Shorter term and longer term regulation of pyruvate dehydrogenase kinases

Abstract

The mitochondrial PDH complex of animal tissues catalyses the non reversible conversion of pyruvate to acetyl CoA with concomitant reduction of NADH. The reaction connects glycolysis to oxidative metabolism, and to FFA synthesis, resulting in the irretrievable loss of glucose carbon (animals lack the means of converting acetylCoA to glucose). Some cells in the central nervous system are critically dependent upon glucose oxidation for survival and conservation of glucose by substitution of lipid fuels in cells able to oxidise them is of vital importance during carbohydrate deprivation. Regulation of the PDH complex is therefore of crucial importance in glucose homeostasis.