Glycolysis and gluconeogenesis

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1. GLYCOLYSIS AND GLUCONEOGENESIS INSTRUCTOR-RCL GROUP 4 NITI KR. SHAH ANUP BIK. SHAH REVOLUTION SHERETHA SMIRITI KHADKA BIJAY RAJBANSHI TAKAR ABDIGANI

2. Glycolysis ( Embden -Meyerhof pathway) 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 : glucose glucose 6-phosphate fructose 1,6- diphosphate Part one( enery invesment phase) : ATP ATP Part two(energy generating phase) : fructose 1,6- diphosphate 2 ATP 2 ATP 2 NADH 2 pyruvic acid

4. Glycolysis Overall net equation is: Glucose + 2NAD + 2ADP + 2P i  2 pyruvates + 2NADH + 2 ATP + 2 NADH + 2 H + + 2 H 2 O Glycolysis is exergonic - produces net of 2ATPs and 2NADHs

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. 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. Step 1

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. Step 3 Substrate fructose-6-phosphate is phosphorylated 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-carbon intermediates by the enzyme aldolase forming: Glyceraldehyde-3-phosphate (substrate of next reaction) Dihydroxyacetone phosphate

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. 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. 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. 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. Step 9 The enzyme enolase catalyzes dehydration of 2-phospholgycerate Phosphoenolpyruvate Energy rich – highest energy phosphorylated compound in metabolism

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. Summary of glycolysis

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. 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 Glycolysis and other hexoses

20. Acetyl CoA , CH₃COSCoA , is formed under aerobic conditions Lactate, CH₃CH(OH)CO2⁻, is formed under anaerobic conditions. Ethanol CH₃CH 2 OH, is formed in fermentation Fate of pyruvate

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. The gluconeogenic pathway converts pyruvate into glucose. pyruvate glucose → → → → → gluconeogenesis glycolysis Gluconeogenesis is not a reversal of glycolysis

23. Comparison of Glycolysis and 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. Comparison of Glycolysis and Gluconeogenesis

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 + HCO 3 - + ATP  oxaloacetate + ADP + P i PEP Carboxykinase ( Gluconeogenesis ) catalyzes: oxaloacetate + GTP  PEP + GDP + CO 2

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 + H 2 O  fructose 6-phosphate + P i

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 + H 2 O  gulcose + P i

28. Summary of Gluconeogenesis Pathway: Gluconeogenesis enzyme names in red. Glycolysis enzyme names in blue.

29. Gluconeogenesis Regulation Step 3 of glycolysis : Catalyzed by phosphofructokinase Stimulated by: high AMP, ADP, P i Inhibited by: high ATP Reverse occurs in gluconeogenesis : Fructose-1,6-bisphosphatase s timulated by high ATP At times of excess energy (high ATP) gluconeogenesis is favored

30. Reciprocal regulation of gluconeogenesis 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.

31. 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

32. THANKS