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 35Glucose-6-P is common to several metabolic pathwaysSlide 37Slide 38Slide 39Slide 40Slide 41Slide 42Slide 43Slide 44Slide 45Slide 46Slide 47Slide 48Slide 49Slide 50Slide 51Balancing the needs for ATP, NADPH, and ribose 5-phosphateSlide 53Slide 54Slide 55Slide 56Learning GoalsLecture 16- Chapters 17 + 26Gluconeogenesis and the Pentose Phosphate Pathway•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-PLactateGlycerolAmino acidsLactateThe Liver Regulates Blood Sugar LevelsGluconeogenesis-Glucose is synthesized- ATP is consumed- NADH is oxidized to NAD+ In some ways, Gluconeogenesis is the reverse of GlycolysisGlycolysis-Glucose is catabolized- ATP is produced -NAD+ is reduced to NADH The reactions in the Gluconeogenesis pathway CANNOT be the exact reverse of the reactions in the Glycolysis pathway. WHY?Gluconeogenesis is not exactly the reverse of Glycolysis∆G°’ = -84 kJ mol-1∆G°’ = -38 kJ mol-1+ 2 ATP- 6 ATP equivalent∆G=-33 kJ mol-1∆G=-22 kJ mol-1∆G=-17 kJ mol-1Glycolysis -Reaction 10: ΔG°′ = -31.7 kJ/mol after ATP productionPyruvate kinase5Gluconeogenesis -Reactions 1 & 2:PEP CarboxykinaseATPCO2GTPADPADPCO2Pyruvate is Converted to Oxaloacetate in MitochondriaBIOTIN(Vit B7)BIOTINIn MitochondriaOxaloacetate must move out to the cytoplasm to be converted to PEPCarboxylation of Pyruvate(Pyruvate Carboxylate)∆G°’ for the last step is -20 kJ mol-1carboxyphosphatecarboxylated biotinHCO3- + ATP HOCO2-PO32- + ADPBiotin-E + HOCO2-PO32- + CO2-Biotin-E + PiCO2-Biotin-E + pyruvate Biotin-E + oxaloacetateOxalacetate can then be converted to PhosphophenolpyruvatecarboxykinaseOxaloacetate can then be converted to PhosphoenolpyruvateNeed two molecules of pyruvate to generate one glucoseGluconeogenesis is not exactly the reverse of Glycolysis∆G°’ = -84 kJ mol-1∆G°’ = -38 kJ mol-1+ 2 ATP- 6 ATP equivalent∆G=-33 kJ mol-1∆G=-22 kJ mol-1∆G=-17 kJ mol-1The conversion of fructose 1,6-bisphosphate into fructose 6-phosphateNeed two molecules of pyruvate to generate one glucoseOverall cost of gluconeogenesis2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H+ + 6 H2OGlucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+Go’ = - 38 kJ mol-1Coordinated Reciprocal Regulation of Glycolysis and GluconeogenesisEnergy Status of the cellAndBlood Sugar LevelGlucose metabolismHigh blood [glucose]Low blood [glucose]GlycolysisGlycogen synthesisFA synthesisDecrease blood sugar levelGluconeogenesisGlycogen breakdownTG breakdownInsulinrelease+-+-Glucose metabolismGlucagonreleaseGlycolysisGlycogen synthesisFA synthesisGluconeogenesisGlycogen breakdownTG breakdownIncrease blood sugar levelHigh blood [glucose]Low blood [glucose]Reciprocal regulationFructose 2,6-bisphosphate (F2,6-BP)Phosphofructokinase 2 (PFK2)PFK1Inactivates F1,6-BPaseThe domain structure of the bifunctional regulatory enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphataseThe domain structure of the bifunctional regulatory enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphataseXF2,6BPF6P- Stimulates PFK1 (glycolysis)- Inhibits F1,6-Bisphosphatase (gluconeogenesis)The domain structure of the bifunctional regulatory enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphataseF2,6BPF6P- Glycolysis -Gluconeogenesis XADPLOW BLOOD SUGAR causes phosphorylation of the bifunctional regulatory enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase GlucagonPKAATPPKA inhibits PFK2F2,6BPF6PXHIGH BLOOD SUGAR dephosphorylate the bifunctional regulatory enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphataseXF2,6BPF6PH20Insulin/high F6PPhosphoproteinPhosphatasePiinhibits F2,6BPaseHormonal RegulationGlucagonGlucagon receptorcAMP/PKAEnzyme phosphorylationThe activation of protein kinase A by a G-protein pathwayGlucagon/Glucagon receptor/The regulation of protein kinase A.C = catalytic domainR = regulatory domaininsulinX/glucagon/Glucagon receptorStimulates phosphoprotein phosphataseDephosphorylates PKA substratesGluconeogenesis precursorsThe Cori CycleFate of Pyruvate under ANAEROBIC conditions in animals and other microorganisms: Lactic acid FermentationLactate DehydrogenaseReversible reaction•Generates ATP•Generates anabolic precursors•Lowers blood sugar level•Increases blood sugar level•Uses ATPglycolysis gluconeogenesisBlood sugar too HIGHLow energy charge (Low ATP)Inhibitstimulatesinsulininsulin•Generates ATP•Generates anabolic precursors•Lowers blood sugar level•Increases blood sugar level•Uses ATPglycolysis gluconeogenesisBlood sugar too LOWHIGH energy charge (High ATP)StimulatesInhibitsGlucagonGlucagonSummaryLearn the purpose of each pathway: Determine if +/- by insulin/ glucagon and energy charge (ATP/AMP)Insulin : take glucose out of the bloodGlucagon: adds glucose to the bloodGlycolysis: takes glucose out of the blood makes ATPGluconeogenesis: adds glucose to the blood uses ATPGlucose-6-P is common to several metabolic pathwaysGlycogenGlucoronateGlucosamine-6-phosphateThe Pentose Phosphate Pathway (PPP)Pathways Requiring NADPHSource of biosynthetic reducing power in all organismsSynthesis: Fatty acidCholesterolNeurotransmitterNucleotideDetoxification:Reduction of oxidized glutathioneCytochrome p450 monooxygenaseTwo phases of PPPOxidative phase --- NADPH + Ribulose-5-phosphate(Irreversible)Non-oxidative phase – interconversion of sugars(Reversible)H2O2H+Phase 1: Oxidative phaseIn three irreversible steps(decarboxylase)G-6P Dehydrogenase6-Phosphogluconate DecarboxylasePhase 2: Non-OxidativeRibulose 5-phosphateXylulose 5-phosphateRibose 5-phosphate(Ketopentose)(aldopentose)Phase 2: Non-OxidativeStep 1: IsomerizationSimilar Isomerization – conserved mechanismEpimerization(trans-2,3-enediol intermediate)D37D37D37Nonoxidative phase includes three other reactionsoverallTransketolase Transaldolase Transketolase C5 + C5 C3 + C7C3 + C7 C6 + C4C4 + C5 C6 + C32 (C6 + C3)3 C5Recipient
View Full Document
Unlocking...