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GLYCOLYSIS

GLYCOLYSIS. GLUCOSE TRANSPORTERS. METABOLIC FATES OF GLUCOSE. Catabolized to produce ATP Stored as glycogen in liver and muscles Converted to fatty acids and stored as triglycerides in adipose tissue. CARBOHYDRATE CATABOLISM. GLYCOLYSIS. A two-phase pathway in which

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GLYCOLYSIS

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  1. GLYCOLYSIS

  2. GLUCOSE TRANSPORTERS

  3. METABOLIC FATES OF GLUCOSE • Catabolized to produce ATP • Stored as glycogen in liver and muscles • Converted to fatty acids and stored as triglycerides in adipose tissue

  4. CARBOHYDRATE CATABOLISM

  5. GLYCOLYSIS • A two-phase pathway in which • Glucose is oxidized into pyruvate • NAD+ is reduced to NADH + H+ • ATP is synthesized by substrate-level phosphorylation Pyruvate • Moves on to the Krebs cycle in an aerobic environment • Is reduced to lactate in an anaerobic environment

  6. Glucose 2 ATP Fructose 1,6-bisphosphate 4 ATP 2 NADH 2 Pyruvate GLYCOLYSIS – The phases I. Energy investment phase II. Energy generation phase

  7. ATP ADP GLUCOSE 6- PHOSPHATE Hexokinase Glucokinase GLYCOLYSISStep I. GLUCOSE

  8. Hexokinase/Glucokinase Hexokinase • Found in most tissues • Broad specificity • Low Km • Low Vmax Makes glucose available to tissues at low blood glucose levels

  9. Hexokinase/Glucokinase • Glucokinase • Found in liver and b cells of pancreas • Broad specificity • High Km • High Vmax • Clears glucose from blood after meals and at blood glucose levels > 100 mg/dl

  10. FRUCTOSE 6- PHOSPHATE Phosphoglucose isomerase GLYCOLYSISStep II. GLUCOSE 6- PHOSPHATE

  11. ATP ADP FRUCTOSE 1, 6- BISPHOSPHATE Phosphofructo-kinase I GLYCOLYSISStep III. FRUCTOSE 6- PHOSPHATE

  12. DIHYDROXACETONE PHOSPHATE Aldolase GLYCERALDEHYDE 3-PHOSPHATE GLYCOLYSISSteps IV, V. Triose phosphate isomerase FRUCTOSE 1, 6- BISPHOSPHATE

  13. NAD+ NADH + H+ Pi 1,3- BISPHOSPO-GLYCERATE Glyceraldehyde 3-phosphate dehydrogenase GLYCOLYSISStep VI. GLYCERALDEHYDE 3-PHOSPHATE

  14. ATP ADP 3- PHOSPHO-GLYCERATE Phosphoglycerate kinase GLYCOLYSISStep VII. 1,3- BISPHOSPHO-GLYCERATE

  15. SUBSTRATE-LEVEL PHOSPHORYLATION High-energy phosphate groups are transferred directly from phosphorylated substrates to ADP

  16. ATP ADP 1,3- BISPHOSPHO-GLYCERATE 3- PHOSPHO-GLYCERATE Phosphoglycerate kinase P-OH Phosphatase Mutase 2, 3- BISPHOSPHO-GLYCERATE H2O 2, 3- BISPHOSPHOGLYCERATE

  17. ARSENATE POISONING GLYCERALDEHYDE 3-PHOSPHATE Pi Pi ARSENATE Glyceraldehyde 3-phosphate dehydrogenase NAD+ GLYCOLYSIS CONTINUES… ENERGY IS DEPLETED H+ + NADH 1,3- BISPHOSPOGLYCERATE ADP ATP 3- PHOSPHOGLYCERATE

  18. 2- PHOSPHO-GLYCERATE Phosphoglycerate mutase GLYCOLYSISStep VIII. 3- PHOSPHO-GLYCERATE

  19. H2O PHOSPHOENOLPYRUVATE Enolase GLYCOLYSISStep IX. FLOURIDE 2- PHOSPHO-GLYCERATE

  20. ATP ADP PYRUVATE Pyruvate kinase GLYCOLYSISStep X. PHOSPHOENOLPYRUVATE

  21. GLYCOLYSIS: SUMMARY GLUCOSE + 2NAD+ +2Pi + 2ADP 2 PYRUVATE + 2NADH + 2H+ + 2ATP + 2H2O

  22. THE FATES OF PYRUVATE • ANAEROBIC CONDITIONS Reduced to lactate (In RBCs, the kidney medulla, lens and cornea of the eye, testes, leukocytes and in muscles during intensive exercise) • AEROBIC CONDITIONS oxidative decarboxylation to Acetyl CoA (in tissue with high oxidative capacity e.g. cardiac muscle, brain etc. )

  23. 1,3- BISPHOSPHO-GLYCERATE GLYCERALDEHYDE 3-PHOSPHATE NADH + H+ NAD+ LACTATE lactatedehydrogenase ANAEROBIC CONDITIONS PYRUVATE

  24. ANAEROBIC GLYCOLYSIS GLUCOSE + 2Pi + 2ADP 2 Lactate + 2ATP + 2H2O + 2H+

  25. NADH + H+ NAD CoA-SH ACETYL CoA Pyruvate dehydrogenase complex (E1 + E2 + E3) AEROBIC GLYCOLYSIS PYRUVATE

  26. For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle

  27. REGULATION OF GLYCOLYSIS • Hexokinase/Glucokinase • Phosphofructokinase • Pyruvate Kinase

  28. _ REGULATION OF HEXOKINASE GLUCOSE ATP Hexokinase ADP GLUCOSE 6- PHOSPHATE

  29. REGULATION OF GLUCOKINASE + _ GLUCOSE ATP Glucokinase ADP GLUCOSE 6- PHOSPHATE FRUCTOSE 6- PHOSPHATE

  30. REGULATION OF GLUCOKINASE ATP ADP GLUCOSE 6- PHOSPHATE GLUCOSE Glucokinase Glucokinase Nucleus GKRP GK FRUCTOSE 6- PHOSPHATE

  31. _ ATP, CITRATE + AMP, Fructose 2,6 bisphosphate REGULATION OF PHOSPHOFRUCTOKINASE 1 FRUCTOSE 6- PHOSPHATE Phosphofructokinase 1 FRUCTOSE 1,6- BISPHOSPHATE

  32. REGULATION OF PHOSPHOFRUCTOKINASE 1 FRUCTOSE 6- PHOSPHATE Phosphofructokinase 2 Well fed state  Insulin cAMP protein kinase Starvation  Glucagon  cAMP  Protein kinase P Kinase Phosphatase FRUCTOSE 2,6- BISPHOSPHATE

  33. REGULATION OF PYRUVATE KINASE FRUCTOSE 1,6- BISPHOSPHATE + Pyruvate kinase PYRUVATE

  34. REGULATION OF PYRUVATE KINASE PHOSPHOENOLPYRUVATE Starvation  Glucose  Glucagon  cAMP  Protein kinase A P Pyruvate kinase GLUCONEOGENESIS PYRUVATE

  35. GLUCOSE 5-C sugars GLUCOSE 6 PHOSPHATE Glycerol-P 1, 3 BISPHOSPHOGLYCERATE TGs Fatty acids 2, 3 BPG Serine 3 PHOSPHOGLYCERATE Alanine PYRUVATE TCA cycle Glu & other amino acids ACETYL CoA GLYCOLYSIS AND OTHER METABOLIC PATHWAYS

  36. THANK YOU!

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