生物
生物化学
柠檬酸循环
新陈代谢
乙酰辅酶A
糖酵解
脂肪生成
ATP柠檬酸裂解酶
柠檬酸合酶
线粒体
丙酮酸脱氢酶复合物
酶
作者
Xiaojing Liu,Daniel E. Cooper,Ahmad A. Cluntun,Marc O. Warmoes,Steven Zhao,Michael A. Reid,Juan Liu,Peder J. Lund,Mariana Lopes,Benjamin A. García,Kathryn E. Wellen,David G. Kirsch,Jason W. Locasale
出处
期刊:Cell
[Elsevier]
日期:2018-10-01
卷期号:175 (2): 502-513.e13
被引量:265
标识
DOI:10.1016/j.cell.2018.08.040
摘要
Acetate is a major nutrient that supports acetyl-coenzyme A (Ac-CoA) metabolism and thus lipogenesis and protein acetylation. However, its source is 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 the context 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. By virtue of de novo acetate production being coupled to mitochondrial metabolism, there are numerous possible regulatory mechanisms and links to pathophysiology.
科研通智能强力驱动
Strongly Powered by AbleSci AI