Acetate Revisited: A Key Biomolecule at the Nexus of Metabolism, Epigenetics, and Oncogenesis - Part 2: Acetate and ACSS2 in Health and Disease.
Acetate Revisited: A Key Biomolecule at the Nexus of Metabolism, Epigenetics, and Oncogenesis - Part 2: Acetate and ACSS2 in Health and Disease.
复制标题
DOI：
10.3389/fphys.2020.580171
复制
发表时间：
2020
影响因子：
4
通讯作者：
Namboodiri AM
中科院分区：
文献类型：
--
作者：
Moffett JR;Puthillathu N;Vengilote R;Jaworski DM;Namboodiri AM
醋酸酯是最短的链脂肪酸，无论它是来自饮食还是来自肠道中纤维的微生物发酵，都被认为是有益健康的。这些对健康的益处广泛，从改善心脏功能到增强红细胞生成和记忆形成。了解醋酸盐如何影响如此多不同的生物功能现在是一个深入研究的领域。蛋白质乙酰化是最常见的翻译后修饰之一，而全身醋酸酯的增加强烈地推动了蛋白质乙酰化。由于乙酰化几乎影响每一类蛋白质的活性，醋酸盐导致的信号和基因转录变化与包括癌症在内的几种常见人类疾病有关。在这篇综述的第二部分中，我们将重点介绍醋酸盐在健康和人类疾病中扮演的一些角色。醋酸酯激活酶酰辅酶A短链合成酶家族成员2(ACSS2)将是这一焦点的主要组成部分，因为它在调节中枢代谢和应激反应的靶向蛋白质乙酰化反应中发挥作用。ACSS2是目前已知的唯一一种可以在细胞质和细胞核中回收脱乙酰基反应产生的醋酸盐的酶，包括蛋白质和代谢物脱乙酰基反应。因此，ACSS2可以回收组蛋白脱乙酰基酶反应和sirtuins介导的蛋白质脱乙酰基反应所产生的醋酸盐等。值得注意的是，ACSS2可以激活从乙酰化代谢物释放的醋酸盐，包括N-乙酰天冬氨酸(NAA)，这是人脑中浓度最高的乙酰化代谢物。NAA与癌细胞的代谢再编程有关，ACSS2也在其中发挥作用。在这里，我们讨论了醋酸盐在健康和疾病中可以扮演的特定背景的角色。
Acetate, the shortest chain fatty acid, has been implicated in providing health benefits whether it is derived from the diet or is generated from microbial fermentation of fiber in the gut. These health benefits range widely from improved cardiac function to enhanced red blood cell generation and memory formation. Understanding how acetate could influence so many disparate biological functions is now an area of intensive research. Protein acetylation is one of the most common post-translational modifications and increased systemic acetate strongly drives protein acetylation. By virtue of acetylation impacting the activity of virtually every class of protein, acetate driven alterations in signaling and gene transcription have been associated with several common human diseases, including cancer. In part 2 of this review, we will focus on some of the roles that acetate plays in health and human disease. The acetate-activating enzyme acyl-CoA short-chain synthetase family member 2 (ACSS2) will be a major part of that focus due to its role in targeted protein acetylation reactions that can regulate central metabolism and stress responses. ACSS2 is the only known enzyme that can recycle acetate derived from deacetylation reactions in the cytoplasm and nucleus of cells, including both protein and metabolite deacetylation reactions. As such, ACSS2 can recycle acetate derived from histone deacetylase reactions as well as protein deacetylation reactions mediated by sirtuins, among many others. Notably, ACSS2 can activate acetate released from acetylated metabolites including N-acetylaspartate (NAA), the most concentrated acetylated metabolite in the human brain. NAA has been associated with the metabolic reprograming of cancer cells, where ACSS2 also plays a role. Here, we discuss the context-specific roles that acetate can play in health and disease.
登录
查看更多内容
影响因子：
9.3
作者：
Brissette CA;Houdek HM;Floden AM;Rosenberger TA
通讯作者：
Rosenberger TA
影响因子：
4.2
作者：
Bhatt DP;Houdek HM;Watt JA;Rosenberger TA
通讯作者：
Rosenberger TA
影响因子：
4.7
作者：
Arun, Peethambaran;Madhavarao, Chikkathur N.;Namboodiri, M. A. Aryan
通讯作者：
Namboodiri, M. A. Aryan
影响因子：
4.8
作者：
Brown, AJ;Goldsworthy, SM;Dowell, SJ
通讯作者：
Dowell, SJ
影响因子：
7.5
作者：
Bae, Jeong Mo;Kim, Jung Ho;Kang, Gyeong Hoon
通讯作者：
Kang, Gyeong Hoon