HNF 461 1st Edition Lecture 7 Outline of Last Lecture I Gluconeogenesis a Precursors II Fatty Acid Oxidation a Pyruvate Kinase Bypass III Amino Acid Metabolism IV Cori Cycle V Alanine Cycle VI Glucocorticoids a Cortisol VII Carbohydrate Metabolism During Stress Exercise a Fight Flight Response Outline of Current Lecture I Review of Gluconeogenesis II Regulation of Gluconeogenesis III Shutting Down Pyruvate Kinase IV Initiating Conversion of Oxaloacetate from Pyruvate V Bypassing the Phosphofructokinase Reaction VI Bypassing the Glucokinase Reaction These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute VII Long Term Effects of Glucagon Current Lecture Key Enzymes in Gluconeogenesis 1 Review of Gluconeogenesis a Occurs in the liver b Low blood glucose c High glucagon low insulin levels d Fatty acids and glycerol are released from fat into the liver e Amino acids are released from muscles into the liver 2 Regulation of Gluconeogenesis a Short term regulated by glucagon insulin and substrates building blocks b Long term regulated by the amount of enzymes present Note 3 reactions in glycolysis are nonreversible so in order for gluconeogenesis to occur they must be bypassed The following in this outline discusses how this is achieved 3 Shutting Down the Pyruvate Kinase Pathway a Glucagon Inactivates Pyruvate Kinase i Glucagon cAMP Protein Kinase A Pyruvate Kinase inactivation Glycolysis inactivation b This allows for Oxaloacetate to be formed from pyruvate 4 Initiating Pyruvate to Oxaloacetate Conversion a Fatty acids oxidized in the liver produce acetyl CoA b Acetyl CoA activates Pyruvate Carboxylase i Gluconeogenesis Pyruvate Oxaloacetate ii Oxaloacetate is converted to glucose c Acetyl CoA inhibits Pyruvate Dehydrogenase Complex i Pyruvate Acetyl CoA d Glycolysis is inhibited because other enzymes have been inhibited ex pyruvate kinase 5 Bypassing Phosphofructokinase Reaction a Fructose 2 6 bisphosphate F 2 6 BisP inhibits FBP 1 gluconeogenesis and activates PFK 1 glycolysis b When glucagon is present it activates Fructose 2 6 bisphosphate F 2 6 BisP F 6 P so F 2 6 BisP level decreases c Decrease of F 2 6 BisP lifts both the inhibition of FBP 1 gluconeogenesis and the activation of PFK 1 glycolysis d AMP can also activate PFK 1 glycolysis i When AMP concentrations are low in the liver PFK 1 is not active and gluconeogenesis occurs 6 Bypassing Glucokinase Reaction a Happens in the liver b Glucokinase GK phosphorylates glucose Glucose 6 Phosphatase dephosphorylates glucose c When the Fructose 6 Phosphate Glucose ratio is high the translocation of GK to the nucleus is initiated and phosphorylation of glucose is inhibited d Glucose 6 Phosphatase converts Glucose 6 Phosphate to free glucose which can leave the liver 7 Long Term Effects of Glucagon a Increases the amount of PEP carboxykinase b Decrease the amount of key enzymes in glycolysis
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