02.07 - Lee - Gluconeogenesis

02.07 - Lee - Gluconeogenesis - Gluconeogenesis Uses...

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Gluconeogenesis: Uses reversible portion of the glycolytic pathway plus four new enzyme reactions. Pathways of glycolysis and gluconeogenesis are co- ordinately regulated by both allosteric and hormonal mechanisms. Sources of precursors for gluconeogenesis - connection with the Krebs cycle. 2008 Gluconeogenesis. Utilizes the reversible steps of glycolysis. Involves the synthesis of glucose from pyruvate (or other intermediates that can be converted to pyruvate - e.g. lactate, alanine). Is carried out in the liver, and to a lesser extent, in the kidney. 2008 Gluokinase Pyruvate kinase Phosphofructo- kinase Phosphoglucose isomerase Aldolase Triosephosphate isomerase Glyceraldehyde 3-phosphate dehydrogenase Phosphoglycerate kinase Phosphoglycerate mutase Enolase Overview of Glycolysis
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Glucokinase PFK Pyruvate kinase Energy Profiles For Glycolytic Pathway. There are three points at which there are large energy drops (negative Δ Gs). These are the reactions which are essentially unidirectional. Δ G for the formation of pyruvate from glucose is about -20 kcal/mol. This energy comes from the three steps catalyzed by hexokinase, PFK, and pyruvate kinase). The irreversible steps in glycolysis that need to be bypassed PEP F1,6-bisP F6-P G6-P Glucose Pyruvate Δ G GLUCOSE Fructose 6P Fructose 1,6P Triose P Pyruvate PEP Glucose 6P Oxaloacetate Glucose 6 phosphatase Fructose 1, 6 bisphosphatase Glucokinase Phosphofructokinase Pyruvate carboxylase Pyruvate kinase Phosphoenolpyruvate Carboxykinase (PEPCK) Bypass of the three irreversible steps of glycolysis. 1 2 3 Bypass 1. Requires two step conversion of pyruvate to PEP via oxaloacetate by pyruvate carboxylase and PEPCK. Bypass 2. Requires F1,6 bisphosphatase. Bypass 3. Requires glucose 6-phosphatase At the same time, the three glycolytic enzymes must be inhibited. The First Bypass. Pyruvate is converted to Oxaloacetate and then to PEP COO - C=O CH 3 COO - C=O CH 2 COO - CO 2 ATP Pyruvate Oxaloacetate The pyruvate to PEP reaction is energetically unfavorable. Resynthesis of PEP is therefore performed in two steps, each of which requires input of an ATP equivalent. One ATP is used by pyruvate carboxylase, and one GTP by PEP carboxykinase. Hydrolysis of GTP and decarboxylation are used to drive the formation of PEP from oxaloacetate. pyruvate carboxylase COO - C-O-PO 3 2- CH 2 GTP CO 2 Phosphoenolpyruvate PEP carboxykinase (PEPCK)
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Synthesis of PEP from pyruvate via oxaloacetate.
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This note was uploaded on 04/18/2008 for the course BIOC 1010 taught by Professor Zhang during the Fall '07 term at New York Medical College.

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02.07 - Lee - Gluconeogenesis - Gluconeogenesis Uses...

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