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GLYCOLYSIS

GLYCOLYSIS. EMP PATHWAY (EMBEDEN-MEYERHOF PATHWAY ). Introduction. Glycolysis is derived from greek word Glycose -sweet/sugar Lysis - dissolution

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GLYCOLYSIS

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  1. GLYCOLYSIS EMP PATHWAY (EMBEDEN-MEYERHOF PATHWAY)

  2. Introduction • Glycolysis is derived from greek word Glycose-sweet/sugar Lysis- dissolution Def : It is the sequence of reactions converting glucose(or glycogen) to pyruvate or lactate with the production of ATP(oxidation of glucose to pyruvate &lactate). • Glycolysis is the metabolic process that serves as the foundation for both aerobic and anaerobic cellular respiration. In glycolysis, glucose is converted into pyruvate. Glucose is a six- memebered ring molecule found in the blood and is usually a result of the breakdown of carbohydrates into sugars. It enters cells through specific transporter proteins that move it from outside the cell into the cell’s cytosol. All of the glycolytic enzymes are found in the cytosol. • The overall reaction of glycolysis which occurs in the cytoplasm is represented simply as: • C6H12O6 + 2 NAD+ + 2 ADP + 2 P —–> 2 pyruvic acid, (CH3(C=O)COOH + 2 ATP + 2 NADH + 2 H+

  3. Features • It takes place in all the cells of the body. • Glycolysis occurs in the absence of oxygen(anaerobic-lactate) or in presence of oxygen(aerobic-pyruvate). • It is a major pathway for ATP synthesis in tissues lacking mitochondria(erythrocytes,cornea,lens),it provides energy to the tissues. • It is very essential for brain which is dependent on glucose for energy. • It is a central metabolic pathway that provides branch point to other pathways(synthesis of amino acids& fats) • Reversal of glycolysis will result in the synthesis of glucose(gluconeogenesis)

  4. GLYCOLYSIS PATHWAYThe sequence of reactions: 1. Energy investment phase(1-3 STEPS) 2. Splitting phase (4&5 STEPS) 3. Energy generation phase(6-10 STEPS)

  5. Step 1: Hexokinase The first step in glycolysis is the conversion(Phosphorylation) of D-glucose into glucose-6-phosphate. The enzyme that catalyzes this reaction is hexokinase ,this is an irreversible reaction dependent on magnesium and ATP.

  6. Step 2: PhosphoglucoseIsomerase The second reaction of glycolysis is the rearrangement(isomerization) of glucose 6-phosphate (G6P) into fructose 6-phosphate (F6P) by glucose phosphate isomerase (PhosphoglucoseIsomerase/phosphohexoseisomerase)

  7. Step 3: Phosphofructokinase(PFK) Phosphofructokinase, with magnesium as a cofactor, changes(phosphorylate) fructose 6-phosphate into fructose 1,6-bisphosphate This is an irreversible and regulatory step in glycolysis.

  8. Step 4: Aldolase The enzyme Aldolase(fructose 1,6,bisphosphatealdolase) splits fructose 1, 6-bisphosphate into two sugars that are isomers of each other. These two sugars are dihydroxyacetone phosphate  (DHAP) and glyceraldehyde 3-phosphate (GAP).

  9. Step 5: Triphosphateisomerase/phosphotrioseisomerase The enzyme triophosphateisomerase rapidly inter- converts the molecules dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP). Glyceraldehyde phosphate is removed / used in next step of Glycolysis

  10. Step 6: Glyceraldehyde-3-phosphate Dehydrogenase Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) dehydrogenates and adds an inorganic phosphate to glyceraldehyde 3-phosphate, producing 1,3-bisphosphoglycerate This is an imp step involves the formation of NADH+H. Iodoacetate and arsenate inhibits the enzyme GAPDH. In aerobic condition NADH Passethroough ETC and 6 ATP are synthesized by oxidative phosphorylation.

  11. Step 7: PhosphoglycerateKinase Phosphoglyceratekinase transfers a phosphate group from 1,3-bisphosphoglycerate to ADP to form ATP and 3-phosphoglycerate It is a good example of substrate level phosphorylation. since ATP is synthesized by the substrate with out the involvement of ETC.

  12. Step 8: PhosphoglycerateMutase The enzyme phosphoglyceromutase relocates(isomerization) the P from 3- phosphoglycerate from the 3rd carbon to the 2nd carbon to form 2-phosphoglycerate.

  13. Step 9: Enolase • The enzyme enolase removes a molecule of water from 2-phosphoglycerate to form phosphoenolpyruvic acid (PEP) • This enzyme requires Mg2+& Mn2+ & is inhibited by flouride. • For blood glucose estimation flouride is added to the blood to prevent glycolysis by the cells so that it can be correctly estimated.

  14. Step 10: PyruvateKinase The enzyme pyruvatekinase transfers a P from phosphoenolpyruvate (PEP) to ADP to form pyruvic acid and ATP (substrate level phosphorylation) Pyruvatekinase requires K+& either Mg2+ or Mn2+. In anaerobic conditions (in absence of oxygen)due to limited amount of coenzyme NAD in the cells the NADH must be reoxidised to NAD to continue the glycolyticcycle,this is achieved by the enzyme lactate dehydrogenaase (LDH) which reoxidises NADH TO NAD with out producing ATP. • Glycolysis in erythrocytes leads to lactate production. • Brain, retina ,skin,renalmedulla ,GIT derive most of their energy from glycolysis.

  15. Under Anaerobic Conditions – 2 ATP are synthesized. • Under Aerobic Conditions- 8 Or 6 ATP Are Synthesized. REGULATION OF GLYCOLYSIS 3 types of mechanisms are involved in the regulation of glycolysis : Induction and repression of key enzymes(glucose,insulin) Covalent modification by reversible phosphorylationtion Allosteric modification. • The 3 enzymes- • Hexokinase(or glucokinase) • Phosphofructokinase • Pyruvatekinase • catalyse the irreversible reactions and regulate the glycolysis.

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