1. Regulation of Metabolism Lecture 28-Kumar
How does the body know when to increase metabolism? Slow metabolism?
What might be some indicators of energy status within the cell?
Requires communication
Works through allosteric regulation of enzyme activity

2. Mechanisms of Cellular Communication
Figure Overview

3. What Hormones Regulate Metabolism?
Insulin
Glucagon
Thyroid hormone
Cortisol
Epinephrine
Most regulation occurs in order to maintain stable blood glucose concentrations for supplying fuel to the brain!

4. Protein or peptide hormone
Almost always proteins called kinases
Activation/inactivation of an enzyme; opening/closing a membrane channel; activating a transcription factor
Figure 6-3

5. one islet of Langerhans
Pancreas
one islet of Langerhans
Digestive enzymes
and NaHCO3
hormones

7. Anabolic hormone fatty acid & amino acid uptake  Glycolysis
 Glycogen synth.
 Lipogenesis
 Protein synth.
Plasma fatty acids, ketoacids & amino acids

8. Catabolic hormone

10. Mechanism of Insulin Action

11. Principal Actions of Insulin
Rapid (seconds)
Increased transport of glucose, amino acids, and K+ into insulin-sensitive cells
2. Intermediate (minutes)
Stimulation of protein synthesis Inhibition of protein degradation Activation of glycogen synthetase and glycolytic enzymes Inhibition of phosphorylase and gluconeogenic enzymes
3. Delayed (hours)
Increase in mRNAs for lipogenic and other enzymes, c-fos

12. Major Effects of Insulin
Skeletal muscle takes up glucose from blood
Liver takes up glucose, increases glycogen production
Liver increases fatty acid synthesis when its glycogen stores are full
Adipose takes up blood glucose and fatty acid breakdown is inhibited
Overall insulin has a fat sparing action. It works to store excess energy

13. Mechanism of action for glucagon
Glucagon from a cells of pancreas
Figure Overview

15. Effects of Glucagon and Insulin on Glucose Metabolism

16. Bifunctional PFK2/FBPase2 assembles into a homodimer.
The allosteric regulator fructose-2,6-bisphosphate is synthesized & degraded by a bi-functional enzyme that includes 2 catalytic domains:
Phosphofructokinase-2 (PFK2) domain catalyzes:
Fructose-6-phosphate + ATP  fructose-2,6-bisphosphate + ADP
Fructose-Biophosphatase-2 (FBPase2) domain catalyzes:
Fructose-2,6-bisphosphate + H2O  fructose-6-phosphate + Pi
Bifunctional PFK2/FBPase2 assembles into a homodimer.

17. Fructose-2,6-bisphosphate

18. FIGURE 15-16c Role of fructose 2,6-bisphosphate in regulation of glycolysis and gluconeogenesis. Fructose 2,6-bisphosphate (F26BP) has opposite effects on the enzymatic activities of phosphofructokinase-1 (PFK-1, a glycolytic enzyme) and fructose 1,6-bisphosphatase (FBPase-1, a gluconeogenic enzyme). (c) Summary of regulation by F26BP.

20. Cortisol: slow catabolic effects; response to long-term stress
increases protein breakdown in muscles and fat breakdown in adipose tissue, elevating amino acids and fatty acids in blood.
increases glycogenolysis and gluconeogenesis in liver; elevates blood glucose
synergistic effect for actions of glucagon and epinephrine in elevating blood glucose
anti-inflammatory: inhibits cytokine activation of immune system
Long-term excessive cortisol levels can cause severe muscle breakdown, lipolysis, and hyperglycemia. Hypersecretion may be from a tumor (Cushing's disease) or excess ACTH.

22. Test Your Knowledge
The major hormones that promote glucose release into the blood are:
The major hormones that promote storage of glucose are:
A hepatic cell has receptors for epinephrine, glucagon, and insulin. These hormones may or may not act in concert to produce a desired effect. How does the hepatocyte know what to do?
What are the major second messenger systems used by the hormones that regulate blood glucose? What is the end result of activation of these second messenger systems?