1. Lecture 14 WEB: Go to pollev.com/ucibio TEXT: Text UCIBIO to 37607
After joining session, text your question

2. Lecture 14 objectives
Apply principles to understand Glycolysis regulation
Understand how regulation of Glycolysis is integrated across organs
Know important signaling pathways that regulate Glycolysis
Understand how signaling integrates Glycolysis regulation

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

4. Key regulatory points of Glycolysis

5. Key regulatory points of Glycolysis

6. Key regulatory points of Glycolysis

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

8. Roles of different organs in metabolism
library.med.utah.edu
www2.univet.hu

9. Roles of different organs in metabolism
science.nationalgeographic.com

10. “Signaling” to Glycolysis
Example 1: Pyruvate kinase
Low blood sugar = ? Glycolysis (in liver)
Low blood sugar = Secrete ?
? (in liver) = Phosphorylate PK
PK-PO4 = ? activity
What about in brain?

11. “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?

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

13. Tissue-specific responses
Example 1: Pyruvate kinase
High blood sugar
Low blood sugar
Hormone Insulin
Hormone Glucagon
Liver
Brain
Liver
Brain
De-PO4 PK
No effect on PK
PO4 PK
No effect on PK
Increase
glycolysis
No glycolytic
effect
Decrease
glycolysis
No glycolytic
effect

14. Fru 2,6-bis-PO4 regulates Glycolysis

15. Fru 2,6-bis-PO4 regulates Glycolysis

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

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

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

19. Phosphorylation – again!
Example 2: Phosphofructokinase 2
Protein Kinase A (PKA) phosphorylates PFK2
PFK2
FBPase2
PO4
Active FBPase2 = ? Glycolysis

20. Example 2: Phosphofructokinase 2

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

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

23. Role of ATP in cells

24. Role of ATP in cells