Principles of glycolysis

What is Glycolysis?

Glycolysis is a series of enzyme-catalysed reactions that extract energy from glucose. This step is the first process involved in cellular respiration. This can be both an aerobic or anaerobic process that involves almost 10 steps and takes place in the cell’s cytosol. The word “Glycolysis” is derived from the Greek words – “glykys” meaning sweet, and “lysis”, meaning splitting.

The Process of Glycolysis

Glycolysis involves a series of 10 steps and can be broken down into two major phases – 

1. The energy-requiring phase or the Preparatory phase: this phase involves the first 5 steps

2. The energy-releasing phase or the Payoff phase: this phase involves the following 5 steps

STEP-1:

In this step, in the presence of the catalyst hexokinase, a phosphate group is transferred to glucose from ATP, leading to the formation of glucose-6-phosphate

STEP-2: 

In this step, in the presence of the catalyst phosphoglucose isomerase, glucose-6-phosphate is converted to its isomer fructose-6-phosphate

STEP-3: 

In this step, in the presence of the catalyst phosphofructokinase, the phosphate group is transferred from ATP to fructose-6-phosphate, leading to the formation of fructose-1,6-bisphosphate 

STEP-4:

 In this step, in the presence of the catalyst fructose bisphosphate aldolase, fructose-1,6 bisphosphate get split into three-carbon sugars – dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate

STEP-5:

 In this step, in the presence of the catalyst fructose triosephosphate isomerase, DHAP is converted to two molecules initially in equilibrium – Dihydroxyacetone phosphate and Glyceraldehyde-3-phosphate

Gradually pushing reaction towards the latter

STEP-6:

In this step, in the presence of the catalyst pyruvate kinase, two half-reactions coincide – Glyceraldehyde-3-phosphate is oxidised and NAD+ is reduced to NADH and H+. The overall process is exergonic, aiding to phosphorylate the molecule to 1,3-bisphosphoglycerate

STEP-7: 

In this step, in the presence of the catalyst phosphoglycerate kinase, 1,3-bisphosphoglycerate formed in step-6 donates one of its phosphate groups to ADP, forming a molecule of ATP gradually forming 3-phosphoglycerate

STEP-8: 

In this step, in the presence of the catalyst phosphoglycerate mutase, 3-phosphoglycerate is converted into 2-phosphoglycerate, its isomer.

STEP-9:

 In this step, in the presence of the catalyst enolase, 2-phosphoglycerate loses a water molecule, leading to the formation of phosphoenolpyruvate (PEP), an unstable molecule.

STEP-10:

 In this step, in the presence of the catalyst Pyruvate kinase, PEP donates its phosphate group to ADP, leading to a second molecule of ATP. PEP is converted to pyruvate upon loss of its phosphate, which is the end of the glycolysis process.

Conclusion:

So, to put it in simpler words, Glycolysis is a metabolic pathway that involves the conversion of glucose to pyruvic acid and the utilisation of free energy released in this process to form ATP molecules and NADH molecules.

Ways to Regulate Flux Through a Metabolic Pathway:

1. Availability of substrate :

• GLUT1 (Kt 1.5 mM) vs GLUT2 (Kt 66 mM)

• Insulin-responsive GLUT4

2. The concentration of enzymes is responsible for rate-limiting steps. Insulin stimulates the transcription of the genes that encode –

• Hexokinase

• Phosphofructokinase-1 

• Pyruvate kinase 

• PFK-2/FBPase-2

3. Allosteric regulation of enzymes:

• Allosteric activator/inhibitor

4. Covalent modification of enzymes:

• Phosphorylation