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Glycolysis: Allowed abbreviations Glucose N/A Glucose 6-phosphate G-6P Fructose 6-phosphate F-6P Fructose 1,6-bisphosphate F-1,6BP Dihydroxyacetone phosphate DHAP Glyceraldehyde 3-phosphate G-3P 1,3-Bisphosphoglycerate 1,3-BPG 3-phosphoglycerate 3-PG 2-phosphoglycerate 2-PG Phosphoenolpyruvate PEP Pyruvate N/A Fates of Other Sugars GLUCONEOGENESIS Gluconeogenesis Synthesis of "new glucose" from common metabolites Humans consume 160 g of glucose per day 75% of that is in the brain Body fluids contain only 20 g of glucose Glycogen stores yield 180-200 g of glucose So the body must be able to make its own glucose Substrates for Gluconeogenesis Pyruvate, lactate, glycerol, amino acids and all TCA intermediates can be utilized Fatty acids cannot! Why? Most fatty acids yield only acetyl-CoA Acetyl-CoA (through TCA cycle) cannot provide for net synthesis of sugars Gluconeogenesis Occurs mainly in liver and kidneys Not the mere reversal of glycolysis for 2 reasons: Energetics must change to make gluconeogenesis favorable (delta G of glycolysis = -74 kJ/mol Reciprocal regulation must turn one on and the other off - this requires something new! Gluconeogenesis Something Borrowed, Something New Seven steps of glycolysis are retained: Steps 2 and 4-9 Three steps are replaced or bypassed: Steps 1, 3, and 10 (the regulated steps!) The new reactions provide for a spontaneous pathway (G negative in the direction of sugar synthesis), and they provide new mechanisms of regulation Make sure you know the THREE BYPASS STEPS of Gluconeogenesis 1st bypass reaction: Pyruvate → PEP Pyruvate is converted back to PEP in two steps. Not shown here is the transport process: since oxaloacetate is usually found in the mitochondrial matrix, it must be transported out into the cytosol. However, there is no transporter for oxaloacetate. 1st bypass reaction: Pyruvate → PEP Therefore, oxaloacetate is reduced to malate first using malate dehydrogenase. Malate is transported out into the cytosol and then reoxidized back to oxaloacetate 2nd bypass reaction: Fructose 1,6-Bisphosphate → Fructose 6-phosphate Technically the reverse of the glycolytic reaction, but it is mediated by a different enzyme. 2nd bypass reaction: Glucose 6-Phosphate → Glucose Mediated by a different enzyme. Cori cycle Pentose Phosphate Pathway