1. LEHNINGER PRINCIPLES OF BIOCHEMISTRY
David L. Nelson and Michael M. Cox
LEHNINGER
PRINCIPLES OF BIOCHEMISTRY
Sixth Edition
CHAPTER 15
Principles of Metabolic Regulation
© 2013 W. H. Freeman and Company

2. Factors affecting the activity of enzymes

3. Regulation by reversible phosphorylation

4. A typical ATP-utilizing enzyme has a Km for ATP of about 5 mM The concentration of ATP in animal tissues is about 5 mM

5. Control of glycogen synthesis from blood glucose

7. Hexokinase I of muscle has a low Km for glucose Hexokinase IV of liver has a high Km for glucose

8. Regulation of phosphofructokinase-1 (PFK-1)

9. Reciprocal Regulation of PFK-1 and FBPase-1
Activated by
Fructose 2,6-bisphosphate
Inhibited by
Fructose 2,6-bisphosphate
Glucagon, a pancreatic hormone, signals low blood sugar and
lowers the level of fructose 2,6-bisphosphate in the liver.
This stimulates gluconeogenesis and the production of glucose.

10. Fructose 2,6-bisphosphate is synthesized by the enzyme phosphofructokinase-2 (PFK-2) and broken down by fructose 2,6 bisphosphatase (FBPase-2)

11. Phosphofructokinase-2 (PFK-2) and fructose 2,6 bisphosphatase (FBPase-2) are on the same polypeptide chain and regulated by glucagon

12. Regulation of Pyruvate Kinase
Pyruvate kinase is inhibited by:
ATP
acetyl-CoA
long-chain fatty acids
High concentrations of ATP signals that glycolysis is not
needed for further production of ATP.
Acetyl-CoA and fatty acids are fuels for the citric acid
cycle. When there is plenty of fuel for the citric
acid cycle glycolysis is not needed to provide
acetyl-CoA for the citric acid cycle.

13. Regulation of Pyruvate Kinase

14. Glycogen Metabolism

15. Glycogen phosphorylase degrades glycogen

17. Hydrolysis of glucose 6-phosphate occurs in the ER

18. UDP-glucose, synthesized from glucose 1-phosphate, is the glucose donor for glycogen synthesis

19. Branch synthesis in glycogen
Why is glycogen branched?
Make the glycogen molecule more soluble.
Increase the number of reducing ends, the ends where glycogen synthase adds more glucose residues and where glycogen phosphorylase removes glucose residues.

20. Glycogenin primes the initial sugar residues in glycogen
The initial glucose monomer (from UDP-glucose) is covalently attached to a tyrosine residue on glycogenin

22. Regulation of glycogen phosphorylase
Activated by glucagon

23. Glucose binds to an allosteric site on glycogen phosphorylase a and induces a conformational change that exposes the phosphorylated serines to phosphorylase a phosphatase.
The result is a decrease in glycogen breakdown in response to high blood glucose levels.

24. Regulation of glycogen synthase
Insulin promotes activation of glycogen synthase and blocks inactivation of glycogen synthase
Glucagon blocks activation of glycogen synthase