生物化学原理教学（杨荣武）Regulation of CHO Metabolism.pptVIP

Chapter 11 Regulation of glycolysis Regulation of Hexokinase Regulation of PFK-1 Regulation of PFK-1 by Fructose 2,6-bisphosphate (F2,6BP) Effect of glucagon on liver glycolysis Regulation of Pyruvate Kinase The Pasteur Effect * 1. When ATP levels are sufficient, glycolysis activity decreases Hexokinase inhibited by excess glucose 6-phosphate PFK-1 is inhibited by ATP and citrate Pyruvate kinase is inhibited by ATP 2. When ATP is needed, glycolysis is activated AMP (the product of ATP consumption) relieve the inhibition of PFK-1 by ATP Fructose 2,6-bisphosphate (F2,6BP) relieve the inhibition of PFK-1 by ATP Pyruvate kinase is activated by F1,6BP Step 1 Step 3 Step 10 Hexokinase reaction is metabolically irreversible G6P (product) levels increase when?glycolysis is inhibited at sites further along in the pathway G6P inhibits hexokinase isozymes I, II and III that are active at normal glucose concentrations (Km values ~10-6 to 10-4M) Glucokinase (hexokinase IV, Km ~10-2M) forms G6P in the liver (for glycogen synthesis) when glucose is abundant (activity is modulated by fructose phosphates and a regulatory protein) ATP is a substrate and an allosteric inhibitor of PFK-1 AMP allosterically activates PFK-1 by relieving the ATP inhibition (ADP is also an activator in mammalian systems) Changes in AMP and ADP concentrations can control the flux through PFK-1 Elevated levels of citrate (indicate ample substrates for citric acid cycle) also inhibit PFK-1 F2,6-BP is a potent activator of PFK-1 F2,6-BP is formed from F6P by phosphofructokinase-2 (PFK-2), which is a bi-functional enzyme b-D-Fructose 2,6-bisphosphate Formation and hydrolysis of F2,6-BP Hormone glucagon is released from the pancreas when blood glucose levels are low PFK-2 is bi-functional Glucagon slows glycolysis Glucagon induces glucose synthesis and conversion to glucose from glycogen Four PK isozymes exist in mammalian tissues PK is allosterically activated by F1,6BP, inhibited by ATP Glucagon s