Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux.
Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux.
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代谢酶的乙酰化协调碳源利用和代谢通量
DOI：
10.1126/science.1179687
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发表时间：
2010-02-19
期刊：
影响因子：
--
通讯作者：
Zhao GP
中科院分区：
文献类型：
--
作者：
Wang Q;Zhang Y;Yang C;Xiong H;Lin Y;Yao J;Li H;Xie L;Zhao W;Yao Y;Ning ZB;Zeng R;Xiong Y;Guan KL;Zhao S;Zhao GP
通过乙酰化共价修饰核内各种蛋白质赖氨酸残基的代谢调节是一种公认的转录控制机制。现在有两篇论文表明，乙酰化可能是控制代谢酶功能的重要调节机制（见Norvell和McMahon的观点）。Zhao等（p. 1000）发现人肝细胞中各种代谢途径中的很大一部分酶被乙酰化。乙酰化通过不同的机制调节各种酶，直接激活一些，抑制一个，控制另一个的稳定性。乙酰化对代谢的控制似乎是进化上保守的：Wang等人（p. 1004）发现肠沙门氏菌在不同碳源上优化生长的能力需要关键代谢酶的不同乙酰化，从而通过代谢途径控制通量。代谢酶的可逆乙酰化有助于细菌适应食物资源的变化。赖氨酸乙酰化调节许多真核生物的细胞过程，但其在原核生物中的功能在很大程度上是未知的。我们证明了沙门氏菌的中心代谢酶在不同碳源下广泛而不同地乙酰化，同时伴随着细胞生长和代谢通量的变化。控制糖酵解和糖异生方向的关键酶的相对活性以及柠檬酸循环和乙醛酸旁路的分支都受到乙酰化的调节。这种调节主要由赖氨酸乙酰转移酶和去乙酰化酶对控制，其表达与生长状态协调。代谢酶的可逆乙酰化确保细胞通过迅速感知细胞能量状态和灵活改变反应速率或方向来响应环境变化。它代表了一种从细菌到哺乳动物的代谢调节机制。
Metabolic Regulation Through Acetylation Covalent modification of lysine residues in various proteins in the nucleus is a recognized mechanism for control of transcription. Now two papers suggest that acetylation may represent an important regulatory mechanism controlling the function of metabolic enzymes (see the Perspective by Norvell and McMahon). Zhao et al. (p. 1000) found that a large proportion of enzymes in various metabolic pathways were acetylated in human liver cells. Acetylation regulated various enzymes by distinct mechanisms, directly activating some, inhibiting one, and controlling the stability of another. Control of metabolism by acetylation appears to be evolutionarily conserved: Wang et al. (p. 1004) found that the ability of the bacterium Salmonella entericum to optimize growth on distinct carbon sources required differential acetylation of key metabolic enzymes, thus controlling flux through metabolic pathways. Reversible acetylation of metabolic enzymes helps bacteria adjust to changes in food resources. Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. We demonstrated that central metabolism enzymes in Salmonella were acetylated extensively and differentially in response to different carbon sources, concomitantly with changes in cell growth and metabolic flux. The relative activities of key enzymes controlling the direction of glycolysis versus gluconeogenesis and the branching between citrate cycle and glyoxylate bypass were all regulated by acetylation. This modulation is mainly controlled by a pair of lysine acetyltransferase and deacetylase, whose expressions are coordinated with growth status. Reversible acetylation of metabolic enzymes ensure that cells respond environmental changes via promptly sensing cellular energy status and flexibly altering reaction rates or directions. It represents a metabolic regulatory mechanism conserved from bacteria to mammals.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
7
作者：
Zhang, Junmei;Sprung, Robert;Zhao, Yingming
通讯作者：
Zhao, Yingming
影响因子：
30.8
作者：
Bereshchenko, OR;Gu, W;Dalla-Favera, R
通讯作者：
Dalla-Favera, R
影响因子：
64.5
作者：
Lin YY;Lu JY;Zhang J;Walter W;Dang W;Wan J;Tao SC;Qian J;Zhao Y;Boeke JD;Berger SL;Zhu H
通讯作者：
Zhu H
DOI：
10.1126/science.1179689
发表时间：
2010-02-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zhao S;Xu W;Jiang W;Yu W;Lin Y;Zhang T;Yao J;Zhou L;Zeng Y;Li H;Li Y;Shi J;An W;Hancock SM;He F;Qin L;Chin J;Yang P;Chen X;Lei Q;Xiong Y;Guan KL
通讯作者：
Guan KL