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Chapter 17 Glycolysis

Chapter 17 Glycolysis. Plays a key role in energy metabolism by providing significant portion of energy utilized by most organisms. Glucose + 2 NAD + + 2 ADP + 2 Pi 2 Pyruvate + 2 NADH + 2 ATP. Ethanol Fermentation. Lactic Acid Fermentation. From Lehninger Principles of Biochemistry.

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Chapter 17 Glycolysis

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  1. Chapter 17 Glycolysis • Plays a key role in energy metabolism by providing significant portion of energy utilized by most organisms Glucose + 2 NAD+ + 2 ADP + 2 Pi 2 Pyruvate + 2 NADH + 2 ATP

  2. Ethanol Fermentation Lactic Acid Fermentation From Lehninger Principles of Biochemistry

  3. Degradation of glucose via the glycolytic pathway Stage I: Reactions 1 – 5 Stage II: Reactions 6 – 10

  4. From Lehninger Principles of Biochemistry

  5. From Lehninger Principles of Biochemistry

  6. glucose glucose 6-phosphate fructose 6-phosphate fructose 1,6-bisphosphate glyceraldehyde 3-phosphate + dihydroxyacetone phosphate C6H7O(OH)5 = C6H12O6 Non-Redox -OH + OPO32- isomerization -OH + OPO32- C6H7O(OH)3(OPO32-) 2 = C6H10O4(OPO32-) 2 cleavage 2 C3H5O2(OPO32-) From Lehninger Principles of Biochemistry

  7. Step 1: Phosphorylation of Glucose Nucleophilic attack of the C6 –OH group of glucose on the g phosphate of an Mg-ATP .. First ATP Utilization Kinase: Enzyme that transfers phosphoryl groups between ATP & metabolite From Lehninger Principles of Biochemistry

  8. Yeast Hexokinase without glucose Yeast Hexokinase with glucose 2 lobes come together to engulf the substrate

  9. Induced Fit in Hexokinase Closing of the 2 lobes places ATP in close proximity to the C6 –OH group & excludes water from the active site D-glucose Glucose induces a large conformational change in hexokinase Substrate induced conformational change is responsible for the enzyme’s specificity From Lehninger Principles of Biochemistry

  10. Step 2: Conversion of glucose 6-phosphate to fructose 6-phosphate From Lehninger Principles of Biochemistry

  11. Reaction mechanism of phosphoglucose isomerase The active site catalytic residues BH+ Lys B’ His-Glu dyad

  12. Step 3: Phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate Second ATP utilization From Lehninger Principles of Biochemistry

  13. Step 4: Cleavage of fructose 1,6-bisphosphate Mechanism of base-catalyzed aldol cleavage Aldol condensation occurs by the reverse mechanism

  14. Enzymatic mechanism of class I aldolase

  15. From Lehninger Principles of Biochemistry

  16. From Lehninger Principles of Biochemistry

  17. From Lehninger Principles of Biochemistry

  18. Step 5: Interconversion of the triose phosphates From Lehninger Principles of Biochemistry

  19. From Lehninger Principles of Biochemistry

  20. Redox 1,3-bisphosphoglycerate 3-phosphoglycerate glyceraldehyde 3-phosphate pyruvate 2-phosphoglycerate phosphoenolpyruvate From Lehninger Principles of Biochemistry

  21. NAD+/NADH From Lehninger Principles of Biochemistry

  22. NAD+ + H -NADH or NAD+ + H + + 2e- NADH Step 6: Oxidation of glyceraldehyde 3-phosphate to 1,3 bisphosphoglycerate Compound with high phosphate group-transfer potential • NAD+ is the primary oxidizing agent of glycolysis • If NAD+ runs out, glycolysisstops! From Lehninger Principles of Biochemistry

  23. The enzymatic mechanism of glyceraldehyde 3-phosphate dehydrogenase NAD+ is the oxidizing agent Substrate is oxidized Sulfhydryl group

  24. Step 7: Phosphoryl transfer from 1,3-bisphosphoglycerate to ADP First ATP generation From Lehninger Principles of Biochemistry

  25. Yeast phosphoglycerate kinase (bilobal structure) Upon substrate binding the 2 domains of PGK swing together so as to permit the substrates to react in a water free environment (as occurs with hexokinase)

  26. Step 8: Conversion of 3-phosphoglycerate to 2-phosphoglycerate From Lehninger Principles of Biochemistry

  27. A proposed reaction mechanism for phosphoglycerate mutase

  28. Step 9: Dehydration of 2-phosphoglycerate to phosphoenolpyruvate From Lehninger Principles of Biochemistry

  29. Step 10: Transfer of a phosphoryl group from PEP to ADP From Lehninger Principles of Biochemistry

  30. Phosphoenolpyruvate , PEP From Lehninger Principles of Biochemistry

  31. Standard state conditions Reactions 1-10 are glucose to pyruvate and reaction 11 is pyruvate to lactate. At concentrations in RBC From Lehninger Principles of Biochemistry

  32. Glycolysis does not require O2 from air, but it does require the oxidant NAD+ Ethanol fermentation in yeast and other microorganisms Lactic acid fermentation in several types of animal cells and some microorganisms From Lehninger Principles of Biochemistry

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