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Unformatted text preview: Lecture 11 – Pentose Shunt/Metabolism in Well Fed State/Starvation Liver is the mastermind of metabolism of the body Regulation of metabolism by insulin and glucagon- Fluctuations in Insulin and Glucagon in response to a carboydrate rich diet. o After meals the amount of insulin raises to clear the glucose and before breakfast it is lowest Glucose goes up Insulin goes up glucagon goes down clear glucose WELL FED STATE Insulin receptor- Insulin binding activates receptor tyrosine kinase activity in the intracellular domain of the beta subunit of the insulin receptor o Tyrosine resides of the beta subunit are autophosphorylated !- This leads to many downstream signaling o It phosphorylates other proteins ( insulin receptor substrates IRS ) o IRS goes on to promote activation of other protein kinases and phophatases, leading to biologic insulin action o Glucose uptake UP o Glycogen synthesis UP o Protein synthesis UP o Fat synthesis UP o Gluconeogenesis DOWN o Glycogenolysis DOWN o Lipolysis DOWN- Daily fluctuations in metabolism o Well fed state (glucose in blood (this is 2/3 of digested glucose) enters liver glucose goes through glycolysis, fatty acid synthesis, used as fuel/ene FAs leave liver via VLDL to adipose tissue Liver metabolism (insulin present) GLUT2 (always on surface, constituitive)- Brain needs glucose so it has to make sure that there is enough glucose in the blood! Glycogen metabolism Glycolysis Fatty Acid metabolism- Glucose Transporter (Glut2) is always on surface.- Glucokinase is induced by insulin.- cAMP is absent; PKA is off.- Glycogen Synthase is on.- Phosphorylase Kinase is off.- Glycogen Phosphorylase is off.- Phosphatase Inhibitor is inactive.- Pyruvate Kinase is active.- PFK2 is active as a kinase.- PEPCK is not induced. It is induced by Glucagon.- F 1,6bis Phosphatase is induced by Glucagon.- Citric Acid Shuttle is active.- Acetyl CoA Carboxylase is active. - Pentose-P Shunt enzymes are induced by insulin. Adipocyte s (stora ge ) GLUT 4 (regulated by insulin; absence of insulin the receptors are in vesicles not on surface with insulin then it will mobilize to surface)- TGs made in liver are stored in adipocytes- Metabolism in well fed state o Insulin is bound to Insulin Receptor (activate the kinase) o Glucose Transporter is mobilized at the surface of the adipocyte (so glucose...
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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.
- Spring '11