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Chapter 14

Chapter 14. Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway Part 1: Glycolysis. Glycolysis. Key topics : Things to Know. Chemistry of each glycolytic reaction: Forwards and Backwards. The general thermodynamics of each reaction. Other sugars entry to glycolysis.

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Chapter 14

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  1. Chapter 14 Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway Part 1: Glycolysis

  2. Glycolysis Key topics: Things to Know • Chemistry of each glycolytic reaction: Forwards and Backwards. • The general thermodynamics of each reaction. • Other sugars entry to glycolysis. • What to do with Pyruvate?

  3. Central Importance of Glucose • Glucose is an excellent fuel • Yields good amount of energy upon oxidation • Can be efficiently stored in the polymeric form • Many organisms and tissues can meet their energy needs on glucose only • Glucose is a versatile biochemical precursor • Bacteria can use glucose to build the carbon skeletons of: • All the amino acids • Membrane lipids • Nucleotides in DNA and RNA • Cofactors needed for the metabolism

  4. Discoverers of Glycolysis (EMP Pathway) Jacob Parnas 1884-1948

  5. Showed that the sugar intermediates were Phosphorylated

  6. Glycolysis Overall 1 Glucose  2 Pyruvates + 2ATP + 2 NADH 10 Reactions: Know them Backwards and Forwards!!!! Where is this going on in a cell? EOC Problems 1+2 can be worked from this Figure and Lactate Dehydrogenase Rxn (slide 35)

  7. Another View of Glycolysis What is This?? from KEGG Pathways Linked to Glycolysis, Enzymes by EC numbers

  8. Human enzymes in green

  9. Hexokinase

  10. PhosphohexoseIsomerase

  11. Phosphofructokinase-1 (PFK-1)

  12. Fructose-1,6-bisphosphate Aldolase

  13. Keep Track of those Carbons! EOC Problem 9..checks out the carbons from triose-phoshpates! Think about the aldolaseΔG.

  14. TIM

  15. 3-P-Gyld DH EOC Problem 14 is about arsenic poisoning and what happens when arsenate is involved with this reaction.

  16. 3-PGA Kinase

  17. 3-PGA Mutase

  18. Enolase is a Dehydrase

  19. Pyruvate Kinase

  20. A Fun Homework Problem • Add up all the ΔG’o ‘s and see how: • Aldolase’s endergonic ΔG is over come. • Total for Glycolysis…what enzymes are doing the work? • But, is that all…what about REALITY? EOC Problem 10: A look at modifying Glycolysis, could it work?

  21. The Real ΔG

  22. Showed cancer cells had high rate of glycolysis, first to crystalize most glycolytic enzymes. Devised the first reliable, quantitative O2 uptake apparatus, lovingly called a Warburg!..but replaced by oxygen electrodes. Nobel Prize, 1931 and trained 6 future Nobel Laureates!! One of which is Hans Krebs who worked out the Citric Acid Cycle.

  23. Medical Aspect: CANCER Most tumors: Glycolysis goes 10X faster than normal cells. And is mainly fermentative (producing lactic acid). The strategy is to: 1. Use this in Detection 2. To slow glycolysis down in cancer cells.

  24. Hypoxia Induced Transcription Factor

  25. Use of 6-Phospho-FdG in Positron Emission Tomography, it accumulates in regions of high glycolytic activity See next slide

  26. CT and PET Scans Patient with malignant melanoma –ingested 6-Phospho-FdG Left-CT scan –shows location of bone, soft tissue Center-PET scan showing high glucose use. Natural areas of high glucose use: brain but not bladder Cancer has spread to liver, muscle Right –false color composite

  27. Type 1 Diabetes and Glycolysis

  28. Entry of other Sugars

  29. Glycogen Phosphorylase

  30. Entry of other Sugars

  31. Conversion of Pyruvate to Something Else

  32. Lactate DH

  33. Why Lactate DH? Consider the Outputs of Catabolism and Needs of Anabolism ! Lactate DH

  34. Alligators do not have a great Cori Cycle

  35. Alcohol Fermentation EOC Problem 4: Calculating the Keq of Alcohol Dehydrogenase (use Table 13-7) EOC Problem 6: follow the carbons from glucose into ethanol.

  36. Entry of Glycerol into Glycolysis

  37. Energetics of Glycerol as An Energy Source Glycerol kinase - ATP Glycerol-3-P DH + NADH 3-P-Gyld DH + NADH 3-PGA Kinase + ATP Pyr Kinase + ATP Total = 1 ATP + 2 NADH Can GLYCEROL be FERMENTED? Explain

  38. Commercial Ethanol Fermentation EOC Problem 7…all about the heat released from fermentation…what’s going on?

  39. Things to Know and Do Before Class Each glycolytic reaction: substrates/products, enzyme name, ΔGs. Keep track of the carbon numbers from glucose to pyruvate. Overall glycolytic ΔG. Getting other sugars and glycerol into glycolysis. EOC Problems: 1, 2, 4-7, 9, 10, 14.

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