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GLUCONEOGENESIS

GLUCONEOGENESIS. Most organisms have the ability to synthesise glucose from common metabolites The body carries only slightly more than one day’s supply of glucose so if glucose is not taken in the diet, the body must produce glucose from non carbohydrate precursors.

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GLUCONEOGENESIS

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  1. GLUCONEOGENESIS

  2. Most organisms have the ability to synthesise glucose from common metabolites • The body carries only slightly more than one day’s supply of glucose so if glucose is not taken in the diet, the body must produce glucose from non carbohydrate precursors. • Also under anaerobic conditions, lactate that is produced can be reconverted to glucose • Lactate passes into the blood stream to the liver and is converted to pyruvate by lactate dehydrogenase. • In the liver 80% of lactate is changed to glucose while the remaining 20% is oxidised by the TCA cycle.

  3. Although the brain and muscle consumes the most glucose, it is in the liver (90%) and kidneys (10%) that most gluconeogenesis occurs. • Glucose produced by gluconeogenesis in the liver and kidney is released into the blood and is subsequently absorbed by brain, heart, muscle, and red blood cells to meet their metabolic needs. • Lactate formed in the muscle can be recycled to glucose in the liver via the Cori Cycle www.rpi.edu/.../MBWeb/mb1/part2/gluconeo.htm

  4. -3.4 kcal/mol -3.4kcal/mol -4kcal/mol

  5. Pyruvate to oxaloacetate (1st bypass) • G = - 0.5 kcal/mol Enzyme: Pyruvate carboxylase • Pyruvate carboxylase is an allosteric enzyme • Acetyl Co A is a positive modulator • Uses ATP • Oxaloacetate to malate (in the mitochondria) G = - 6.7 kcal/mol • Enzyme: malate dehydrogenase • Found in the mitochondria • NADH is converted to NAD+ • Malate that is formed leaves the mitochondria via the dicarboxylate transport system that is found in the inner mitochondrial membrane

  6. GLUCONEOGENESIS + NAD+ Pyruvate Oxaloacetate Malate Malate dehydrogenase G =+6.7 kcal/mol cytoplasm Inner mitochondrial membrane mitochondria + CO2 + ATP + NADH Oxaloacetate Malate Pyruvate Malate dehydrogenase Pyruvate carboxylase G = - 0.5 kcal/mol G = - 6.7 kcal/mol Dicarboxylate transport system Overall reaction: Pyruvate + CO2 + ATP Oxaloacetate + ADP + Pi

  7. Oxaloacetate to phosphoenol pyruvate G = +1.0 kcal/mol • Enzyme: PEP carboxykinase • Uses GTP • From 4 carbon molecule to a 3 carbon molecule • Note up to now, 2 nucleoside triphosphates have been used: ATP and GTP • Overall reaction from pyruvate to PEP : G = +0.5 kcal/mol

  8. PEP to Fructose 1,6 bisphosphate • Involves 6 enzymes that are similar to glycolysis and is the reversal of glycolysis • Note that when 3 PG is changed to 1,3bPG, 1 ATP is used • Fructose 1,6 bisP to fructose 6-P • (2nd bypass) • G = -3.4 kcal/mol • Catalysed by fructose diphosphatase • Allosteric enzyme • This enzyme is stimulated when the energy level in the cell is high and is inhibited by high levels of AMP

  9. Glucose 6-P to glucose • (3rd bypass) • G = -3.3 kcal/mol • Catalysed by glucose 6-phosphatase • This enzyme is not found in the brain and muscle tissues • Allosteric enzyme: activity is stimulated by citrate and 3-phosphoglycerate but inhibited by AMP

  10. During gluconeogenesis, 1 molecule of glucose 6-phosphate is formed from pyruvate. • Utilises 4 ATP and 2 GTP (require 2 pyruvate molecules) • 2 Pyruvate + 4 ATP + 2GTP + 2 NADH + 2H+ +6H2O • Glucose 6-phosphate + 4 ADP + 2GDP + 2 NAD+ + 5Pi

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