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SURVEY OF BIOCHEMISTRY Glycolysis

SURVEY OF BIOCHEMISTRY Glycolysis. Glycolysis Overview. Glycolysis: breakdown of glucose into pyruvate with net production of ATP Occurs in cytosol. Glucose + 2 ADP + 2 NAD + + 2 P i 2 Pyruvate + 2 ATP + 2 NADH + 2 H +. 10 steps. Glycolysis: First 5 Steps. Convert Glucose into G6P

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SURVEY OF BIOCHEMISTRY Glycolysis

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  1. SURVEY OF BIOCHEMISTRYGlycolysis

  2. Glycolysis Overview • Glycolysis: breakdown of glucose into pyruvate with net production of ATP • Occurs in cytosol Glucose + 2 ADP + 2 NAD+ + 2 Pi 2 Pyruvate + 2 ATP + 2 NADH + 2 H+ 10 steps

  3. Glycolysis: First 5 Steps • Convert Glucose into G6P • Convert G6P into F6P • Convert F6P into FBP • Split FBP into two molecules • GAP: ready for next step • DHAP: must convert into GAP before proceeding

  4. Drawing Glucose Draw the molecule glucose in the Haworth projection • Start with the ring system 5 4 1 3 2

  5. Drawing Glucose Draw the molecule glucose in the Haworth projection • Start with the ring system • Add the substituents on the ring system • C1 - draw OH down • C2 - draw OH down • C3 - draw OH up • C4 - draw OH down • C5 - draw CH2OHup 6 5 4 1 2 3

  6. Glycolysis: Step #1 Kinases transfer PO32- groups from one molecule to another Mg2+ Hexokinase Reaction mostly proceeds to the right

  7. Glycolysis: Step #2 Phosphoglucose Isomerase (PGI) converts G6P into a fructose-based molecule through acid-base catalysis Let’s look at this mechanism more closely…

  8. PGI Reaction Mechanism

  9. PGI Reaction Mechanism BaseCatalysis

  10. PGI Reaction Mechanism AcidCatalysis

  11. PGI Reaction Mechanism Base catalyzes ring closure H+

  12. 6 1 5 2 3 4 Practice Drawing Fructose 6-Phosphate Begin with the ring system

  13. 6 1 5 2 3 4 Practice Drawing Fructose 6-Phosphate Add Substitutents C1 = CH2OH drawn up C2 - draw OH down C3 - draw OH up C4 - draw OH down C6 = CH2OPO32- drawn up Begin with the ring system

  14. Glycolysis: Step #3 Phosphofructokinase transfers PO32- group from ATP to fructose-6-phosphate PFK + ADP + H+ So far, 2 ATP molecules have been invested in glycolysis!

  15. Drawing FBP Recall from Ch. 8 Haworth and Fischer projections are equivalent

  16. Glycolysis: Step #4 Aldolase Aldolase is unique in glycolysis; it cleaves FBP into two 3-C molecules - GAP and DHAP Let’s see how aldolase works…

  17. Aldolase Rxn Mechanism Aldolase binds to the substrate Fructose-1,6-Bisphosphate

  18. Aldolase Rxn Mechanism

  19. Aldolase Rxn Mechanism

  20. Aldolase Rxn Mechanism

  21. Aldolase Rxn Mechanism H2O Aldolase cleaves FBP into GAP and DHAP

  22. Glycolysis: Step #5Triose Phosphate Isomerase DHAP must be converted intoGAP via the enzyme triose phosphate isomerase (TIM) to proceed through glycolysis

  23. Overview After Step 5 Two molecules of ATP are invested initially. One molecule of glucose gets metabolized into 2 molecules of GAP

  24. Next Week… • Steps #6-10 of glycolysis • Overview of bioenergetics from glycolysis • More on enzymes in glycolysis

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