去酰化酶SIRT5研究进展.docVIP

去酰化酶SIRT5研究进展 　　[摘要] 长寿因子5（Sirtuin 5），也叫SIRT5，是长寿因子（Sirtuins）家族成员之一。除具有去乙酰化酶活性外，还具有很强的去琥珀酰化、去丙二酰基化及去戊二酰基化活性。现已明确的SIRT5的底物仅有十余种，通过对不同底物发挥相同的酶活性，或对同一底物发挥不同的酶活性，参与调控葡萄糖氧化、脂肪酸氧化、氨解毒等物质代谢和活性氧自由基（ROS）清除、抗凋亡、炎性反应等多种生命活动。SIRT5表达异常与肿瘤的发生及发展密切相关，但其作用尚无定论。SIRT5可促进肿瘤增殖、转移、耐药及代谢重编程，发挥促癌基因作用；也可抑制肿瘤细胞生长和凋亡，发挥抑癌基因作用。此外，SIRT5异常还与肥厚性心肌病和心肌梗塞等心血管疾病，及帕金森病和阿尔兹海默症等神经代谢性疾病密切相关。本文将从SIRT5的结构与调控、酶活性与生物学功能、及SIRT5与疾病的关系等方面进行综述，以全面了解SIRT5的研究现状。 　　[关键词] SIRT5；去乙酰化；去琥珀酰化；去丙二酰基化；去戊二酰基化；肿瘤 　　[中图分类号] R979.1 [文献标识码] A [文章编号] 1673-7210（2018）04（a）-0042-04 　　[Abstract] Sirtuin 5， also called SIRT5， is a member of Sirtuins family. Besides its deacetylation activity， SIRT5 also has strong desuccinylation， demalonylation and deglutarylation activities. Therefore， SIRT5 has been attracted much attention in recent years. Currently， about more than tenproteins were identified as substrates of SIRT5. SIRT5 is involved in the regulation of glucose oxidation， ROS metabolism and fatty acid oxidation， ammonia removal， detoxification， anti apoptosis， inflammation and so on， by playing the same enzymatic activity on different substrates， or playing different enzymatic activity on the same substrate. The abnormal expression of SIRT5 is closely related to the occurrence and development of tumor， though its function is not clarified yet. SIRT5 can play the role of oncogene to promote tumor proliferation， metastasis， drug resistance and metabolic reprogramming. On the other hand， SIRT5 also play the role of tumor suppressor gene to inhibit tumor cell growth and apoptosis. In addition， SIRT5 abnormalities are also closely related to hypertrophic cardiomyopathy， myocardial infarction and other cardiovascular diseases， such as Parkinson′s disease and Alzheimer′s disease. In order to have a good comprehensive on the research progress of SIRT5， this paper reviews the structure and regulation， enzyme activity and biological function of SIRT5， and the relationship between SIRT5 and desease in details here. 　　[Key words]