Glycolysis 2

• Glycolysis


  Degradation of glucose to pyruvate (Lactate under anaerobic) generating 7 ATP

  
• Professor Shivananda Nayak


  • Professor of Biochemistry
• Carbohydrate metabolism


  Glucose is degraded through glycolysis, citric acid cycle, gluconeogenesis, and glycogenesis

  
• Citric acid cycle


  The oxidation of acetyl CoA to CO2
• Gluconeogenesis


  The synthesis of glucose from non-carbohydrate precursors (amino acids, glycerol etc)

  
• Glycogenesis


  The synthesis of glycogen from glucose

  
• Glycogenolysis


  Breakdown of glycogen to glucose and then to lactate or pyruvate

  
• Hexose monophosphate shunt


  Alternative pathway to glycolysis and TCA cycle for the oxidation of glucose, directly oxidising glucose to CO2 and H2O

  
• Glycolysis (Embden Meyerhof pathway)

  • Carbohydrates are the important energy source of the body
  • Glucose is the preferred source of energy for most of the body tissues
  • Brain cells derive energy mainly from glucose
  • Pyruvate is the end product of aerobic glycolysis
  • Lactate is the end product of anaerobic glycolysis

  
• Importance of glycolysis


  • Takes place in all the cells of the body
  • Source of energy in erythrocytes
  • Anaerobic glycolysis forms the major source of energy for muscle during exercise
  • Provides carbon skeletons for the synthesis of non-essential amino acids
  • Most of the reactions of glycolysis are reversible
  • The entry of glucose from ECF to cell (ICF) is under the control of insulin
  • Glycolysis occurrence is the pre-requisite for the aerobic oxidation of carbohydrates
  • Aerobic oxidation takes place in the cells possessing mitochondria
  • Glycolysis is the major pathway for ATP synthesis in tissues lacking mitochondria (erythrocytes)

  
• Steps of Glycolysis


  1. Irreversible glucokinase/hexokinase reaction

  2. Reversible reaction

  3. Irreversible PFK reaction

  4. Reversible aldolase reaction splitting 6-carbon compound into two 3-carbon compounds

  5. Reversible glyceraldehyde 3-phosphate dehydrogenase reaction with high-energy bond

  6. Synthesis of 1 ATP from 1,3 bisphosphoglycerate

  7. Reversible reactions

  8. Reversible enolase reaction inhibited by fluoride

  9. Irreversible pyruvate kinase reaction trapping high energy of phosphoenolpyruvate into ATP

  
• Anaerobic glycolysis


  Pyruvate is converted to lactate to reoxidise NADH when oxygen is lacking

  
• Steps 5 and 10 of glycolysis are coupled

  
• Glycolysis is the major source of energy in anaerobiosis
• Formation of lactate allows the regeneration of NAD+ for glycolysis to proceed even in the absence of oxygen

  
• The occurrence of un-interrupted glycolysis is very important in skeletal muscle during strenuous exercise
• Brain, retina, renal medulla and GI tract derive their energy from glycolysis
• Glycolysis in the erythrocytes leads to lactate production

  
• Energetics of glycolysis


  • Energy consuming steps are hexokinase and phosphofructokinase reactions (-2 ATP)
  • Energy yielding steps are glyceraldehyde-3-phosphate dehydrogenase reaction (5 ATP from NADH) and substrate level phosphorylation (4 ATP)
  • Total ATP in aerobic glycolysis = 7 ATP/glucose
  • Anaerobic glycolysis produces 2 ATP/glucose

  
• Shuttle pathways


  Malate-aspartate shuttle produces 3 ATP, glycerol phosphate shuttle produces 2 ATP from cytosolic NADH
• Regulation of glycolysis


  • Insulin favours glycolysis by activating key enzymes
  • Glucose-6-phosphate inhibits hexokinase
  • PFK-1 is an inducible enzyme increased by insulin and decreased by glucagon
  • Pyruvate kinase is an inducible enzyme increased by insulin and decreased by glucagon

  
• Fructose 2,6-bisphosphate


  • Regulatory factor controlling PFK and glycolysis in the liver
  • Its synthesis and degradation is controlled by a bifunctional enzyme, regulated by cAMP-dependent phosphorylation

  
• Pasteur effect


  Inhibition of glycolysis by oxygen, due to inhibition of PFK by citrate and ATP

  
• Rapoport Luebering shunt


  • Bypasses the kinase reaction in erythrocytes, does not trap energy from 2,3-BPG
  • 2,3-BPG reduces the affinity of hemoglobin for oxygen, increasing oxygen unloading in tissues
  • Decreases in 2,3-BPG increase hemoglobin's affinity for oxygen

  
• Fate of pyruvate


  • Under aerobic conditions, pyruvate is transported into mitochondria and converted to acetyl-CoA by the pyruvate dehydrogenase complex
  • Lack of thiamine leads to pyruvate accumulation and conversion to lactate, causing lactic acidosis
  • Pyruvate dehydrogenase can be inhibited by arsenic and mercury

  
• Reference: Essentials of Biochemistry, Dr S Nayak