Chapter 15 (abbreviated): Principles of Metabolic Regulation

1. Chapter 15 (abbreviated): Principles of Metabolic Regulation CHEM 7784 Biochemistry Professor Bensley

2. CHAPTER 15 (Abbreviated)Principles of Metabolic Regulation Today’s Objectives: (To learn and understand the) • Principles of regulation in biological systems • Glycolysis vs. gluconeogenesis – which one is turned “on” and which one is turned “off”?

4. Homeostasis • Organisms maintain homeostasis by keeping the concentrations of most metabolites at steady state • In steady state, the rate of synthesis of a metabolite equals the rate of breakdown of this metabolite

5. Principles of Regulation • The flow of metabolites through the pathways is regulated to maintain homeostasis • Sometimes, the levels of required metabolites must be altered very rapidly • Need to increase the capacity of glycolysis during the action • Need to reduce the capacity of glycolysis after the action • Need to increase the capacity of gluconeogenesis after successful action

6. Feedback Inhibition • In many cases, ultimate products of metabolic pathways directly or indirectly inhibit their own biosynthetic pathways • ATP inhibits the commitment step of glycolysis

7. Factors that Affect the Activity of Enzymes

8. Some Enzymes in the Pathway Limit the Flux of Metabolites More than Others • Hexokinase and phosphofructokinase are appropriate targets for regulation of glycolytic flux

9. Elasticity Coefficient Measures the Responsiveness to Substrate

10. Control of Glycogen Synthesis • Insulin signaling pathway • increases glucose import into muscle • stimulates the activity of muscle hexokinase • activates glycogen synthase • Increased hexokinase activity enables activation of glucose • Glycogen synthase makes glycogen for energy storage

11. UDP-Glucose

12. Isozymes may Show Different Kinetic Properties • Isozymes are different enzymes that catalyze the same reaction • They typically share similar sequences • Their regulation is often different

13. Glycolysis vs. Gluconeo-genesis

14. Regulation of Phosphofructokinase-1 • The conversion of fructose-6-phosphate to fructose 1,6-bisphosphate is the commitment step in glycolysis • ATP is a negative effector • Do not spend glucose in glycolysis if there is plenty of ATP

15. Regulation of Phosphofructokinase 1 and Fructose 1,6-Bisphosphatase • Go glycolysis if AMP is high and ATP is low • Go gluconeogenesis if AMP is low

16. Regulation by Fructose 2,6-Bisphosphate • F26BP activates phosphofructokinase (glycolytic enzyme) • F26BP inhibits fructose 1,6-bisphosphatase (gluconeogenetic enzyme)

17. Regulation by Fructose 2,6-Bisphosphate • Go glycolysis if F26BP is high • Go gluconeogenesis if F26BP is low

18. Chapter 15: Summary In this chapter, we learned that: • living organisms regulate the flux of metabolites via metabolic pathways by • increasing or decreasing enzyme concentrations • activating or inactivating key enzymes in the pathway • the activity of key enzymes in glycolysis and gluconeogenesis is tightly regulated via various activating and inhibiting metabolites