Glycolysis and gluconeogenesis


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project on biochemistry by NITISH SHAH

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Glycolysis and gluconeogenesis

  2. 2. Glycolysis (Embden-Meyerhofpathway) • Glycolysis is the breakdown of glucose into pyruvic acid • Does not require oxygen • Occurs free in the cytoplasm • Begins with D-glucose as the substrate
  3. 3. The two parts of glycolysis:Part one(enery invesment phase):glucose glucose 6-phosphate fructose 1,6- ATP diphosphate ATPPart two(energy generating phase):fructose 1,6- 2 pyruvic aciddiphosphate 2 NADH 2 ATP 2 ATP
  4. 4. Glycolysis• Overall net equation is:Glucose + 2NAD + 2ADP + 2Pi 2 pyruvates + 2NADH + 2 ATP + 2 NADH + 2 H+ + 2 H2O• Glycolysis is exergonic - produces net of 2ATPs and 2NADHs
  5. 5. Glycolysis• Coenzyme NAD+ is a biological oxidizing agent that converts C-H bonds to C-O bonds. In the process, NAD+ is reduced to NADH + H+.• The phosphorylation of ADP requires energy and forms ATP, a high-energy nucleoside triphosphate.• The hydrolysis of ATP releases energy and forms ADP
  6. 6. Steps in glycolysis• Step 1• Substrate glucose is phosphorylated by hexokinase• Product is glucose-6-phosphate – Source of the phosphoryl group is ATP – Expenditure of ATP early in the pathway works as energy “debt” necessary to get the pathway started
  7. 7. Step 1
  8. 8. Step 2• Product of step 1 is rearranged to the structural isomer fructose-6-phosphate by enzyme phosphoglucose isomerase - Converts and aldose to a ketose
  9. 9. Step 3• Substrate fructose-6-phosphate is phosphorylated by phosphofructokinase• Product is fructose-1,6-bisphosphate – Source of the phosphoryl group is ATP•
  10. 10. Step 4• Product of step 3 is split into two 3-carbon intermediates by the enzyme aldolase forming: – Glyceraldehyde-3-phosphate (substrate of next reaction) – Dihydroxyacetone phosphate
  11. 11. Step 5• Dihydroxyacetone phosphate is rearranged into a second glyceraldehyde-3-phosphate by the enzyme triose phosphate isomerase – Glyceraldehyde-3-phosphate is the only substrate for the next reaction
  12. 12. Step 6• Substrate glyceraldehyde-3-phosphate is oxidized to a carboxylic acid by glyceraldehyde- 3-phosphate dehydrogenase – Reduces NAD+ to NADH• Product is 1,3-Bisphosphoglycerate – New phosphate group attached with a “high-energy” bond
  13. 13. Step 7• Harvest energy in the form of ATP• 1,3-Bisphosphoglycerate high energy phosphate group is transferred to ADP by phosphoglycerate kinase: – 3-Phosphoglycerate – ATP• This is the first substrate level phosphorylation of glycolysis
  14. 14. Step 8• 3-Phosphoglycerate is isomerized into 2- phosphoglycerate by the enzyme phosphoglycerate mutase – Moves the phosphate group from carbon-3 to carbon-2
  15. 15. Step 9• The enzyme enolase catalyzes dehydration of 2-phospholgycerate – Phosphoenolpyruvate • Energy rich – highest energy phosphorylated compound in metabolism
  16. 16. Step 10• Final substrate-level dehydration in the pathway• Phosphoenolpyruvate serves as donor of the phosphoryl group transferred to ADP by pyruvate kinase making ATP and releasing water – Pyruvate is the final product of glycolysis
  17. 17. Summary of glycolysis
  18. 18. Net result of glycolysis• The final products are: – Two pyruvic acid molecules – Two NADH + H+ molecules (reduced NAD+) – A net gain of two ATP molecules
  19. 19. Glycolysis and other hexoses• Fructose is obtained by the hydrolysis of the disaccharide sucrose, found in sugar beets and sugarcane• Galactose is obtained by the hydrolysis of the dissacharide lactose in milk• Mannose is obtained from polysaccharides in fruits such as cranberries and currants
  20. 20. Fate of pyruvateAcetyl CoA, CH₃COSCoA, is formed under aerobic conditionsLactate, CH₃CH(OH)CO2⁻, is formed under anaerobic conditions.Ethanol CH₃CH2OH, is formed in fermentation
  21. 21. Gluconeogenesis: The Synthesis of Glucose• Gluconeogenesis makes glucose from noncarbohydrate starting materials – Lactate – Glycerol – Most amino acids (not leucine, lysine) – Glycerol and amino acids are used only in starvation conditions• Process occurs primarily in the liver
  22. 22. The gluconeogenic pathway converts pyruvate into glucose. gluconeogenesispyruvate → → → → → glucose glycolysisGluconeogenesis is not a reversal of glycolysis
  23. 23. Comparison of Glycolysisand Gluconeogenesis• While basically opposite processes glycolysis and gluconeogenesis are not a simple reversal of each other• The three nonreversible steps of glycolysis must be bypassed with new routes – Pyruvate  Phosphoenolpyruvate – Fructose-1,6-bisphosphate  Fructose-6- phosphate – Glucose-6-phosphate  Glucose
  24. 24. Comparison of Glycolysis and Gluconeogenesis
  25. 25. Pyruvate  Phosphoenolpyruvate •The two enzymes that catalyze the reactions for bypass of the Pyruvate Kinase reaction are the following:•Pyruvate Carboxylase (Gluconeogenesis) catalyzes: pyruvate + HCO3 + ATP  oxaloacetate + ADP + Pi •PEP Carboxykinase (Gluconeogenesis) catalyzes: oxaloacetate + GTP  PEP + GDP + CO2 Pyruvate Carboxylase PEP Carboxykinase O O C O O O O C ATP ADP + Pi C O GTP GDP C C O CH 2 C OPO32 HCO3 C CO 2 CH 3 CH 2 O O pyruvate oxaloacetate PEP
  26. 26. Fructose-1,6-bisphosphate  Fructose-6-phosphate• Fructose 6-phosphate is formed from 1,6- bisphosphate by hydrolysis of the phosphate ester at carbon1.Fructose 1,6- bisphosphatase catalyzes this exergonic hydrolysis Fructose 1,6-bisphosphate + H2O  fructose 6-phosphate + Pi
  27. 27. Glucose-6-phosphate  Glucose• Glucose is formed by the hydrolysis of gulcose 6-phosphate in a reaction catalyzed by gulcose 6-phosphate Gulose 6-phosphate + H2O  gulcose + Pi
  28. 28. glyceraldehyde-3-phosphate NAD+ + Pi Glyceraldehyde-3-phosphate NADH + H+ Dehydrogenase 1,3-bisphosphoglycerate ADP Summary of Phosphoglycerate Kinase ATPGluconeogenesis 3-phosphoglycerate Pathway: Phosphoglycerate MutaseGluconeogenesis 2-phosphoglycerateenzyme names in H2O Enolase red. phosphoenolpyruvateGlycolysis enzyme CO2 + GDP names in blue. PEP Carboxykinase GTP oxaloacetate Pi + ADP Pyruvate Carboxylase HCO3 + ATP pyruvate Gluconeogenesis
  29. 29. glucose Gluconeogenesis Pi Glucose-6-phosphatase H2O glucose-6-phosphate Phosphoglucose Isomerase fructose-6-phosphate Pi Fructose-1,6-bisphosphatase H2O fructose-1,6-bisphosphate Aldolaseglyceraldehyde-3-phosphate + dihydroxyacetone-phosphate Triosephosphate Isomerase (continued)
  30. 30. Gluconeogenesis Regulation• Step 3 of glycolysis: – Catalyzed by phosphofructokinase – Stimulated by: high AMP, ADP, Pi – Inhibited by: high ATP• Reverse occurs in gluconeogenesis: – Fructose-1,6-bisphosphatase stimulated by high ATP – At times of excess energy (high ATP) gluconeogenesis is favored
  31. 31. Reciprocal regulation ofgluconeogenesis and glycolysis in the liver. The interconversion of fructose 6-phosphate and fructose 1,6- bisphosphate is stringently controlled The interconversion of phosphoenolpyruvate and pyruvate also is precisely regulated.
  32. 32. Cori Cycle• In the Cori cycle, – Lactate from skeletal muscle is transferred to the liver – Converted to pyruvate then glucose – This glucose can be returned to the muscle
  33. 33. THANKS