kEY IRREVERSIBLE REACTIONS OF GLYCOLYSIS REACTIONS

 What is Glycolysis?

Glycolysis or Embden–Meyerhof–Parnas pathway was the first pathway elucidated. Meyerhof won the noble prize in 1922 in physiology and medicine for his discovery to find fixed relationship between lactic acid utilisation in muscles and expenditure of oxygen.

The word glycolysis is derived from Greek word "glykys" means sweet and "lysis" means splitting. So, the glycolysis involves the splitting of 1 glucose molecule into 2 pyruvate molecules. Moving on the pyruvate have two fate, whether converted into the acetyl-CO-A in the presence of oxygen or Lactate in the absence of oxygen. 

Summarising the glycolysis, it involves the 10 reactions that take place in cytosol and generate 2 ATP molecules. Despite taking place in the cytosol, yet evolved even before oxygen was present in the Earth's atmosphere. 

Irreversible Reactions of Glycolysis

Three irreversible reactions of glycolysis are regulatory steps involve 3 key enzymes hexokinase, phospho-fructokinase, and pyruvate kinase. These enzymes have large negative ΔG values which shift the flux irreversibly in forward direction. 

Some of the key quick side role of glycolytic pathway intermediates governed by these 3 enzymes are given below:

1. The enzyme hexokinase (glucokinase) converting the glucose into Glucose-6-Phosphate. G-6-P  can enter the Pentose Phosphate Pathway and generate NADPH by reducing the NAD+ which overall maintain the antioxidant capacity of cell. G-6-P can also generate the glycogen. 

2. Phosphofructo kinase-I enzyme converting the fructose-6-phosphate into fructose-1,6-bisphosphate, another step which irreversibly move the flux in forward direction.

3. Pyruvate kinase enzyme, which convert the phosphoenol pyruvate (PEP) into pyruvate and this pyruvate also has a quick side role in the synthesis of alanine amino acid synthesis. 

How reactions drive in forward direction?

The initial reactant concentration (glucose), enzyme concentration and activity, and ΔG decide the direction of pathway. The overall free Gibbs energy (ΔG) for glycolysis occurring in erythrocytes is –96 kJ/mol and it favour the flux in forward direction. These three steps do go in reverse direction during gluconeogenesis irreversibly and convert the pyruvate into glucose. 

During the reactions of glycolysis to maintain the low ratio of concentration between product & reactant and - ΔG, the product of each reaction is quickly removed by the subsequent reaction in order to favour the glycolysis.

Negative ΔG values of 3 Irreversible steps of Glycolysis