Regulation of Metabolism

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Regulation of Metabolism

• 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
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Mechanisms of Cellular Communication
Figure 6-1 - Overview
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• 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!
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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
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Pancreas
one islet of Langerhans
Digestive enzymes and NaHCO3
hormones
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Mechanism of Insulin Action
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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 enzymesInhibition of phosphorylase and gluconeogenic enzymes 3. Delayed (hours) Increase in mRNAs for lipogenic and other enzymes, c-fos

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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

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Mechanism of action for glucagon
Glucagon from a cells of pancreas
Figure 6-11 - Overview
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Effects of Glucagon and Insulin on Glucose
Metabolism
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PFK-2
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-bisphosp
  hate ADP
• Fructose-Biophosphatase-2 (FBPase2) domain
  catalyzes
• Fructose-2,6-bisphosphate H2O ?
  fructose-6-phosphate Pi
• Bifunctional PFK2/FBPase2 assembles into a
  homodimer.

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Fructose-2,6-bisphosphate
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cAMP as a Regulator of Glycogen Metabolism
Pkinase
Protein Kinase targets of cAPK
cAMP Protein kinase (cAPK)
Adenyl cyclase
Glucagon Epinephrine
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Insulin
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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.
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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?