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Glucose Utilization

Glucose Utilization. Metabolic Mainstreet. Glucose. Glycolysis. Pyruvate. Bridging Rx. AcetylCoA. NAD + /FAD. NADH/FADH 2. C 6. C 4. OP. Krebs Cycle. ADP O 2. C 5. C 4. ATP. PATHWAYS: 4 W’s. W hat = Net Reaction. W hy = Purpose(s) of Pathway.

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Glucose Utilization

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  1. Glucose Utilization

  2. Metabolic Mainstreet Glucose Glycolysis Pyruvate Bridging Rx. AcetylCoA NAD+/FAD NADH/FADH2 C6 C4 OP Krebs Cycle ADP O2 C5 C4 ATP

  3. PATHWAYS: 4 W’s What = Net Reaction Why = Purpose(s) of Pathway Where = Organism/Tissue/Organelle When = Regulation of Pathway

  4. GLYCOLYSIS: Net Reaction (What) GLUCOSE + 2ADP + 2NAD+ 10 Enzymes 2PYRUVATE + 2ATP + 2NADH Glucose gets oxidized - NAD+ gets reduced Two ADP molecules get phosphorylated Glycolysis is a a) catabolic b) anabolic pathway? Do bacteria have a glycolysispathway? a) yes b) no c) only anaerobic bacteria

  5. GLYCOLYSIS: Purpose (Why) 1. Generate ATP a. immediate (2 “anaerobic” ATP) b. future - more ATP from pyruvate & NADH 2. Provide intermediates/pyruvate for synthesis reactions Where? When? All Organisms: bacteria, plants, animals Low Energy Charge phosphofructokinase (-) ATP hexokinase (-) G-6-P pyruvate kinase (-) ATP All Cell Types: liver, muscle, brain, adipose, etc. Cytoplasm

  6. OH O HO OH OH OH OH O OH HO OH OH CH2 – OH | CH – OH | CH2 – OH glycerol CHO | CH – OH | CH2 – OH glyceraldehyde COO- | CH – OH | CH2 – OH glycerate a - Glucose b - Fructose

  7. COO- | CH – OH | CH2 – O - PO32- Name this molecule. a) Glycerol phosphate b) Glyceraldehyde 3 phosphate c) 3 – phosphoglycerate d) 1 - phosphoglycerate

  8. COO- | C=O | CH3 pyruvate COO- | C-OH || CH2 enol pyruvate CH2 - OH | C=O | CH2 - OH Dihydroxy acetone

  9. GLYCOLYSIS Glucose Glucose-6-Phosphate Fructose-6-Phosphate Fructose 1,6 Bisphosphate DHAP + Glyceraldehyde-3-P Pyruvate PEP 2-Phosphoglycerate 3-Phosphoglycerate 1,3-BPG Glyceraldehyde-3-P

  10. Glucose in 2 ATP → 2 ADP C6→ 2C3 2 NAD+ reduced → 2 NADH 4 ADP → 4 ATP 2 pyruvate out

  11. Glycolysis: The Preparatory Phase

  12. Glycolysis: The Payoff Phase

  13. fuel in GLYCOLYSIS: Net Reaction (What) SH2NADH ATP S NAD+ADP work output GLUCOSE + 2ADP + 2NAD+ 10 Enzymes 2PYRUVATE + 2ATP + 2NADH Glucose gets oxidized - NAD+ gets reduced Two ADP molecules get phosphorylated What is the limiting reagent for glycolysis? a) Glucose b) ADP c) NAD+

  14. Aerobic ~ 36 ATP Metabolic Mainstreet Glucose NAD+ Glycolysis NADH Pyruvate Bridging Rx. Lactate AcetylCoA NADH/FADH2 How do you supply NAD+ to glycolysis When a lack of O2 Prevents OP! C6 C4 OP Krebs Cycle ADP O2 C5 C4 ATP

  15. Lactate GLYCOLYSIS: Anaerobic GLUCOSE + 2ADP + 2NAD+ 10 Enzymes 2PYRUVATE + 2ATP + 2NADH COO- | NAD++ H - C - OH | CH3 COO- | C = O + NADH | CH3 Muscle Liver Lactate Dehydrogenase (LDH)

  16. GLYCOLYSIS : Side Reactions Glucose Glucose-6-Phosphate  Glycogen  R-5-P/Glucose Fructose-6-Phosphate 2,3 BPG Fructose 1,6 Bisphosphate DHAP + Glyceraldehyde-3-P Pyruvate PEP 2-Phosphoglycerate  3-Phosphoglycerate 1,3-BPG  Glycerol Glyceraldehyde-3-P

  17. GLYCOLYSIS: Regulation Glucose (-) G-6-P 2nd Glucose-6-Phosphate  Glycogen Fructose-6-Phosphate (-) ATP 1st Fructose 1,6 Bisphosphate DHAP + Glyceraldehyde-3-P Pyruvate (-) ATP PEP 2-Phosphoglycerate 3-Phosphoglycerate 1,3-BPG Glyceraldehyde-3-P

  18. E P Metabolic Regulation 1. How Much Enzyme - Regulation of gene expression 2. Activity of Available Enzyme Allosteric Enzymes Covalent Modifications Proenzymes S Conditions in the cell (Goldilocks and the three Bears) a) Too much P – slow down pathway b) Too little P – speed up pathway c) [P] is just right – maintain steady state

  19. Allosteric Enzymes R state (relaxed) – active: S → P T state (tense) – inactive (or less active): very little P formed T↔ R + S ↔ R + P A negative regulator (-) will bind selectively to the less active form of an enzyme, shifting the conformational equilibrium toward this form and decreasing activity. [T] increases and [R] decreases T-↔(- regulator) + T↔ R + S ↔ R + P A positive regulator (+) will bind selectively to the more active form of an enzyme, shifting the conformational equilibrium toward this form and increasing activity. [T] decreasesand [R] increases T↔ R + S ↔ R + P + (+ regulator)↔ R++ S

  20. GLYCOLYSIS: Regulation Glucose (-) G-6-P 2nd Glucose-6-Phosphate  Glycogen Fructose-6-Phosphate (-) ATP 1st Fructose 1,6 Bisphosphate DHAP + Glyceraldehyde-3-P Pyruvate (-) ATP PEP 2-Phosphoglycerate 3-Phosphoglycerate 1,3-BPG Glyceraldehyde-3-P

  21. 1 (-) G-6-P 3 (-) ATP

  22. Phosphofructokinase has distinct active and allosteric sites ATP is a negative allosteric regulator Muscle (M4) - ↑ATP decreases PFK activity

  23. Liver Glycolysis Regulation ↑Liver Glycolysis ↓Liver Glycolysis 3 days Long Term Fast Liver Gluconeogenesis provides glucose to blood/brain. Liver Glycogenolysis provides glucose to blood/brain.

  24. Liver (L4) - ↑ATP decreases PFK activity ↑ F-2,6-bP blocks ATP allosteric effect and S cooperativity ↑[citrate] also enhances ATP (-) effect (signals sufficient building blocks) The liver runs glycolysis in the Fed state and blocks glycolysis in the Fasting State. This initially seems counterintuitive …….

  25. GLUCONEOGENESIS ― What? to blood 2Pyruvate + 4ATP + 2NADH 2GTP Glucose + 4ADP + 2NAD+ 2GDP Where? Liver Why? To maintain blood [glucose] after glycogen is used up When? Fasting state – (particularly late fast) ↑ [acetylCoA] and glucagon

  26. Gluconeogenesis 3 days Long Term Fast Liver Gluconeogenesis provides glucose to blood/brain.

  27. Metabolic Mainstreet Glucose Glycolysis Pyruvate Bridging Rx. AcetylCoA NAD+/FAD NADH/FADH2 C6 oxaloacetate OP Krebs Cycle ADP O2 C5 C4 ATP

  28. Gluconeogenesis - Bypass Enzymes Glucose oxaloacetate Glucose-6-Phosphate Fructose-6-Phosphate Fructose 1,6 Bisphosphate DHAP + Glyceraldehyde-3-P Pyruvate PEP 2-Phosphoglycerate 3-Phosphoglycerate 1,3-BPG Pyruvate carboxylase PEP carboxykinase Glucose 6- phosphatase Fructose 1,6-bis phosphatase Glyceraldehyde-3-P

  29. 10. Pyruvatecarboxylase & PEP carboxykinase (+) acetylCoA & (-) ADP pyruvate + CO2 + ATP + H2O  oxaloacetate + ADP,Pi + 2H+ oxaloacetate + GTP  PEP + GDP + CO2 • Fructose 1,6-bisphosphatase • (-) fructose 2,6-bisphosphate (low fasting – high Fed) • (-) AMP fructose 1,6 bisphosphate + H2O  fructose 6-phosphate + Pi 1. Glucose 6-phosphatase glucose 6-phosphate + H2O  glucose + Pi Gluconeogenesis - Bypass Enzymes

  30. Pyruvate Oxaloacetate DHAP Glucose Lactate Amino Acids Glycerol Where does Pyruvate come from?

  31. Metabolic Mainstreet & fasting state Protein Glucose Glycolysis Pyruvate Fat Bridging Rx. amino acids AcetylCoA Fatty acids NAD+/FAD Transamination & oxidative deamination NADH/FADH2 C6 oxaloacetate OP Krebs Cycle ADP O2 C5 C4 ATP

  32. Glycolysis Fed State insulin Liver Regulation Gluconeogenesis Fasting State glucagon (-) ATP (-) citrate (+) F-2,6 BP (+) AMP phosphofructokinase Fructose-6-Phos Fructose 1,6 Bisphos (-) AMP (-) F-2,6 BP (+) citrate Fructose 1,6-bisphosphatase (-) ADP PEP carboxykinase PEP Pyruvate (-) ATP (-) Alanine (+) F-1,6 BP Pyruvate kinase oxaloacetate (-) ADP (+) AcetylCoA Pyruvate carboxylase

  33. Cori Cycle : Recycling Lactate Liver Muscle Glycogen Glycogen Glucose Lactate Glucose Lactate

  34. Pentose Phosphate Pathway

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