Glycolysis Cycle (Embden–Meyerhof–Parnas EMP Pathway) : Definition, Steps, Process, Diagram, Products, Energetics, Regulation, Summary
- The breakdown of glucose to pyruvic acid is called glycolysis.
- Under aerobic condition, pyruvic acid enters mitochondria and is completely oxidized to CO2 and H2O. Whereas, under anaerobic conditions, pyruvate is converted to lactic acid.
- Site of reactions : All the reaction steps take place in the cytoplasm.
Steps of EMP Pathway
Glucose is converted to pyruvate in 10 steps by glycolysis.
EMP Pathway is an extramitochondrial pathway and is carried by a group of eleven enzymes.
- Mutases are enzymes which catalyze the transposition of functional groups.
- Glucokinase is an inducible enzyme and has high km value for glucose whereas hexokinase is a constitutive enzyme and has low km value for glucose.
- Steps: Uptake and Phosphorylation of Glucose → Isomerization of Glucose-6-Phsphate to Fructose-6-Phosphate → Phosphorylation of F-6-P to Fructose 1,6-Biphosphate → Cleavage of Fructose 1,6-Biphosphate → Interconversion of the Triose Phosphates → Oxidative phosphorylation of GAP to 1,3-Bisphosphoglycerate → Conversion of 1,3-Biphosphoglycerate to 3-Phosphoglycerate → Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate → Dehydration of 2-Phosphoglycerate to Phosphoenolpyruvate → Conversion of Phosphoenol Pyruvate to Pyruvate
Salient Features of Embden-Meyerhof Pathway
- Rate limiting step : Phosphofructokinase (PFK). PFK is stimulated by fructose-6-phosphate, AMP and ADP but is inhibited by ATP and citrate
- All the reactions of glycolysis are reversible except hexokinase, phosphofructokinase and pyruvate kinase catalyzed reactions because of energy barriers.
- Enzyme enolase is inhibited by fluoride. Since erythrocytes do not have mitochondrial enzymes to oxidize glucose aerobically, they depend on glycolysis only for their energy requirement. That is why sodium fluoride (NaF) is used in the collection of blood sugar sample because it prevents glycolysis by inhibiting the enzyme enolase. Otherwise a low result will be obtained due to glycolysis.
- It is the major pathway by which glucose is metabolized in erythrocytes.
- Pasteur effect is the inhibition of glycolysis by oxygen. The rate limiting step in glycolysis, the phosphofructokinase, is inhibited by citrate and ATP.
- Crabttee effect is the inhibition of cellular respiration by high concentrations of glucose. This is due to the completion of glycolytic processes for inorganic phosphate.
- Otto Warburg has studied glycolysis in various tissues.
- According to his studies, cancer cells utilize energy from glycolysis and they require less oxygen than their normal counterparts; this is called Warburg hypothesis (1923).
- Rapidly growing tumor cells produce increased quantities of lactic acid, causing high acidity in the local environment. When this lactate is used for gluconeogenesis by the liver; energy consumption
increases. This is one of the reasons for cancer cachexia (rapid loss of weight).
4 ATP + 2 NADH
- During anaerobic (oxygen deficient) condition, when one molecule of glucose is converted to 2 molecules of lactate, there is a net yield of 2 molecules of ATP.
- 4 molecules of ATP are synthesized by the 2 substrate level phosphorylations (steps 6 and 9). But 2 molecules of ATP are used in the steps 1 and 3, hence the net yield is only 2 ATP.
- The whole reaction is summarized as
Glucose + 2 Pi + 2 ADP –> 2 Lactate + 2 ATP
- 2 NADH molecules are generated in the glyceraldehyde- 3-phosphate dehydrogenase reaction (step 5).
The regulatory enzymes or key enzymes of EMP Pathway are:
- Glucokinase/Hexokinase, step 1
- Phosphofructokinase, step 3
- Pyruvate kinase, step 9