Glycolysis and gluconeogenesis

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project on biochemistry by NITISH SHAH

Text of Glycolysis and gluconeogenesis


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. The two parts of glycolysis:Part one(enery invesment phase):glucose glucose 6-phosphatefructose 1,6- ATP diphosphate ATPPart two(energy generating phase):fructose 1,6- 2 pyruvic aciddiphosphate2 NADH 2 ATP 2 ATP 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 of2ATPs and 2NADHs 5. Glycolysis Coenzyme NAD+ is a biological oxidizingagent that converts C-H bonds to C-Obonds. In the process, NAD+ is reduced toNADH + H+. The phosphorylation of ADP requires energyand forms ATP, a high-energy nucleosidetriphosphate. The hydrolysis of ATP releases energy andforms ADP 6. Steps in glycolysis Step 1 Substrate glucose is phosphorylated byhexokinase Product is glucose-6-phosphate Source of the phosphoryl group is ATP Expenditure of ATP early in the pathway works asenergy debt necessary to get the pathway started 7. Step 1 8. Step 2 Product of step 1 is rearranged to thestructural isomer fructose-6-phosphate byenzyme phosphoglucose isomerase- Converts and aldose to a ketose 9. Step 3 Substrate fructose-6-phosphate isphosphorylated by phosphofructokinase Product is fructose-1,6-bisphosphate Source of the phosphoryl group is ATP 10. Step 4 Product of step 3 is split into two 3-carbonintermediates by the enzyme aldolaseforming: Glyceraldehyde-3-phosphate (substrate of next reaction) Dihydroxyacetone phosphate 11. Step 5 Dihydroxyacetone phosphate is rearrangedinto a second glyceraldehyde-3-phosphate bythe enzyme triose phosphate isomerase Glyceraldehyde-3-phosphate is the only substratefor the next reaction 12. Step 6 Substrate glyceraldehyde-3-phosphate isoxidized 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. Step 7 Harvest energy in the form of ATP 1,3-Bisphosphoglycerate high energyphosphate group is transferred to ADP byphosphoglycerate kinase: 3-Phosphoglycerate ATP This is the first substrate level phosphorylationof glycolysis 14. Step 8 3-Phosphoglycerate is isomerized into 2-phosphoglycerate by the enzymephosphoglycerate mutase Moves the phosphate group from carbon-3 to carbon-2 15. Step 9 The enzyme enolase catalyzes dehydration of2-phospholgycerate Phosphoenolpyruvate Energy rich highest energy phosphorylated compound in metabolism 16. Step 10 Final substrate-level dehydration in thepathway Phosphoenolpyruvate serves as donor of thephosphoryl group transferred to ADP bypyruvate kinase making ATP and releasingwater Pyruvate is the final product of glycolysis 17. Summary of glycolysis 18. Net result of glycolysis The final products are: Two pyruvic acid molecules Two NADH + H+ molecules (reducedNAD+) A net gain of two ATP molecules 19. Glycolysis and other hexoses Fructose is obtained by the hydrolysis of thedisaccharide sucrose, found in sugar beetsand sugarcane Galactose is obtained by the hydrolysis of thedissacharide lactose in milk Mannose is obtained from polysaccharides infruits such as cranberries and currants 20. Fate of pyruvateAcetyl CoA, CHCOSCoA, is formed underaerobic conditionsLactate, CHCH(OH)CO2, is formed underanaerobic conditions.Ethanol CHCH2OH, is formed in fermentation 21. Gluconeogenesis: The Synthesis of Glucose Gluconeogenesis makes glucosefrom noncarbohydrate startingmaterials Lactate Glycerol Most amino acids (not leucine, lysine) Glycerol and amino acids are used onlyin starvation conditions Process occurs primarily in the liver 22. The gluconeogenic pathway converts pyruvate into glucose. gluconeogenesispyruvate glucose glycolysisGluconeogenesis is not a reversal of glycolysis 23. Comparison of Glycolysisand Gluconeogenesis While basically opposite processesglycolysis and gluconeogenesis are not asimple reversal of each other The three nonreversible steps of glycolysismust be bypassed with new routes Pyruvate Phosphoenolpyruvate Fructose-1,6-bisphosphate Fructose-6-phosphate Glucose-6-phosphate Glucose 24. Comparison of Glycolysis and Gluconeogenesis 25. Pyruvate Phosphoenolpyruvate The two enzymes that catalyze the reactions forbypass of the Pyruvate Kinase reaction are thefollowing:Pyruvate Carboxylase (Gluconeogenesis) catalyzes: pyruvate + HCO3 + ATP oxaloacetate + ADP + Pi PEP Carboxykinase (Gluconeogenesis) catalyzes: oxaloacetate + GTP PEP + GDP + CO2 Pyruvate Carboxylase PEP CarboxykinaseO OC O O O O C ATP ADP + Pi C O GTP GDPC C OCH 2 C OPO32 HCO3 C CO 2 CH 3CH 2O O pyruvateoxaloacetatePEP 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. Glucose-6-phosphate Glucose Glucose is formed by the hydrolysis ofgulcose 6-phosphate in a reactioncatalyzed by gulcose 6-phosphateGulose 6-phosphate + H2O gulcose + Pi 28. glyceraldehyde-3-phosphateNAD+ + PiGlyceraldehyde-3-phosphate NADH + H+ Dehydrogenase1,3-bisphosphoglycerate ADPSummary ofPhosphoglycerate Kinase ATPGluconeogenesis 3-phosphoglycerate Pathway:Phosphoglycerate MutaseGluconeogenesis2-phosphoglycerateenzyme names in H2OEnolasered. phosphoenolpyruvateGlycolysis enzyme CO2 + GDPnames in blue.PEP Carboxykinase GTPoxaloacetate Pi + ADPPyruvate CarboxylaseHCO3 + ATP pyruvateGluconeogenesis 29. glucoseGluconeogenesisPi Glucose-6-phosphatase H2Oglucose-6-phosphate Phosphoglucose Isomerasefructose-6-phosphatePiFructose-1,6-bisphosphatase H2Ofructose-1,6-bisphosphate Aldolaseglyceraldehyde-3-phosphate + dihydroxyacetone-phosphate Triosephosphate Isomerase (continued) 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. Reciprocal regulation ofgluconeogenesis and glycolysis inthe liver. The interconversion offructose 6-phosphate and fructose 1,6- bisphosphate is stringently controlled The interconversion of phosphoenolpyruvateand pyruvate also isprecisely regulated. 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. THANKS


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