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Understanding the Warburg Effect and Glycolysis in Cancer Metabolism

This session focuses on the Warburg Effect, the observation that most cancer cells primarily generate energy through glycolysis followed by lactic acid fermentation, a key concept linked to cancer metabolism. We will explore the role of glycolytic enzymes, lactate dehydrogenase (LDH), and the pentose phosphate pathway in energy production and metabolic regulation. Join us during office hours to discuss these concepts further, and refer to the detailed course content available on the course website for a deeper dive into these essential biochemical processes.

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Understanding the Warburg Effect and Glycolysis in Cancer Metabolism

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  1. Start (or continue) going to TA sections Come to R’s and/or TAs office hours 2130 Pac Hall Tu2:30-3:30 W 2:30-3:30 details on course web site: http://course.ucsd.edu/rhampton/bibc102

  2. Warburg Effect the Warburg effect is the observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol Otto Heinrich Warburg 1931 Nobel Prize in Medicine

  3. Warburg Effect

  4. Getting other sugars into the glycolytic pathway fig 14-10

  5. A second route for fructose (in liver) pg 545

  6. Glycogen: nature’s sugar bowl

  7. Liberating glucose units from glycogen more about glycogen later fig 14-11

  8. From glycogen to glycolysis… phosphogluco- mutase another mutase…

  9. Now what? fig 14-1

  10. Now what? fig 14-1

  11. Now what? Fermentation: anaerobic metabolism of glucose without oxidation... fig 14-1

  12. LDH converts pyruvate to lactate, restoring the pool of NAD+ pg 547

  13. LDH converts pyruvate to lactate, restoring the pool of NAD+ pg 547

  14. ethanol production: another NAD+ restoration strategy pg 547

  15. Thiamine pyrophosphate (TPP): an activated carbon fig 14-14

  16. Thiamine pyrophosphate in ethanol production fig 14-14

  17. TPP as a carbanion nucleophile in pyruvate metabolism fig 14-14

  18. TPP as a carbanion nucleophile in pyruvate metabolism fig 14-14

  19. TPP as a carbanion nucleophile in pyruvate metabolism fig 14-14

  20. TPP-mediated enzymatic reactions TPP is all about carbonyl activation table 14-1

  21. The glycolysis energy landscape (pyruvate set to 0)

  22. Regulated glycolytic enzymes hexokinse (and glucokinse) regulated by G6P allosterically liver isozyme is glucokinase, different phosphofructokinase (PFK-1) pyruvate kinase regulated by ATP, citrate, and fatty acids

  23. The glycolysis energy landscape (pyruvate set to 0)

  24. regulation of hexokinase: isozymes can differ fig 15-12

  25. PFK-1 : a right fancy enzyme! fig 15-14

  26. PFK-1: allosteric regulation by ATP, etc… fig 15-14

  27. PFK-1: allosteric regulation by ADP, etc… xxx

  28. FPK-1 has multiple allosteric regulators fig 15-14

  29. Our book’s notation for regulators inhibition activation fig 15-14

  30. PFK-1 has multiple allosteric regulators fig 15-14

  31. Ask… or txt: 858 914 4945

  32. Pentose phosphate pathway oxidative reactions Glucose as a source of other stuff fig 14-21

  33. Pentose phosphate pathway oxidative reactions fig 14-21

  34. Pentose phosphate pathway oxidative reactions fig 14-21

  35. Pentose phosphate pathway oxidative reactions fig 14-21

  36. Pentose phosphate pathway: non-oxidative rxns all movement of carbonyl groups to and fro… fig 14-22

  37. Pentose phosphate pathway: non- oxidative reactions 2C 3C 2C 2C 2C 3C fig 14-22 end of lecture 6

  38. LDH converts pyruvate to lactate, restoring the pool of NAD+ pg 547

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