers for early detection of Alzheimer's disease. (C) 2014 Elsevier B.V. All rights reserved.