Simplified Chinese: 药学上具吸引力的肿瘤促进剂/抑制剂SIRT5的赖氨酸去丙酰化底物的特异性并未完全澄清。本研究重新分析了公开数据，并通过生物信息学的应用程序GeneMania（3.5.2）在Cytoscape（3.9.1）环境下预测了潜在的药用有意义的结果。野生型和ob/ob（肥胖型糖尿病前期）小鼠中的SIRT5甲酰化组进行了通路富集和基因功能预测分析。 在野生型小鼠中的分析显示SIRT5甲酰化在真核翻译延长(ETE；节点EF1A1、EEF2、EEF1D和EEF1G)，氨基酸及衍生物代谢(AADM)和硒氨基酸代谢(SAM)中的参与。SIRT5的肿瘤促进/抑制剂活性通过包括AADM(GLUD1、SHMT1、ACAT1)中的肿瘤促进底物，以及参与AADM和SAM(ALDH9A1、BHMT、GNMT)的肿瘤抑制底物来介导。硒刺激SIRT5和其他sirtuins的表达。SIRT5反过来调节硒半胱氨酸合成，形成一个调节环。在糖尿病前期ob/ob小鼠中，SIRT5甲酰化组的分析确定了mTORC1通路是促进SIRT5功能的机制。SIRT5甲酰化组、琥珀酰化组和戊二酰化组的结果比较揭示了几个差异。分析表明了除了控制葡萄糖代谢外，SIRT5甲酰化还有其他方面的功能，定义了几个独特的底物和通路，并显示出与SIRT5其他酶活性的差异，这些差异可以用于药物治疗的益处。 版权所有©2023 Elsevier Inc. 发行。

The specificity of the lysine demalonylation substrates of the pharmaceutically attractive tumor promoter/suppressor SIRT5 is not comprehensively clarified. The present study re-analyses publicly available data and highlights potentially pharmaceutically interesting outcomes by the use of bioinformatics.The interaction networks of SIRT5 malonylome from the wild-type and ob/ob (obese pre-diabetic type) mice were subjected to the pathway enrichment and gene function prediction analysis using GeneMania (3.5.2) application run under Cytoscape (3.9.1) environment.The analysis in the wild-type mice revealed the involvement of SIRT5 malonylome in Eukaryotic translation elongation (ETE; the nodes EF1A1, EEF2, EEF1D, and EEF1G), Amino acid and derivative metabolism (AADM), and Selenoamino acid metabolism (SAM). The tumor promoter/suppressor activity of SIRT5 is mediated through the tumor promoter substrates included in AADM (GLUD1, SHMT1, ACAT1), and the tumor suppressor substrates involved in AADM and SAM (ALDH9A1, BHMT, GNMT). Selen stimulates the expression of SIRT5 and other sirtuins. SIRT5 in turn regulates the selenocysteine synthesis, which creates a regulatory loop. The analysis of SIRT5 malonylome in pre-diabetic ob/ob mice identifies the mTORC1 pathway as a mechanism, which facilitates SIRT5 functions. The comparison of the outcomes of SIRT5 malonylome, succinylome, and glutarylome analysis disclosed several differences.The analysis showed additional aspects of SIRT5 malonylome functions besides the control of glucose metabolism. It defined several unique substrates and pathways, and it showed differences compared to other enzymatic activities of SIRT5, which could be used for pharmaceutical benefits.Copyright © 2023. Published by Elsevier Inc.