Glycolysis amp Gluconeogenesis Glycolysis and Catabolism Glycolysis is a sequence of enzymecatalyzed reaction by which glucose is converted into pyruvate Pyruvate can be further aerobically oxidized ID: 1012204
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1. BiochemistryLecture 12Glycolysis & Gluconeogenesis
2. Glycolysis and CatabolismGlycolysis is a sequence of enzyme-catalyzed reaction by which glucose is converted into pyruvatePyruvate can be further aerobically oxidizedPyruvate can be used as a precursor in biosynthesis
3. Central Importance of GlucoseGlucose is an excellent fuelYields good amount of energy upon oxidation(-2840 kJ/mole)Can be efficiently stored in the polymeric form Many organisms and tissues can meet their energy needs on glucose onlyGlucose is a versatile biochemical precursorBacteria can use glucose to build the carbon skeletons of:All the amino acidsMembrane lipidsNucleotides in DNA and RNACofactors needed for the metabolism
4. Feeder Pathways for GlycolysisIngested disaccharides are hydrolyzed lactose: glucose and galactosesucrose: glucose and fructosefructose, galactose and mannose enter glycolysis at different pointsGlucose molecules are cleaved from glycogen and starch by glycogen phosphorylaseyields glucose-1-phosphate4
5. Glycogen Breakdown5
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12. Phosphohexose Isomerase Mechanism
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15. Aldolase Mechanism
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20. Electron Carriers20
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26. How does food enter this process?
27. Anaerobic Exercise
28. “Anaerobic Exercise” in Yeast
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30. Regulating GlycolysisDifferent levels of control have different response times:Level of ControlResponse TimeAllostericmillisecondsPhosphorylationsecondsTranscriptionalhours30
31. Fates of Pyruvate31
32. Ethanol Production (Anaerobic)32
33. Lactic Acid Fermentation (Anaerobic)Our muscles can function without oxygen for a short period of time by converting pyruvate to lactate and NAD+, which allows glycolysis to continue33
34. Gluconeogenesis
35. Glycolysis vs. GluconeogenesisGlycolysis occurs mainly in the muscle, RBCs and brainGluconeogenesis occurs mainly in the liver and kidneysGluconeogenesis is similar to glycolysis (but is not a reversal)Different in the three regulatory steps of glycolysis:hexokinasePFK-1pyruvate kinase35
36. GluconeogenesisMetab1 ABMetab2XY-Metabolic Pathways are Irreversible ∆G between the 1st & last metabolite is large & neg. - If 2 metabolites are interconvertible (metab 1 metab 2), the path from Metab 1 Metab 2 must be different from that of Metab 2 Metab 1
37. Free-Energy Changes in GlycolysisDG°’Only large for steps 1, 3, and 10: these steps are metabolically irreversible & regulatedDG ~ 0: steps are near equilibrium37
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43. Dephosphorylation is not phosphorylation in reverse!Reverse Phosphorylation of ADP by F1,6 BP to generate F6P (and ATP) would be steeply uphill:F1,6 BP + ADP F6P + ATP ∆G° = +3.4 kcal/mol Instead, dephosphorylation is carried out: F1,6 BP + H2O F6P + PO4 ∆G° = -3.9 kcal/mol Reverse Phosphorylation would be mediated by PFK Dephosphorylation is mediated by F1,6BPaseB. Circumventing PFK – dephosphorylation of F1,6BP
44. C. Circumventing Hexokinase – dephosphorylation of G6PMediated by G6PaseG6Pase is present only in liver and kidneyHence, these are the only tissues that can synthesize and secrete glucose into the blood
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47. HexokinaseIsozymes are different enzymes that catalyze the same reactionThey typically share similar sequencesTheir regulation is often different
48. Peg. G6P is structurally similar to glucose, and competes with glucose for active site of hexokinase
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51. ATP/AMP Allosteric Site in PFK51
52. Fructose-2,6-bisphosphate
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57. Two Alternative Fates for PyruvatePyruvate can be a source of new glucoseStore energy as glycogenGenerate NADPH via pentose phosphate pathwayPyruvate can be a source of acetyl-CoAStore energy as body fatMake ATP via citric acid cycleAcetyl-CoA stimulates glucose synthesis by activating pyruvate carboxylase
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59. PancreasGlucagonLiverGlycogenGlucoseF6PF1,6BPPyruvatePKF2,6BPPFKGlucose(Blood)BrainEpinephrineAdrenal MedullaGlucoseMuscleGlycogenF6PF2,6BPPFKF1,6BPPyruvatePK++++++++