TY - JOUR T1 - De novo acetate production is coupled to central carbon metabolism in mammals JF - bioRxiv DO - 10.1101/259523 SP - 259523 AU - Xiaojing Liu AU - Daniel E. Cooper AU - Ahmad A. Cluntun AU - Marc O. Warmoes AU - Steven Zhao AU - Michael A. Reid AU - Juan Liu AU - Kathryn E. Wellen AU - David G. Kirsch AU - Jason W. Locasale Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/02/04/259523.abstract N2 - In cases of nutritional excess, there is incomplete catabolism of a nutritional source and secretion of a waste product (overflow metabolism), such as the conversion of glucose to lactate (the Warburg Effect) in tumors. Here we report that excess glucose metabolism generates acetate, a key nutrient whose source has been unclear. Conversion of pyruvate, the product of glycolysis, to acetate occurs through two mechanisms: 1) coupling to reactive oxygen species (ROS), and 2) a neomorphic enzyme activity from keto acid dehydrogenases that enable it to function as a pyruvate decarboxylase. Furthermore, we demonstrate that glucose-derived acetate is sufficient to maintain acetyl-coenzyme A (Ac-CoA) pools and cell proliferation in certain limited metabolic environments such as during mitochondrial dysfunction or ATP citrate lyase (ACLY) deficiency. Thus, de novo acetate production is coupled to the activity of central carbon metabolism providing possible regulatory mechanisms and links to pathophysiology. ER -