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 34Glucose-6-P is common to several metabolic pathwaysSlide 36Slide 37Slide 38Slide 39Slide 40Slide 41Slide 42Slide 43Slide 44Slide 45Slide 46Slide 47Slide 48Slide 49Slide 50Slide 51Slide 52Slide 53Slide 54Slide 55Slide 56Slide 57Slide 58Slide 59Slide 60Learning GoalsLecture 15 –Chapt 16GlycolysisLecture 15 –Chapt 16Glycolysis“Living organisms, like machines, conform to the law of conservation of energy, and must pay for all their activities in the currency of catabolism.”Ernest BaldwinDynamic Aspects of BiochemistryLouie Pasteur’s scientific investigations into fermentation of grape sugar were pioneering studies of glycolysis.1OUTLINEOUTLINE Glycolysis- First phase - Reactions 1-5 (no ATP generated)- Second Phase – Reactions 6-10 (generation of ATP) Feeder pathway to glycolysis (other sugars can also enter the glycolytic pathway) Regulation of glycolysis Glucose transporters Fate of pyruvate under anaerobic conditions- In yeast: Alcohol fermentation-In other microorganisms and exercising muscle: Lactic acid fermentation Hypoxia-Inducible Factor Glycolysis- First phase - Reactions 1-5 (no ATP generated)- Second Phase – Reactions 6-10 (generation of ATP) Feeder pathway to glycolysis (other sugars can also enter the glycolytic pathway) Regulation of glycolysis Glucose transporters Fate of pyruvate under anaerobic conditions- In yeast: Alcohol fermentation-In other microorganisms and exercising muscle: Lactic acid fermentation Hypoxia-Inducible Factor2Metabolic pathways are compartmentalized within cellsMetabolic pathways are compartmentalized within cellsPhase 1Phase 2Glycolysis pathway common to both prokaryotes and eukaryotes. In eukaryotes, glycolysis takes place in cytoplasmGlycolysis pathway common to both prokaryotes and eukaryotes. In eukaryotes, glycolysis takes place in cytoplasm3~ 25 ATPGlucose is converted to glyceraldehyde 3-phosphate (GAP)5 steps: 1. Phosphorylation of glucose2. Isomerization 3. Second phosphorylation of Fructose-6P4. Cleavage into two 3-carbon molecules5. Isomerization of DHAP to GAPGlucose is converted to glyceraldehyde 3-phosphate (GAP)5 steps: 1. Phosphorylation of glucose2. Isomerization 3. Second phosphorylation of Fructose-6P4. Cleavage into two 3-carbon molecules5. Isomerization of DHAP to GAP1st Stage of Glycolysis1st Stage of GlycolysisUses 2 molecules of ATP/glucose but makes no ATP. Traps and prepares glucose for following oxidation stepsUses 2 molecules of ATP/glucose but makes no ATP. Traps and prepares glucose for following oxidation steps4Glycolysis: Reaction 1 - PhosphorylationGlycolysis: Reaction 1 - Phosphorylation+ Mg++ Mg+5ATP + H2O ADP + Pi ∆G°’reaction 1 = -30.5 kJ/molglucose + Pi G-6-P + H2O ∆G°’reaction 2 = +14 kJ/molglucose + ATP G-6-P + ADP ∆G°’overall = -16.5 kJ/molGlucose is kept in the cell by phosphorylation to glucose-6-phosphateGlucose is kept in the cell by phosphorylation to glucose-6-phosphate6HexokinaseHexokinase7Glycolysis: Reaction 2 – Isomerization by phosphoglucose isomeraseGlycolysis: Reaction 2 – Isomerization by phosphoglucose isomerase8Glycolysis: Reaction 3- Second PhosphorylationGlycolysis: Reaction 3- Second PhosphorylationPhosphofructokinase(PFK/PFK1)Phosphofructokinase(PFK/PFK1)9Glycolysis: Reactions 4 – Cleavage of one 6-carbon to two 3-carbon moleculesGlycolysis: Reactions 4 – Cleavage of one 6-carbon to two 3-carbon molecules10Glycolysis: Reactions 5 - end of 1st phase of glycolysisGlycolysis: Reactions 5 - end of 1st phase of glycolysis11GAP is converted to pyruvate:5 steps: 6. Oxidation of GAP to 1,3BPG7. Phosphorylation of ADP8. Mutase9. Dehydration by Enolase10. Phosphorylation of ADP, giving pyruvateGAP is converted to pyruvate:5 steps: 6. Oxidation of GAP to 1,3BPG7. Phosphorylation of ADP8. Mutase9. Dehydration by Enolase10. Phosphorylation of ADP, giving pyruvateSecond Stage of GlycolysisSecond Stage of GlycolysisThe three carbon units are oxidized to pyruvate, generating 4 molecules of ATP/glucose and 2 NADH/glucoseThe three carbon units are oxidized to pyruvate, generating 4 molecules of ATP/glucose and 2 NADH/glucose12Glycolysis Reaction 6 - GAP is oxidized to 1,3-BPGGlycolysis Reaction 6 - GAP is oxidized to 1,3-BPG13∆G°’ = -50 kJ mol-1∆G°’ = -50 kJ mol-1∆G°’ = ~ +56 kJ mol-1∆G°’ = ~ +56 kJ mol-1Uncoupled Oxidation and Phosphorylation ReactionsUncoupled Oxidation and Phosphorylation Reactions14Coupling of the two processes (by one enzyme) allows the conservation of energy released by oxidationCoupling of the two processes (by one enzyme) allows the conservation of energy released by oxidation∆G°’ = +6.3 kJ/mol∆G°’ = +6.3 kJ/mol1516Molecules with High-Phosphoryl Group Transfer PotentialMolecules with High-Phosphoryl Group Transfer PotentialGlycolysis: Reaction 7 (ATP producing reaction)Glycolysis: Reaction 7 (ATP producing reaction)2 ATP consumed in the 1st phase of glycolysis (Reactions 1 and 3) are ‘paid off’ in the this step of the 2nd phase of glycolysis.2 ATP consumed in the 1st phase of glycolysis (Reactions 1 and 3) are ‘paid off’ in the this step of the 2nd phase of glycolysis.2X/glucose2X/glucose2X/glucose2X/glucose17The formation of the high-phosphoryl group transfe rpotential compound 1,3-BPG (in step 6) is essential as a preparation for the ATP production (in step 7).The formation of the high-phosphoryl group transfe rpotential compound 1,3-BPG (in step 6) is essential as a preparation for the ATP production (in step 7).GAP 1,3-BPG 3 PGPreparative step for ATP production in the following stepATPStep 6Step 7Actual ATP productionThermodynamically favorable Reactions 7 drives the less favorable Reaction 6Thermodynamically favorable Reactions 7 drives the less favorable Reaction 6∆G°’ = +6.3 kJ/mol∆G°’ = +6.3 kJ/mol∆G°’ = -49.6 kJ/mol∆G°’ = -49.6 kJ/mol30.5 kJ/mol-18.9 kJ/mol18Compound with High-Phosphoryl Group Transfer PotentialGlycolysis: Reaction 8 – Phosphoglycerate MutaseGlycolysis: Reaction 8 – Phosphoglycerate Mutase(Note: The term Mutase is applied to those
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