PowerPoint PresentationSlide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Slide 39Slide 40Slide 41Slide 42Slide 43Glucose-6-P is common to several metabolic pathwaysSlide 45Slide 46Slide 47Slide 48Slide 49Slide 50Slide 51Slide 52Slide 53Slide 54Slide 55Slide 56Balancing the needs for ATP, NADPH, and ribose 5-phosphateSlide 58Slide 59Slide 60Slide 61Slide 62Learning GoalsSlide 64Slide 65Slide 66Gluconeogenesis is an important metabolic pathway during times of fastingGluconeogenesis is an important metabolic pathway during times of fastingLecture 16- Chapters 17 + 26Gluconeogenesis and the Pentose Phosphate PathwayLecture 16- Chapters 17 + 26Gluconeogenesis and the Pentose Phosphate PathwayOutlineOutline•Glucose can be synthesized from noncarbohydrate precursors•Gluconeogenesis and glycolysis are reciprocally regulated•The Cori cycle•Glucose can be synthesized from noncarbohydrate precursors•Gluconeogenesis and glycolysis are reciprocally regulated•The Cori cycle- Purpose of the Pentose Phosphate Pathway (PPP)- Oxidative phase- Nonoxidative phase- Balancing the cellular needs for ATP, NADPH and ribose-5-P- Purpose of the Pentose Phosphate Pathway (PPP)- Oxidative phase- Nonoxidative phase- Balancing the cellular needs for ATP, NADPH and ribose-5-PTo the liverTo the liverhttp://dtc.ucsf.edu/types-of-diabetes/type1/understanding-type-1-diabetes/how-the-body-processes-sugar/the-liver-blood-sugar/http://dtc.ucsf.edu/types-of-diabetes/type1/understanding-type-1-diabetes/how-the-body-processes-sugar/the-liver-blood-sugar/LactateLactateglycerolglycerolAmino acidsAmino acidsLactateLactateConverted to glucoseGluconeogenesisGlycogenolysisThe Liver Regulates Blood Sugar LevelsThe Liver Regulates Blood Sugar LevelsGluconeogenesis-Glucose is synthesized- ATP is consumed- NADH is oxidized to NAD+Gluconeogenesis-Glucose is synthesized- ATP is consumed- NADH is oxidized to NAD+ In some ways, Gluconeogenesis is the reverse of Glycolysis In some ways, Gluconeogenesis is the reverse of GlycolysisGlycolysis-Glucose is catabolized- ATP is produced -NAD+ is reduced to NADH Glycolysis-Glucose is catabolized- ATP is produced -NAD+ is reduced to NADHHowever, the reactions in the Gluconeogenesis pathway CANNOT be the exact reverse of the reactions in the Glycolysis pathway.However, the reactions in the Gluconeogenesis pathway CANNOT be the exact reverse of the reactions in the Glycolysis pathway.WHY ?WHY ?Gluconeogenesis is not exactly the reverse of GlycolysisGluconeogenesis is not exactly the reverse of Glycolysis2∆G°’ = -84 kJ mol-1∆G°’ = -84 kJ mol-1∆G°’ = -38 kJ mol-1∆G°’ = -38 kJ mol-1+ 2 ATP+ 2 ATP- 6 ATP equivalent- 6 ATP equivalentHexokinaseHexokinasePhosphofructokinase(PFK)Phosphofructokinase(PFK)Pyruvate KinasePyruvate KinaseGlucose-6-PhosphataseGlucose-6-PhosphataseFructose-1,6-bisphosphatase(F-1,6-BPase)Fructose-1,6-bisphosphatase(F-1,6-BPase)Pyruvate Carboxylase&PEP CarboxykinasePyruvate Carboxylase&PEP Carboxykinase∆G=-33 kJ mol-1∆G=-22 kJ mol-1∆G=-17 kJ mol-1Glycolysis -Reaction 10:Glycolysis -Reaction 10: ΔG°′ = -31.7 kJ/mol after removing the energy used to phosphorylate ADP ΔG°′ = -31.7 kJ/mol after removing the energy used to phosphorylate ADPPyruvate kinasePyruvate kinase7Gluconeogenesis -Reactions 1 & 2:Gluconeogenesis -Reactions 1 & 2:Pyruvate carboxylasePyruvate carboxylasePEP CarboxykinasePEP CarboxykinaseATPCO2GTPADPADPCO2Pyruvate is Converted to Oxaloacetate in MitochondriaPyruvate is Converted to Oxaloacetate in MitochondriaCitric acid cycleInMitochondriaInMitochondriaAcetyl CoAAcetyl CoACarboxybiotinCarboxybiotinPyruvate carboxylase requires the vitamin biotin (vit B7) as a coenzyme (proesthetic group).Pyruvate carboxylase requires the vitamin biotin (vit B7) as a coenzyme (proesthetic group).CO2CO2Citric acid cycleCitric acid cycleInMitochondriaInMitochondriaCarboxylation of Pyruvate(Pyruvate Carboxylate)Carboxylation of Pyruvate(Pyruvate Carboxylate)∆G°’ for the last step is -20 kJ mol-1∆G°’ for the last step is -20 kJ mol-1carboxyphosphatecarboxyphosphateCarboxylated biotinCarboxylated biotinOxaloacetate must move out to the cytoplasm to be converted to PEPOxaloacetate must move out to the cytoplasm to be converted to PEPmitochondriamitochondriamitochondriamitochondriaOxalacetate can then be converted to PhosphophenolpyruvateOxalacetate can then be converted to Phosphophenolpyruvatekinase(PEP)(GAP)Need two molecules of pyruvate to generate one glucoseNeed two molecules of pyruvate to generate one glucose Pyruvate PEP F1,6PaldolaseGluconeogenic-specific enzymesGluconeogenic-specific enzymesGluconeogenesis is not merely (exactly) the reverse of GlycolysisGluconeogenesis is not merely (exactly) the reverse of Glycolysis2∆G°’ = -84 kJ mol-1∆G°’ = -84 kJ mol-1∆G°’ = -38 kJ mol-1∆G°’ = -38 kJ mol-1+ 2 ATP+ 2 ATP- 6 ATP- 6 ATPHexokinaseHexokinasePhosphofructokinase(PFK)Phosphofructokinase(PFK)Pyruvate KinasePyruvate KinaseGlucose-6-PhosphataseGlucose-6-PhosphataseFructose-1,6-bisphosphatase(F-1,6-Bpase)Fructose-1,6-bisphosphatase(F-1,6-Bpase)Pyruvate Carboxylase&PEP CarboxykinasePyruvate Carboxylase&PEP Carboxykinase∆G=-33 kJ mol-1∆G=-22 kJ mol-1∆G=-17 kJ mol-1The conversion of fructose 1,6-bisphosphate into fructose 6-phosphateThe conversion of fructose 1,6-bisphosphate into fructose 6-phosphateGluconeogenesis is not merely (exactly) the reverse of GlycolysisGluconeogenesis is not merely (exactly) the reverse of Glycolysis2∆G°’ = -84 kJ mol-1∆G°’ = -84 kJ mol-1∆G°’ = -38 kJ mol-1∆G°’ = -38 kJ mol-1+ 2 ATP+ 2 ATP- 6 ATP- 6 ATPHexokinaseHexokinasePhosphofructokinase(PFK)Phosphofructokinase(PFK)Pyruvate KinasePyruvate KinaseGlucose-6-PhosphataseGlucose-6-PhosphataseFructose-1,6-bisphosphatase(F-1,6-Bpase)Fructose-1,6-bisphosphatase(F-1,6-Bpase)Pyruvate Carboxylase&PEP CarboxykinasePyruvate Carboxylase&PEP Carboxykinase∆G=-33 kJ mol-1∆G=-22 kJ mol-1∆G=-17 kJ mol-1∆G = -25 kJ/mol∆G = -25 kJ/mol∆G°’ = -16 kJ/mol∆G°’ = -16 kJ/mol∆G°’ = -13 kJ/mol∆G°’ = -13 kJ/molNeed two molecules of pyruvate to generate one glucoseNeed two molecules of pyruvate to generate one glucoseGluconeogenic-specific
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