Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias.
Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias.
复制标题
DOI：
10.1155/2016/9210408
复制
发表时间：
2016
影响因子：
--
通讯作者：
Caterino M
中科院分区：
文献类型：
--
作者：
Imperlini E;Santorelli L;Orrù S;Scolamiero E;Ruoppolo M;Caterino M
有机酸代谢障碍（Organic Acideficiency，OAs）是由氨基酸、碳水化合物或脂质代谢酶活性缺乏引起的遗传性代谢障碍。这些病症导致单羧酸、二羧酸或三羧酸（通常称为有机酸）的积累。OA结局可能涉及不同的器官和/或系统。如果及时诊断和治疗，一些OA疾病很容易管理，而在其他情况下，如丙酸代谢相关的OA（丙酸血症，PA;甲基丙二酸血症，MMA），饮食，维生素治疗和肝移植似乎都不能预防多器官损害。在这里，我们回顾了最近的事态发展，解剖的分子基础的OAs使用整合质谱（MS）为基础的代谢组学和蛋白质组学的策略。基于MS的技术促进了对各种体液中的广谱代谢物的快速和经济的评估，也收集在小样本中，如干燥的血斑。这种方法能够及时诊断OAs，从而促进早期治疗干预。除了提供一个概述MS为基础的方法最常用于研究OA病理生理学的分子机制，我们讨论的主要挑战，代谢组学和蛋白质组学的应用，OA。
Organic acidemias (OAs) are inherited metabolic disorders caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders result in the accumulation of mono-, di-, or tricarboxylic acids, generally referred to as organic acids. The OA outcomes can involve different organs and/or systems. Some OA disorders are easily managed if promptly diagnosed and treated, whereas, in others cases, such as propionate metabolism-related OAs (propionic acidemia, PA; methylmalonic acidemia, MMA), neither diet, vitamin therapy, nor liver transplantation appears to prevent multiorgan impairment. Here, we review the recent developments in dissecting molecular bases of OAs by using integration of mass spectrometry- (MS-) based metabolomic and proteomic strategies. MS-based techniques have facilitated the rapid and economical evaluation of a broad spectrum of metabolites in various body fluids, also collected in small samples, like dried blood spots. This approach has enabled the timely diagnosis of OAs, thereby facilitating early therapeutic intervention. Besides providing an overview of MS-based approaches most frequently used to study the molecular mechanisms underlying OA pathophysiology, we discuss the principal challenges of metabolomic and proteomic applications to OAs.