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Glycolysis

Glycolysis. Metabolism: Catabolism + Metabolism. Catabolism. Energy-yielding reactions For non-photosynthetic organisms, two sources of fuel Diet Fats, CHO, proteins Stored compounds Fats, starch, glycogen. Catabolism: The Big Picture. Carbohydrate Digestion. Ingested

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Glycolysis

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  1. Glycolysis

  2. Metabolism: Catabolism + Metabolism

  3. Catabolism • Energy-yielding reactions • For non-photosynthetic organisms, two sources of fuel • Diet • Fats, CHO, proteins • Stored compounds • Fats, starch, glycogen

  4. Catabolism: The Big Picture

  5. Carbohydrate Digestion Ingested • Starch, glycogen, cellulose, sucrose, lactose Saliva • -amylase • All (14) split to make D-glucose Stomach • pH low

  6. Carbohydrate Digestion Small intestine • Pancreatic -amylase Brush border (small intestine) • Sucrase: Glc + Fru • Lactase: Glc + Gal

  7. Glycogen Breakdown • Occurs in liver and muscles

  8. Glycogen Breakdown

  9. Glycogen Breakdown

  10. Glycogen Breakdown: Debranching

  11. Glycogen Breakdown: Debranching

  12. Glycogen Breakdown: Debranching

  13. Phosphoglucomutase

  14. Importance of Glycolysis Central energy-yielding path Provides precursors for many biosynthetic paths Overlaps with pyruvate  glucose pathway Illustrates enzyme mechanisms Illustrates regulatory mechanisms

  15. 1st Stage of Glycolysis

  16. Hexokinase Reaction ∆Gº= –16.7 kJ/mol

  17. Hexokinase Reaction • Recall the “induced fit”

  18. Phosphohexose Isomerase • Keto-enol isomerization

  19. Phosphofructokinase (PFK-1) ∆Gº= –14.2 kJ/mol

  20. Phosphofructokinase • Complex enzyme • MW 360,000 • Rate-limiting step in glycolysis • Major control point: allosteric regulation • High ATP inhibits • High AMP, ADP stimulates • Other “fuels” alter activity • Fru-2,6-bisP hormonal signal

  21. Aldolase • Hexose  2 Trioses ∆Gº= +23.8 kJ/mol

  22. Triose Phosphate Isomerase (TPI) ∆Gº= +7.5 kJ/mol

  23. Oxidation of Glyceraldehyde-3-P Otto Warburg 1937-38 ∆Gº= +6.3 kJ/mol

  24. Mechanism of Glyceraldehyde-P DH

  25. Mechanism of Glyceraldehyde-P DH

  26. Mechanism of Glyceraldehyde-P DH

  27. Mechanism of Glyceraldehyde-P DH

  28. Phosphoglycerate Kinase ∆Gº= –18.5 kJ/mol

  29. Phosphoglycerate Mutase A covalent enzyme-phosphate intermediate (P-histidine) is involved, like phosphoglucomutase ∆Gº= +4.4 kJ/mol

  30. Formation of Phosphoenolpyruvate ∆Gº= +7.5 kJ/mol

  31. ATP from PEP: Pyruvate Kinase ∆Gº= –31.4 kJ/mol

  32. Summary of Glycolysis

  33. Side Products of Glycolysis Studies • Discovery of cofactors • ATP • NAD+ • Methods of protein purification • Philosophical change

  34. Side Products of Glycolysis Studies • Understanding of regulation • Demonstration of unity of biochemistry

  35. Glycolysis in Motion: Preparatory Phase Jon Maber Dept of Biochemistry and Molecular Biology The University of Leeds, UK http://bmbwww.leeds.ac.uk/designs/glysteps/home.htm

  36. Glycolysis in Motion: Payoff Phase Jon Maber Dept of Biochemistry and Molecular Biology The University of Leeds, UK http://bmbwww.leeds.ac.uk/designs/glysteps/home.htm

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