Down Regulation of Pyruvate Dehydrogenase Complex in Skeletal Muscle during Sepsis: Implications for Sepsis-Induced Hyperlactatemia

摘要: Sepsis shifts the dynamic metabolic interactions involved in regulation of inter-organ substrate fluxes, and ultimately results derangements plasma concentrations metabolites. One manifestation septic process is development hyperlactatemia absence overt signs hypoperfusion. Lactate end-product glycolysis. Consequently, changes lactate during sepsis may reflect altered glucose metabolism. In skeletal muscle, PDH complex link between glycolytic pathway oxidative tricarboxylic acid cycle activity metabolism glucose. sepsis, production pyruvate via glycolysis accelerated muscle. Because proportion active, nonphosphorylated form diminished preferentially converted to lactate, subsequently released into circulation. The inhibition resides a stimulation kinase sepsis. Although factors responsible for dyshomeostasis are unknown, evidence suggests that TNF functions as proximal mediator.