Gluconeogensis - Lecture 38: Gluconeogenesis Cori and...

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Lecture 38: Gluconeogenesis Cori and Alanine Cycle 1. depend on Gluconeogenesis in liver followed by delivery of glucose to a peripheral tissue 2. Both cycles provide mechanism for continuously suppying tissues that require glucose as their primary energy source 3. The cycles are only functional between liver and tissue that do not completely oxidize glucose to CO2 and H2O 4. Differences a. The type of recycled 3-carbon intermediate is the major difference i. Cori – lactate ii. Alanine - alanine b. NADH generated differs i. Cori – used for lactate production ii. Alanin – used by malate-asp shuttle for oxidative phosphorylation 1. pyruvate is converted to alanine by transaminiaiton with glutamate 5. Pathway of Gluconeogenesis from lactate
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Pathway of Gluconeogenesis from lactate
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1. Many enzymes of glycolysis are common to the gluconeogenic pathway. Additional reactions have to be involved because glycolysis produces 2 ATP and gluconeogenesis requires 6 ATP per molecule of glucose. 2. Irreversible steps of glycolysis are replaced by other irreversible steps for the gluconeogenic pathway. 3. Initial step is conversion of lactate to pyruvate by lactate dehydrogenase. The NADH generated in this step is needed for a subsequent step in the pathway. 4. Pyruvate cannot be converted to phospho enol pyruvate (PEP) by pyruvate kinase because the reaction is irreversible. 5. Pyruvate is converted into the high-energy phosphate compound PEP by coupling of two reactions requiring high-energy phosphate compounds (an ATP and a GTP). 6. Pathway a. Pyruvate carboxylase catalyzes the first reaction b. PEP carboxykinase catalyzes the second reaction i. GTP required (ATP equivalent through the action of nucleoside diphosphate kinase (GDP + ATP GTP + ADP) ii. CO2 generated and HCO 3 - required by pyruvate carboxylase are linked by the reaction catalyzed by carbonic anhydrase (CO2 + H2O -> H2CO3 + H+ + HCO3–) 7. Thus the conversion of pyruvate into PEP during gluconeogenesis costs the cell 2 molecules of ATP a. In contrast to the conversion of PEP to pyruvate during glycolysis which yields the cell 1 molec ATP 8. pyruvate carboxylase : mitochondrial 9. PEP carboxykinase : both cytosolic and mitosolic compartments 10. 2 ways to go from OAA to glucose a. Mitochondrial PEP carboxykinase OAA is converted to PEP in mitosol, then traverses the mitochondrial inner membrane b. OAA converted into aspartate, exits into the cytosol by way of glutamate-aspartate antiport i. Aspartate transaminates with α -ketoglutarate in the cytosol to produce OAA, which is used by cytosolic PEP carboxykinase for the synthesis of PEP 1. OAA can’t just traverse the mitochondrial inner membrane Gluconeogenesis uses many glycolytic enzymes but in the reverse direction 1. enzymes operate in reverse to convert PEP to fructose 1,6-bisphosphate during gluconeogenesis 2. NADH generated by lactate dehydrogenase is used by glyceraldehyde 3-phosphate , establishing an equal balance of generation and utilization of reducing agents
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Gluconeogensis - Lecture 38: Gluconeogenesis Cori and...

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