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Gluconeogenesis Gluconeogenesis Glucogenic amino acids Lactate, pyruvate Propionate (ruminants) Glucose Glycerols (from triglycerides) Krebs cycle intermediates Roles of Gluconeogenesis Provides glucose for the brain Recycles lactate after exercise Lactose synthesis in ruminants Carbohydrate polymers in plants and bacteria From CO2, acetate, fats, etc… Review of Glycolysis Glucose ²G ATP –33 kJ/mol ADP Glu-6-P Fru-6-P ATP –22 kJ/mol ADP Fru-1,6-bisP DHAP Glyceraldehyde-3-P Review of Glycolysis Glyceraldehyde-3-P 1,3-bis PGA ²G ADP +1 kJ/mol ATP 3-PGA 2-PGA PEP Pyruvate ADP –17 kJ/mol ATP Bypasses of “Irreversible” Glycolysis Steps ATP Glucose ADP Glucose-6-P Glucose-6-phosphatase Pi Bypasses of “Irreversible” Glycolysis Steps ATP Fructose-6-P ADP Fructose-1,6-bisP FBPase-1 Pi Bypasses of “Irreversible” Glycolysis Steps Cori Cycle: Lactate Salvage GlucoseAlanine Cycle Gluconeogenesis from Stored Fats In plants Triacylglycerols Glycerol Fatty acids -oxidation Acetyl-CoA Glyoxylate cycle Oxaloacetate PEP carboxykinase PEP Gluconeogenesis Glucose Gluconeogenesis from Stored Fats In Triacylglycerols animals CH2OH Fatty acids Glycerol CHOH Glycerol kinase CH2OH Glycerol-P Glycerol-P DH Dihydroxyacetone-P Triose-P isomerase Glyceraldehye-3-P Gluconeogenesis Glucose Gluconeogenesis from Propionate In Cellulose, etc... Protozoa, bacteria ferment ruminants Propionate Propionyl-CoA carboxylase Methylmalonyl-CoA B12 Succinyl-CoA Krebs cycle Oxaloacetate PEP Glucose Galactose Lactose Fate of Pyruvate: Regulation Gluconeogenesis and Glycolysis Reciprocal ATP regulation Fru-6-P PFK-1 ADP Pi FBPase-1 Fru-1,6-bisP Net reaction: ATP ADP + Pi (a futile cycle) Reciprocal Regulation of PFK-1 and FBPase-1 Both enzymes allosterically regulated by Fru-2,6-bisP P O CH2 O CH2O P P O CH2 O CH2OH HO OH HO O P OH Fru-1,6-bisP (substrate/product) OH Fru-2,6-bisP (allosteric regulator) Regulation by Fru-2,6-bisP Regulation by Fru-2,6-bisP Fru-2,6-bisP as Regulator Fru-2,6-bisP ATP Fru-6-P ADP Fru-1,6-bisP Pi (in mammals) Glycolysis Gluconeogenesis What Regulates [Fru-2,6-bisP]? Indirectly ATP regulated by the hormone glucagon Fru-6-P PFK-2 ADP Glucagon: (in liver) Pi FBPase-2 Fru-2,6-bisP } FBPase-2 PFK-2 [Fru-2,6-bisP] PFK-2 and FBPase-1: Same Protein!
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