regulation of metabolism lecture 28-kumar how does the body know when to increase metabolism? slow...
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Regulation of MetabolismLecture 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
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Figure 6-1 - Overview
Mechanisms of Cellular Communication
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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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Figure 6-3
Protein or peptide hormone
Almost always proteins called kinases
Activation/inactivation of an enzyme; opening/closing a membrane channel; activating a transcription factor
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hormones
Digestive enzymes and NaHCO3
one islet of Langerhans
Pancreas
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Plasma fatty acids, ketoacids & amino acids
fatty acid & amino acid uptake
Anabolic hormone
Glycolysis Glycogen synth. Lipogenesis Protein synth.
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Catabolic hormone
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Mechanism of Insulin Action
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Principal Actions of Insulin
1. Rapid (seconds) Increased transport of glucose, amino acids, and K+
into insulin-sensitive cells2. 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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Figure 6-11 - Overview
Mechanism of action for glucagonGlucagon from cells of pancreas
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Effects of Glucagon and Insulin on Glucose Metabolism
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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.
PFK2/FBPase2 homodimer PDB 2BIF
PFK-2 domain
FBPase-2 domain
with bound fructose-6-P in active site
The allosteric regulator fructose-2,6-bisphosphate is synthesized & degraded by a bi-functional enzyme that includes 2 catalytic domains:
PFK-2
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Fructose-2,6-bisphosphate
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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?