1. Lecture 14

2. Metabolism Biochem = Series of coordinated reactions Reaction kinetics = Thermodynamics, enzyme kinetics General principles of metabolic regulation Glycolysis – reactions, energy

3. Key regulatory points of Glycolysis

6. “Signaling” to regulate metabolism Low Gluose - Where? - Brain response? - Liver response? How to coordinate? Differential responses?

7. Roles of different organs in metabolism library.med.utah.edu Master regulator www2.univet.hu Hormonal control www.myfitnessstudio.co.uk Some regulation

8. Selfish! Roles of different organs in metabolism www.udel.edu science.nationalgeographic.com

9. “Signaling” to Glycolysis Example 1: Pyruvate kinase Low blood sugar = ? Glycolysis (in liver) Low blood sugar = Secrete ? ? (in liver) = Phosphorylate PK PK-PO 4 = ? activity What about in brain?

10. “Signaling” to Glycolysis Example 1: Pyruvate kinase High blood sugar = ? Glycolysis (in liver) High blood sugar = Secrete ? ? (in liver) = ? PK PK = ? activity What about in brain?

11. “Signaling” in Glycolysis Example 1: Pyruvate kinase

12. Tissue-specific responses Example 1: Pyruvate kinase High blood sugar Hormone PK LiverBrain glycolysiseffect Low blood sugar Hormone PK LiverBrain glycolysiseffect

13. Fru 2,6-bis-PO 4 regulates Glycolysis

15. “Signaling” to Glycolysis Example 2: Phosphofructokinase 2 PFK2 : Fru 6-PO4  Fru 2,6 bis-PO4 Fructose bisphosphatase 2 = reverse Fru 6-PO4Fru 2,6 bis-PO4 PFK2 = Fructose bisphosphatase 2 (FBPase2)!

16. “Signaling” to Glycolysis Example 2: Phosphofructokinase 2 Huh? Say what? PFK2 = FBPase2? What determines which activity is active?

17. “Signaling” to Glycolysis – Second messengers Example 2: Phosphofructokinase 2 Remember Glucagon? cAMP activates Protein Kinase A cAMP is a “second messenger” (In liver) Glucagon activates “Adenylate cyclase”

18. Phosphorylation – again! Example 2: Phosphofructokinase 2 Protein Kinase A (PKA) phosphorylates PFK2 PFK2FBPase2 PO 4 Active FBPase2 = ? Glycolysis

19. Example 2: Phosphofructokinase 2

20. Signaling cascade recap LIVER Example 2: Phosphofructokinase 2 Pancreas Low Glc ? ? Fru 2,6 bis-PO4 Adenylate cyclase ? PKA ? ? PFK1 ? GLYCOLYSIS

21. Signaling cascades IMPORTANT means of regulation Across cells Within cells (Nucleus  Mitochondria) Concept of “second messengers”

22. Role of ATP in cells