Discovery of Cell-Type-Specific and Disease-Related Enzymatic Activity Changes via Global Evaluation of Peptide Metabolism
Discovery of Cell-Type-Specific and Disease-Related Enzymatic Activity Changes via Global Evaluation of Peptide Metabolism
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DOI：
10.1021/jacs.6b11376
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发表时间：
2017-03-08
影响因子：
15
通讯作者：
Urano, Yasuteru
中科院分区：
文献类型：
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作者：
Onagi, Jun;Komatsu, Toru;Urano, Yasuteru
细胞动态平衡是由一个复杂的反应网络维持的，该网络由大量的酶活动(酶)催化，这些酶活动决定了细胞的表型。在这里，我们重点介绍了蛋白酶和多肽酶的酶组学，因为这些酶是一类重要的疾病相关蛋白。我们描述了一个系统，它(A)使用一系列外源多肽底物同时评估多肽的代谢活性，(B)高通量地识别代谢特定多肽底物的酶。我们证实，开发的系统能够发现特定细胞类型和疾病相关的外肽酶和内肽酶活性，并识别负责的酶。例如，我们发现在人类结直肠肿瘤组织样本中，内肽酶神经溶素的活性高度升高。这一简单而强大的酶组学平台将广泛应用于揭示各种疾病状态下具有生物标志物或药物靶点潜在价值的细胞类型特异性反应和酶功能改变，并研究其潜在的病理机制。
Cellular homeostasis is maintained by a complex network of reactions catalyzed by enormous numbers of enzymatic activities (the enzymome), which serve to determine the phenotypes of cells. Here, we focused on the enzymomics of proteases and peptidases because these enzymes are an important class of disease-related proteins. We describe a system that (A) simultaneously evaluates metabolic activities of peptides using a series of exogenous peptide substrates and (B) identifies the enzymes that metabolize the specified peptide substrate with high throughput. We confirmed that the developed system was able to discover cell-type-specific and disease-related exo-and endopeptidase activities and identify the responsible enzymes. For example, we found that the activity of the endopeptidase neurolysin is highly elevated in human colorectal tumor tissue samples. This simple but powerful enzymomics platform should be widely applicable to uncover cell-type-specific reactions and altered enzymatic functions with potential value as biomarkers or drug targets in various disease states and to investigate the mechanisms of the underlying pathologies.