Glycolysis: Pathway, energetics, and regulation

1. Introduction
  • Also known as Embden-Meyerhof Pathway
  • Term is derived from two Greek words- "Glycos" means sweet and "Lysis" means splitting).
  • It is the conversion of glucose (or glycogen) into pyruvate (under aerobic condition) or lactate (under anaerobic condition).
  • Takes place in every cell.
  • Enzymes of the pathway are present in cytoplasm of the cell.
  • Total 10 step process:
    • First 5 steps are Preparatory phase (From 1 mole of glucose to 2 mole of glyceraldehyde-3-phosphate).
    • Next 5 steps are Payoff phase (From 2 mole of glyceraldehyde-3-phosphate to 2 mole of pyruvate).
2. Detailed pathway
3. Summary of pathway

Glucose + 2 ATP + 2 NAD+ + 4 ADP + 2 Pi ⇒⇒⇒ 2 Pyruvate + 2 ADP + 2 NADH + 2H+ + 4 ATP + 2 H2O

4. Significance of glycolysis (total energy generated)

From 2 NADH (1 NADH yields 3 ATP)
6 ATP
Direct ATP generated in pathway
4 ATP
ATP utilized in pathway                                                  
-2 ATP
Net Gain of ATP in pathway                                             
8 ATP

5. Under anaerobic conditions
  • Pruvate is reduced to lactate utilizing 2 NADH (equivalent to 6 ATP).
  • Hence, net gain of ATP in anaerobic condition is 2ATP.
  • The importance of this conversion is that, under anaerobic condition, NADH cannot be converted back (re-oxidized) into NAD, which is essential for glycolysis to continue.
  • If NAD will not be available, glycolysis would stop.
  • Hence, in order to continue glycolysis, pyruvate is reduced to lactate, accepting electrons from NADH and thereby regenerating the NAD necessary.
  • This allows the regeneration of NAD which can be reused in glycolysis in the absence of oxygen.

6. Regulation of glycolysis

There are three enzymes (called as regulators) which regulate the pathway: 

i. Hexokinase
  • Inhibited by glucose 6-phosphate (product inhibition). 
ii. Phosphofructokinase (most important regulator)
  • Allosteric enzyme regulated by-
    • Inhibitors: citrate, H+ ions, ATP.
    • Activators: fructose 2,6-bisphosphate, ADP, AMP, Pi.
iii. Pyruvate kinase
  • Inhibitor: ATP, Glucagon.
  • Activator: Fructose 1,6-bisphosphate.

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