glucose metabolism and gluconeogenesis.pptx

in depth description of glycolysis

1. GLYCOLYSIS AND GLUCONEOGENESIS DR. CHIKONDE

2. Glycolysis (Embden-Meyerhof pathway) Glycolysis is the breakdown of glucose into pyruvate Anaerobic and aerobic glycolysis Only source of energy for erythrocytes Only pathway that occurs in all cells (cytosol) preliminary step before complete oxidation of glucose

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. 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

6. Step 1

7. Step 2 Product of step 1 is rearranged to the structural isomer fructose-6-phosphate by enzyme phosphoglucose isomerase - Converts an aldose to a ketose

8. Step 3 Substrate fructose-6-phosphate is phosphorylated by phosphofructokinase Product is fructose-1,6-bisphosphate Source of the phosphoryl group is ATP

9. 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

10. 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

11. 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

12. 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

13. Step 8 3-Phosphoglycerate is isomerized into 2-phosphoglycerate by the enzyme phosphoglycerate mutase Moves the phosphate group from carbon-3 to carbon-2

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

15. 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

16. Summary of glycolysis

17. 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

18. 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

19. 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

20. 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

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

22. 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

23. Comparison of Glycolysis and Gluconeogenesis

24. 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

25. 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

26. 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

27. 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

28. THANKS