Figure 11. Schematic illustration of the potential benefits and risks of a GKA stimulation of hepatic glycolysis.
On the left-hand side are listed the potential benefits (i.e. glycogen synthesis, ammonia detoxification and improved energy balance), and on the right-hand side are given the potential risks of GKA (lactic acidosis, lipogenesis and the possibility of triglyceride accumulation in the liver). +, stimulation and/or increased generation; −, inhibition and/or decreased generation. The present findings demonstrate that the stimulation of glycolysis by GKA resulted in numerous changes in normal hepatic metabolism, including: (i) enhanced direct pathway of glycogen synthesis, but decreased gluconeogenesis; (ii) augmented anaplerosis and, associated with this, increased flux through the TCA cycle and generation of glutamate, aspartate or citrate (cataplerosis); (iii) the increased flux through the TCA may enhance the generation of NADH and thus ATP synthesis, resulting in an improved hepatic phosphorylation potential and energetic state; (iv) stimulated synthesis of NAG, and enhanced detoxification of NH3 through ureagenesis; (v) increased generation and output of lactate, which could lead to lactic acidosis; and (vi) increased levels of citrate may augment hepatic lipogenesis and thus accumulation of triglycerides. OXA, oxaloacetate.