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Regulation of Metabolism • How does the body know when to increase metabolism? Slow metabolism? Requires communication • What might be some indicators of energy status within the cell? Works through allosteric regulation of enzyme activity Mechanisms of Cellular Communication Figure 6-1 - Overview Figure 6-2b Figure 6-2c Figure 6-2a 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) Figure 6-5 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 Table 6-1 Table 6-2 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.pd f#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 noncarbohydrate precursors) Overall the effects of glucagon are to increase blood glucose when it is low Figure from: http://www.vivo.colostate.edu/hbooks/pathphys/endo crine/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/gluco neogenesis.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? Figure 6-14 Figure 6-16 Figure 6-17 Table 6-3 Table 6-5