LOs - Principles of Carbohydrate Metabolism 1. Describe...

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Principles of Carbohydrate Metabolism 1. Describe enzymatic digestion of starch and glycogen, and dietary disaccharides specificying glycosidic bond targets/products. a. Carb digestion starts in saliva w amylase stomach pH stops amylases in SI, disaccharides/ polymers broken down into monosaccharides into circulation b. Lactose glucose + galactose via lactase c. Sucrose glucose + fructose 2. Enzymes in glycogen synthesis a. Starts w glycogenin = primer to start new chains, and enzyme that catalyzes their assembly b. Hexokinase/glucokinase (Glucose G6P) c. Phosphoglucomutase (G6P G1P) i. Freely reversible enzyme d. UDP-Glu Pyrophosphorylase – priming step i. G1P + UTP = UDP-glucose (universal donor of glucose in mammalian cells) e. Glycogen synthase – regulated! i. UDP-Glu + glycogen (n residues) Glycogen (n+1 residues) + UDP f. Branching enzyme i. Take off 7 glucoses by breaking alpha-1,4 glycosidic bond, transfer to another position to make alpha-1,6 glycosidic bond = branch point. 3. Enzymes in glycogen degradation a. Glycogen phosphorylase – regulated! i. Removes 1 glucose from non-reducing end ii. Uses Pi (phosphorylsis) to give G1P (not free glucose) b. Debranching enzyme—bifunctional enzyme i. Take off 3, transfer to another end (breaking 1 alpha-1,4 and making another) ii. Cleaves alpha 1-6 bond = get free glucose 4. Compare cell-type expression of glucokinase and hexokinase, their regulation by insulin, by end- product inhibition, and their Km for glucose. Characteristic Glucokinase Hexokinase Cell-type expression Only in liver cells Constitutively in all cells Regulation by insulin Induced by insulin (tells cells --
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a lot of glucose available) Product inhibition None Inhibited by G6P (product) Km (glucose) 10 -2 M 10 -4 M 5. Roles of glucokinase, glut2, G6Phosphatase in glucose uptake and release by liver a. GLUT2: constitutively in the liver membrane; how glucose taken into liver from bloodsream b. G6Phosphatase: Cleaves off Pi i. Transporters: G6P (T1), Pi (T2), glucose (T3) allows free glucose to be released by liver 6. Role of 2 nd messengers and protein phosphorylation/dephosphorylation in regulation of glycogen metabolism a. Make glycogen when glucose high, insulin high, glucagon low b. Break down glycogen when glucose low, insulin low, glucagon high i. Glucagon binds to receptor cAMP made binds to regulatory subunit of PKA activates catalytic subunit ii. W/o Pi favors inactive conformation, w Pi favors active conformation 7. Regulation of glycogen phosphorylase and glycogen synthase by glucagon, including role of PKA and phosphatase inhibitors a. PKA i. PKA Pi’s phosphorylase kinase phosphorylase kinase Pi’s glycogen phosphorylase glycogen breakdown ii. PKA Pi’s glycogen synthase, which is inactivated makes sure proves working to facilitate breakdown b. Phosphatase inhibitor i. PKA Pi’s phosphatase inhibitor 1a to make it active it binds to phosphoprotein
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This note was uploaded on 09/14/2011 for the course PHARM ERM taught by Professor Staff during the Spring '11 term at UCSD.

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LOs - Principles of Carbohydrate Metabolism 1. Describe...

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