Glycolysis- Reactions, Regulation and application.pptx

Glycolysis- features, reactions, phases, steps, diagrams, fate of pyruvate, regulation and applications

1. GLYCOLYSIS

2. INTRODUCTION Glycolysis is the first step in the breakdown of glucose to extract energy for cellular metabolism. Nearly all living organisms carry out glycolysis as part of their metabolism Glycolysis is derived from the Greek words (glycose—sweet or sugar; lysis—dissolution). The complete pathway of glycolysis was elucidated in 1940.

3. This pathway is often referred to as Embden -Meyerhof pathway (E.M. Pathway) in honour of the two biochemists who made a major contribution to the knowledge of glycolysis.
Glycolysis is defined as the sequence of reactions converting glucose (or glycogen) to pyruvate or lactate, with the production of ATP..

4. SALIENT FEATURES 1. Glycolysis takes place in all cells of the body. The enzymes of this pathway are present in the cytosomal fraction of the cell. 2. Glycolysis occurs in the absence of oxygen (anaerobic) or in the presence of oxygen (aerobic). Lactate is the end product under anaerobic condition. In the aerobic condition, pyruvate is formed, which is then oxidized to CO2 and H2O. 3. Glycolysis is a major pathway for ATP synthesis in tissues lacking mitochondria, e.g. erythrocytes, cornea, lens etc.

5. 4. Glycolysis is very essential for brain which is dependent on glucose for energy. The glucose in brain has to undergo glycolysis before it is oxidized to CO2 and H2O. 5. Glycolysis (anaerobic) may be summarized by the net reaction Glucose + 2ADP + 2Pi o 2Lactate + 2ATP 6. Glycolysis is a central metabolic pathway with many of its intermediates providing branch point to other pathways. Thus, the intermediates of glycolysis are useful for the synthesis of amino acids and fat. 7. Reversal of glycolysis along with the alternate arrangements at the irreversible steps, will result in the synthesis of glucose (gluconeogenesis).

6. REACTIONS OF GLYCOLYSIS The pathway can be divid ded into three distinct phases A. Energy investment phase or priming stage B. Splitting phase C. Energy generation phase.

7. A. ENERGY INVESTMENT PHASE Step 1. A phosphate group is transferred from ATP to glucose, making glucose-6-phosphate. Glucose-6-phosphate is more reactive than glucose, and the addition of the phosphate also traps glucose inside the cell since glucose with a phosphate can’t readily cross the membrane. Step 2. Glucose-6-phosphate is converted into its isomer, fructose-6-phosphate. Step 3. A phosphate group is transferred from ATP to fructose-6-phosphate, producing fructose-1,6-bisphosphate. This step is catalyzed by the enzyme phosphofructokinase, which can be regulated to speed up or slow down the glycolysis pathway.

8. B. SPLITTING PHASE Step 4. Fructose-1,6-bisphosphate splits to form two three-carbon sugars: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate. They are isomers of each other, but only one—glyceraldehyde-3-phosphate—can directly continue through the next steps of glycolysis. Step 5. DHAP is converted into glyceraldehyde-3-phosphate. The two molecules exist in equilibrium, but the equilibrium is “pulled” strongly downward, in the scheme of the diagram above, as glyceraldehyde-3-phosphate is used up. Thus, all of the DHAP is eventually converted.

9. C. ENERGY GENERATION PHASE Step 6. Two half reactions occur simultaneously: 1) Glyceraldehyde-3-phosphate (one of the three-carbon sugars formed in the initial phase) is oxidized, and 2)NAD + is reduced to NADH and H + and . The overall reaction is exergonic, releasing energy that is then used to phosphorylate the molecule, forming 1,3-bisphosphoglycerate. Step 7. 1,3-bisphosphoglycerate donates one of its phosphate groups to ADP, making a molecule of ATP and turning into 3-phosphoglycerate in the process

10. Step 8. 3-phosphoglycerate is converted into its isomer, 2-phosphoglycerate. Step 9. 2-phosphoglycerate loses a molecule of water, becoming phosphoenolpyruvate (PEP). PEP Is an unstable molecule, poised to lose its phosphate group in the final step of glycolysis. Step 10. PEP readily donates its phosphate group to ADP, making a second molecule of ATP. As it loses its phosphate, PEP is converted to pyruvate, the end product of glycolysis.

11. FATE OF PYRUVATE After glycolysis, the fate of pyruvate depends on the availability of oxygen and the metabolic needs of the cell: 1.Aerobic Respiration: In the presence of oxygen, pyruvate enters the mitochondria where it undergoes oxidative decarboxylation to form acetyl-CoA. Acetyl-CoA then enters the citric acid cycle (Krebs cycle) to generate ATP through oxidative phosphorylation.

12. 2.Anaerobic Respiration (Fermentation): In the absence of oxygen, pyruvate can undergo fermentation to regenerate NAD+ for glycolysis to continue. In humans, pyruvate is converted into lactate (lactic acid fermentation) or ethanol and carbon dioxide (alcoholic fermentation) depending on the organism and cell type. 3.Gluconeogenesis: Pyruvate can also be converted back into glucose via gluconeogenesis, particularly in the liver and kidneys. This process is important for maintaining blood glucose levels during fasting or prolonged exercise.

13. 4.Gluconeogenesis: Pyruvate can also be converted back into glucose via gluconeogenesis, particularly in the liver and kidneys. This process is important for maintaining blood glucose levels during fasting or prolonged exercise. 5.Lipogenesis: Under certain conditions, pyruvate can be converted into acetyl-CoA and then used as a precursor for fatty acid synthesis ( lipogenesis ), contributing to the formation of triglycerides and other lipids.

14. REGULATION OF GLYCOLYSIS Glycolysis Is tightly regulated to maintain cellular energy homeostasis. Here are some key regulatory mechanisms: 1.Hexokinase: Hexokinase catalyzes the conversion of glucose to glucose-6-phosphate, the first step of glycolysis.
It is inhibited by its product, glucose-6-phosphate, through feedback inhibition. This helps prevent excessive glucose uptake and glycolysis when cellular energy needs are met.

15. 2.Phosphofructokinase-1 (PFK-1): PFK-1 catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, a key regulatory step in glycolysis.
PFK-1 is allosterically activated by AMP and fructose-2,6-bisphosphate (F2,6-BP), and inhibited by ATP and citrate.
F2,6-BP is synthesized by phosphofructokinase-2 (PFK-2), which is activated by insulin and inhibited by glucagon. Therefore, hormones like insulin promote glycolysis by increasing the levels of F2,6-BP.

16. 3.Pyruvate Kinase: Pyruvate kinase catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate, the last step of glycolysis.
It is allosterically activated by fructose-1,6-bisphosphate (F1,6-BP), an intermediate of glycolysis.
Pyruvate kinase can also be regulated by reversible phosphorylation, with phosphorylation inhibiting its activity.

17. 4.Regulation by Hormones: Insulin promotes glycolysis by increasing the cellular uptake of glucose and activating enzymes like PFK-2, leading to the synthesis of F2,6-BP and activation of PFK-1.
Glucagon and epinephrine, on the other hand, inhibit glycolysis by promoting the breakdown of glycogen stores and activating pathways like gluconeogenesis.

18. 5.Feedback Inhibition: High levels of ATP and citrate inhibit PFK-1, the rate-limiting enzyme of glycolysis, to prevent excessive ATP production when energy needs are met.
Additionally, high levels of ATP and acetyl-CoA inhibit pyruvate kinase, slowing down glycolysis and promoting alternative pathways like gluconeogenesis or fatty acid synthesis. These regulatory mechanisms ensure that glycolysis is finely tuned to match cellular energy demands and metabolic conditions.

19. APPLICATIONS OF GLYCOLYSIS Glycolysis has various applications across different fields: 1.Biotechnology and Biomedical Research: Glycolysis is a fundamental process in cellular metabolism, making it crucial for studying cellular physiology and disease mechanisms.
Understanding glycolysis helps in developing therapies for metabolic disorders such as diabetes and cancer, where dysregulation of glycolytic pathways is common.

20. 2.Food and Beverage Industry: Glycolysis is involved in fermentation processes used to produce various food and beverage products.
Yeast fermentation, which relies on glycolysis, is used to produce bread, beer, wine, and other fermented foods. 3.Biomedical Imaging: Positron emission tomography (PET) scans utilize radiolabeled glucose analogs to visualize metabolic activity in tissues.
The uptake of these analogs by cells and subsequent metabolism through glycolysis allow for the detection and monitoring of diseases such as cancer.

21. 4.Biofuel Production: Glycolysis serves as a basis for the production of biofuels from renewable resources.
Microorganisms can be engineered to metabolize sugars through glycolysis to produce bioethanol or other biofuels as alternatives to fossil fuels. 5. Industrial Biotechnology: Glycolysis is utilized in the production of various biochemicals and pharmaceuticals.
Metabolic engineering approaches can enhance glycolytic pathways in microbial hosts to increase the production of valuable compounds such as amino acids, organic acids, and bio-based chemicals.

22. 5.Environmental Remediation: Some microorganisms can metabolize pollutants through glycolytic pathways, contributing to bioremediation efforts.
Harnessing glycolysis in microbial communities can aid in the cleanup of environmental contaminants, such as hydrocarbons and organic pollutants. Overall, the applications of glycolysis span multiple disciplines, from basic research to industrial processes, demonstrating its importance in various fields of science and technology.

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