Acetate Production from Glucose and Coupling to Mitochondrial Metabolism in Mammals.
Acetate Production from Glucose and Coupling to Mitochondrial Metabolism in Mammals.
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DOI：
10.1016/j.cell.2018.08.040
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发表时间：
2018-10-04
期刊：
影响因子：
64.5
通讯作者：
Locasale JW
中科院分区：
文献类型：
--
作者：
Liu X;Cooper DE;Cluntun AA;Warmoes MO;Zhao S;Reid MA;Liu J;Lund PJ;Lopes M;Garcia BA;Wellen KE;Kirsch DG;Locasale JW
醋酸盐是一种主要的营养物质，支持乙酰辅酶A(Ac-CoA)代谢，从而促进脂肪生成和蛋白质乙酰化。然而，它的来源一直不清楚。在这里，我们报道了丙酮酸，糖酵解的最终产物和中枢碳代谢的关键节点，在哺乳动物中定量地产生醋酸酯。这一现象在营养过剩的情况下变得更加明显，例如在葡萄糖代谢过度的情况下。丙酮酸转化为醋酸酯有两种机制：1)与活性氧自由基(ROS)偶联，2)酮酸脱氢酶产生新形酶活性，从而发挥丙酮酸脱羧酶的功能。此外，我们还证明，在有限的代谢环境中，例如在线粒体功能障碍或ATP柠檬酸裂解酶(ACLY)缺乏期间，从头产生醋酸酯可以维持Ac-CoA池和细胞增殖。新醋酸酯的产生存在于哺乳动物中，并进一步与线粒体代谢相结合，提供了可能的调节机制和与病理生理学的联系。细胞通过两种不同的机制直接从丙酮酸合成醋酸酯，在代谢不足的时期为乙酰辅酶A池提供支持
Acetate is a major nutrient that supports acetyl-coenzyme A (Ac-CoA) metabolism and thus lipogenesis and protein acetylation. Its source however has been unclear. Here we report that pyruvate, the end product of glycolysis and key node in central carbon metabolism, quantitatively generates acetate in mammals. This phenomenon becomes more pronounced in contexts of nutritional excess such as during hyperactive glucose metabolism. Conversion of pyruvate to acetate occurs through two mechanisms: 1) coupling to reactive oxygen species (ROS), and 2) neomorphic enzyme activity from keto acid dehydrogenases that enable function as pyruvate decarboxylases. Further, we demonstrate that de novo acetate production sustains Ac-CoA pools and cell proliferation in limited metabolic environments such as during mitochondrial dysfunction or ATP citrate lyase (ACLY) deficiency. De novo acetate production occurs in mammals and is further coupled to mitochondrial metabolism providing possible regulatory mechanisms and links to pathophysiology. Cells produce acetate directly from pyruvate through two distinct mechanisms, providing back up support for acetyl-CoA pools during times of metabolic deficiency
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影响因子：
29
作者：
Lee JV;Carrer A;Shah S;Snyder NW;Wei S;Venneti S;Worth AJ;Yuan ZF;Lim HW;Liu S;Jackson E;Aiello NM;Haas NB;Rebbeck TR;Judkins A;Won KJ;Chodosh LA;Garcia BA;Stanger BZ;Feldman MD;Blair IA;Wellen KE
通讯作者：
Wellen KE
DOI：
10.1016/0005-2760(66)90087-7
发表时间：
1966-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
BREMER, J
通讯作者：
BREMER, J
使用原代人类三维器官培养物进行定量高吞吐量筛选预测体内功效。
影响因子：
16.6
作者：
Kenny, Hilary A.;Lal-Nag, Madhu;White, Erin A.;Shen, Min;Chiang, Chun-Yi;Mitra, Anirban K.;Zhang, Yilin;Curtis, Marion;Schryver, Elizabeth M.;Bettis, Sam;Jadhav, Ajit;Boxer, Matthew B.;Li, Zhuyin;Ferrer, Marc;Lengyel, Ernst
通讯作者：
Lengyel, Ernst
影响因子：
4.1
作者：
Lu Y;Yao D;Chen C
通讯作者：
Chen C
影响因子：
--
作者：
Litzenburger UM;Opitz CA;Sahm F;Rauschenbach KJ;Trump S;Winter M;Ott M;Ochs K;Lutz C;Liu X;Anastasov N;Lehmann I;Höfer T;von Deimling A;Wick W;Platten M
通讯作者：
Platten M