1 / 23

Glycolysis & the Oxidation of Pyruvate

Glycolysis & the Oxidation of Pyruvate. Biomedical Importance. Definition of Glycolysis : The major pathway for glucose metabolism ,occurs in the cytosol of all cells. Anaerobic Glycolysis : Occurs in Erythrocytes,because they lack mitochondria.

toniar
Download Presentation

Glycolysis & the Oxidation of Pyruvate

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Glycolysis & the Oxidation of Pyruvate

  2. Biomedical Importance • Definition of Glycolysis: The major pathway for glucose metabolism ,occurs in the cytosol of all cells. Anaerobic Glycolysis : Occurs in Erythrocytes,because they lack mitochondria. Aerobic Glycolysis : When glucose is oxidized beyond pyruvate,which requires;Oxygen,mitochondrial enzyme systems,the respiratory chain and the citric acid cycle.

  3. Glycolysis can function under Anaerobic conditions: When a muscle contracts in an anaerobic medium (no oxygen) the product is Lactate,and glycogen disapears. When oxygen is admitted,Lactate disapears.

  4. The Reactions of Glycolysis • Glycolysis occurs in the cytosol. • The overall equation to lactate is: Glucose + 2ADP + 2Pi→ 2Lactate +2ATP+2H2O

  5. Glycolysis takes place in the cytosol of cells. Glucose enters the Glycolysis pathway by conversion to glucose-6-phosphate. Initially there is energy input corresponding to cleavage of two ~P bonds of ATP.

  6. 1. Hexokinase catalyzes: Glucose + ATPglucose-6-P + ADP The reaction involves nucleophilic attack of the C6 hydroxyl O of glucose on P of the terminal phosphate of ATP. ATP binds to the enzyme as a complex with Mg++.

  7. 2. Phosphoglucose Isomerasecatalyzes: glucose-6-P (aldose) fructose-6-P (ketose) The mechanism involves acid/base catalysis, with ring opening, isomerization via an enediolate intermediate, and then ring closure. A similar reaction catalyzed by Triosephosphate Isomerase will be presented in detail.

  8. 3. Phosphofructokinase catalyzes: fructose-6-P + ATP fructose-1,6-bisP + ADP This highly spontaneous reaction has a mechanism similar to that of Hexokinase. The Phosphofructokinase reaction is the rate-limiting step of Glycolysis. The enzyme is highly regulated, as will be discussed later.

  9. 4. Aldolase catalyzes: fructose-1,6-bisphosphate  dihydroxyacetone-P + glyceraldehyde-3-P The reaction is an aldol cleavage, the reverse of an aldol condensation. Note that C atoms are renumbered in products of Aldolase.

  10. 5. Triose Phosphate Isomerase(TIM) catalyzes: dihydroxyacetone-P glyceraldehyde-3-P Glycolysis continues from glyceraldehyde-3-P. TIM's Keq favors dihydroxyacetone-P. Removal of glyceraldehyde-3-P by a subsequent spontaneous reaction allows throughput.

  11. 6. Glyceraldehyde-3-phosphate Dehydrogenase catalyzes: glyceraldehyde-3-P + NAD+ + Pi 1,3-bisphosphoglycerate + NADH + H+

  12. 7. Phosphoglycerate Kinase catalyzes: 1,3-bisphosphoglycerate + ADP  3-phosphoglycerate +ATP This phosphate transfer is reversible (low DG), since one ~P bond is cleaved & another synthesized. The enzyme undergoes substrate-induced conformational change similar to that of Hexokinase.

  13. 8. Phosphoglycerate Mutase catalyzes: 3-phosphoglycerate2-phosphoglycerate Phosphate is shifted from the OH on C3 to the OH on C2.

  14. 9. Enolase catalyzes 2-phosphoglyceratephosphoenolpyruvate+H2O This Mg++-dependent dehydration reaction is inhibited by fluoride. Fluorophosphate forms a complex with Mg++ at the active site.

  15. 10. Pyruvate Kinase catalyzes: phosphoenolpyruvate + ADPpyruvate+ATP

  16. At this point the redox state of the tissue determines the fate of pyruvate: 1-Under anaerobic conditions,the NADH produced cannot be oxidized on the respiratory chain,Therefor its oxidized by the reduction of Pyruvate to lactate. 2-Under aerobic conditions Pyruvate is taken into mitochondria and is converted to AcetylCoA which is oxidized in citric acid cycle.The NADH produced in glycolysis are taken into mitochondria by a shuttle and reoxidized.

  17. Glycolysis Balance sheet for ~P bonds of ATP: • How many ATP ~P bonds expended? ________ • How many ~P bonds of ATP produced? (Remember there are two 3C fragments from glucose.) ____4____ • Net production of ~P bonds of ATP per glucose: ___2_____ 2 4 2

  18. Tissues that function under hypoxic circumstances tend to produce Lactate

  19. Glycolysis is regulated at 3 steps involving nonequilibrium reactions • Three reactions of Glycolysis are irreversible These reactions are catalyzed by: -Hexokinase -Phosphofructokinase -Pyruvate Kinase Cells which have enzymes specific for reversing these reactions are capable of Gluconeogenesis.

  20. Glycolysis continued. Recall that there are 2 GAP per glucose.

  21. The Oxidation of Pyruvate to Acetyl-CoA is the irreversible route from Glycolysis→Citric acid cycle 1-Pyruvate is transported into mitochondria. 2-Pyruvate is oxidized to Acetyl-CoA by Pyruvate dehydrogenase complex. Pyruvate + NAD + CoA → Acetyl-CoA+NADH+H+CO2 In Thiamin deficiency Glucose metabolism is impaired ,and there is significant (life threatening) Lactic Acidoses.(?)

  22. Oxidation of Glucose yields up to 32 ATP under Aerobic conditions but only 2 when O2 is absent

More Related