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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. Mechanisms of Cellular Communication.
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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
Mechanisms of Cellular Communication Figure 6-1 - Overview
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!
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
Steroid Hormones (examples: cortisol, testosterone, estrogen Figure 6-4 (2 of 3)
Protein/peptide hormones (examples: epinephrine, insulin, glucagon, oxytocin) Figure 6-4 (3 of 3)
Amplification What are some advantages to having an amplified signal? What might be some disadvantages? Figure 6-7
How is the signal from the hormone (signal molecule) binding to the receptor transmitted into the interior of the cell? Figure 6-8
Insulin works through a tyrosine kinase (TK) receptor mechanism Insulin from b cells of the pancreas Figure 6-10
Insulin regulation of glucose entry in skeletal muscle *Overall insulin promotes storage of glucose as a fuel and a reduction of blood glucose when elevated Figure taken from: http://www.smbs.buffalo.edu/bch/Courses/bch404/GW_Nature_InsulinSig.pdf#search=%22GLUT4%20vesicles%20micrograph%22
Insulin regulation of glucose metabolism in the liver Figure taken from: http://www.smbs.buffalo.edu/bch/Courses/bch404/GW_Nature_InsulinSig.pdf#search=%22GLUT4%20vesicles%20micrograph%22
Figure taken from: http://www.smbs.buffalo.edu/bch/Courses/bch404/GW_Nature_InsulinSig.pdf#search=%22GLUT4%20vesicles%20micrograph%22
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
Mechanism of action for glucagon Glucagon from a cells of pancreas Figure 6-11 - Overview
Major effects of glucagon: • Stimulates breakdown of glycogen stored in the liver • Activates hepatic gluconeogenesis (using amino acids and other non-carbohydrate precursors) Overall the effects of glucagon are to increase blood glucose when it is low Figure from: http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/glucagon.html
Glucogenic amino acids Lactate from muscle (Cori Cycle) Figure taken from: http://web.indstate.edu/thcme/mwking/gluconeogenesis.html
Figure taken from: http://web.indstate.edu/thcme/mwking/gluconeogenesis.html
Thyroid releasing hormone/Thyroid stimulating hormone/Thyroid hormone Hypothalamus Anterior pituitary Thyroid gland Figure 6-12 - Overview
Increased metabolic rate and heat production • Increased fat mobilization • Increased carbohydrate metabolism Figure taken from: http://www.nature.com/ncpendmet/journal/v1/n1/fig_tab/ncpendmet0020_F1.html
Epinephrine works on cells via Ca2+ as a second messenger • Increases glycogenolysis and gluconeogenesis • Increases release of glucagon and cortisol Figure 6-15
Epinephrine can also work via the cAMP signal transduction pathway Phosphorylation of glycogen phosphorylase; increases breakdown of glycogen in liver
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?
