Metabolic Flexibility in Cancer: Targeting the Pyruvate Dehydrogenase Kinase:Pyruvate Dehydrogenase Axis
نویسندگان
چکیده
منابع مشابه
The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility
Metabolic flexibility is the capacity of a system to adjust fuel (primarily glucose and fatty acids) oxidation based on nutrient availability. The ability to alter substrate oxidation in response to nutritional state depends on the genetically influenced balance between oxidation and storage capacities. Competition between fatty acids and glucose for oxidation occurs at the level of the pyruvat...
متن کاملThe Effects of Pyruvate Dehydrogenase Kinase 4 (PDK4) Inhibition on Metabolic Flexibility during Endurance Training in Skeletal Muscles of Streptozotocin-induced Diabetic Rats
Background:Metabolic flexibility is the capacity of a system to adjust fuel (primarily glucose and fatty acids) oxidation based on nutrient availability. Pyruvate Dehydrogenase Kinase 4 (PDK4) is one of the main enzymes that play a critical role in metabolic flexibility. In current study, we examined PDK4 inhibition along with exercise training (ET) on the gene expression of Es...
متن کاملPyruvate dehydrogenase kinase activity of pig heart pyruvate dehydrogenase (E1 component of pyruvate dehydrogenase complex).
The pyruvate dehydrogenase (E1) and acetyltransferase (E2) components of pig heart and ox kidney pyruvate dehydrogenase (PDH) complex were separated and purified. The E1 component was phosphorylated (alpha-chain) and inactivated by MgATP. Phosphorylation was mainly confined to site 1. Addition of E2 accelerated phosphorylation of all three sites in E1 alpha and inactivation of E1. On the basis ...
متن کاملMetabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells
BACKGROUND Pyruvate dehydrogenase (PDH) occupies a central node of intermediary metabolism, converting pyruvate to acetyl-CoA, thus committing carbon derived from glucose to an aerobic fate rather than an anaerobic one. Rapidly proliferating tissues, including human tumors, use PDH to generate energy and macromolecular precursors. However, evidence supports the benefits of constraining maximal ...
متن کاملPyruvate Dehydrogenase Kinase 4
OBJECTIVE Pyruvate dehydrogenase complex (PDC) serves as the metabolic switch between glucose and fatty acid utilization. PDC activity is inhibited by PDC kinase (PDK). PDC shares the same substrate, i.e., pyruvate, as glyceroneogenesis, a pathway controlling fatty acid release from white adipose tissue (WAT). Thiazolidinediones activate glyceroneogenesis. We studied the regulation by rosiglita...
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ژورنال
عنوان ژورنال: Molecular Cancer Therapeutics
سال: 2019
ISSN: 1535-7163,1538-8514
DOI: 10.1158/1535-7163.mct-19-0079