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Possible fates of glucose

Possible fates of glucose. Glycolysis glykys = sweet, lysis =splitting; degradation of glucose the process of the largest carbon flux in most cells sole energy source for many kinds of cells (e.g. erythrocytes, brain, renal medulla, sperm )

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Possible fates of glucose

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  1. Possible fates of glucose

  2. Glycolysis • glykys= sweet, lysis=splitting; degradation of glucose • the process of the largest carbon flux in most cells • sole energy source for many kinds of cells (e.g. erythrocytes, brain, renal medulla, sperm) • anaerobic microorganisms are entirely dependent on glycolysis (e.g. Clostridium tetani - tetanus (lockjaw)Clostridium botulinum - botulismBacterides fragilis - various types of infection) • the enzymes involved are almost completely conserved from yeast to human

  3. 1 activation and trapping

  4. 2 See animated mechanism at Lehninger website

  5. 3 The first committed step of glycolysis

  6. PFK-1: the most important control element since it catalyses the committed step

  7. ATP inhibits PFK-1 ATP/AMP decreases  activity increases citrate inhibits PFK-1, too F-2,6-BP is anallosteric activator

  8. PFK-2 is in the same enzyme asFBPase2

  9. Metabolic Control Analysis Flux concentration More info on MCA: http://bip.cnrs-mrs.fr/bip10/mcafaq.htm (English)

  10. 4

  11. 5

  12. 6 The essential role of inorganic phosphate (Pi)

  13. 7 Substrate levelphosphorylation

  14. 8 Requires traces of 2,3-BPG

  15. 9

  16. 10

  17. All intermediates of glycolysis are phosphorylated • they cannot leave the cell(negative charge, lack of transporters; concentration gradient) • energy is conserved(phosphorylation potential of ATP is not lost completely) • enzymes are phosphorylated at their active sites(phosphorylation  rearrangement  decrease of the activation barrier AND increase of specificity) • Mg2+ is necessary for each steps

  18. Energy balance of glycolysis Glc + 2 NAD+ + 2 ADP + 2 Pi 2 Pyr + 2 NADH + 2 H+ + 2 ATP + 2 H2OG’° = -85 kJ/mol Glc + 2 NAD+  2 Pyr + 2 NADH + 2 H+ G’° = -146 kJ/mol and it is only a small fraction of total available energy of the glucose molecule! (see TCA cycle later) 2 ADP + 2 Pi 2 ATP + 2 H2O G’° = 61 kJ/mol See also:http://bcs.whfreeman.com/biochem5Ch 16, Conceptual Insights “Energetics of Glucose Metabolism”

  19. “Essentially irreversible” reactions in glycolysis

  20. Regulation on short time-scale: PFK-1, Hexokinase, Pyruvate kinase • Regulation on longer time-scales: • glucagon • epinephrine • insulin • HIF-1 Glucose transport into cells: GLUTx

  21. Anabolic reactions

  22. Online resources: http://bcs.whfreeman.com/lehninger (Ch14, Ch15) http://bcs.whfreeman.com/biochem5 (Ch16) For online quizzing give: zoltan.berente@aok.pte.hu as instructor’s e-mail address

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