Glycolysis – Pathway, energetics, and significance

• Glycolysis is a pivotal biochemical pathway in the metabolism of glucose, leading to the production of pyruvate, ATP (adenosine triphosphate), and NADH (nicotinamide adenine dinucleotide).
• It occurs in the cytoplasm of cells and operates under anaerobic conditions, meaning it does not require oxygen.
• This process plays a critical role in generating energy and precursor molecules necessary for various cellular functions.
• The pathway of glycolysis is systematically organized into two main phases: the energy investment phase (preparatory phase) and the energy generation phase (payoff phase), each comprising specific enzymatic reactions.

Energy Investment Phase (Preparatory Phase)

• The energy investment phase of glycolysis involves the initial consumption of ATP to prepare glucose for further breakdown.
• The steps are as follows:

1. Phosphorylation of Glucose

   • The enzyme hexokinase phosphorylates glucose, forming glucose-6-phosphate (G6P), using 1 ATP, which is converted to ADP.

2. Isomerization of Glycolysis

   • Phosphoglucose isomerase converts glucose-6-phosphate into fructose-6-phosphate (F6P).

3. Second Phosphorylation

   • Phosphofructokinase-1 (PFK-1) phosphorylates fructose-6-phosphate to form fructose-1,6-bisphosphate (F1,6BP), consuming another 1 ATP.

4. Cleavage of Glycolysis

   • Aldolase cleaves fructose-1,6-bisphosphate into two 3-carbon molecules: glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).

5. Isomerization of DHAP

   • Triose phosphate isomerase converts dihydroxyacetone phosphate (DHAP) into another glyceraldehyde-3-phosphate (G3P).
   • Now, two G3P molecules enter the energy generation phase.

Energy Generation Phase (Payoff Phase)

• This phase produces ATP and NADH by processing the two glyceraldehyde-3-phosphate molecules formed in the investment phase.
• The steps are as follows:

1. Oxidation and Phosphorylation

   • Each G3P is oxidized and phosphorylated by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to form 1,3-bisphosphoglycerate (1,3BPG), generating 1 NADH per G3P (2 NADH in total).

2. ATP Formation of Glycolysis

   • 1,3-bisphosphoglycerate donates a phosphate to ADP, forming ATP and 3-phosphoglycerate (3PG) via phosphoglycerate kinase. This step produces 2 ATP molecules (one per G3P).

3. Conversion to 2-Phosphoglycerate

   • Phosphoglycerate mutase converts 3-phosphoglycerate to 2-phosphoglycerate (2PG).

4. Dehydration of Glycolysis

   • Enolase dehydrates 2-phosphoglycerate to form phosphoenolpyruvate (PEP).

5. ATP and Pyruvate Formation

   • Pyruvate kinase transfers a phosphate from PEP to ADP, forming ATP and pyruvate. This produces 2 ATP molecules (one per G3P).

Energetics of Glycolysis

• Net ATP Gain: 2 ATP (4 ATP produced, 2 consumed).
• NADH Production: 2 NADH, which can further contribute to ATP production via oxidative phosphorylation.

Significance of Glycolysis

• Glycolysis is significant for several reasons:
  • Provides a rapid ATP source, especially under anaerobic conditions.
  • Produces pyruvate for further aerobic or anaerobic metabolism.
  • Central to cellular energy metabolism and the synthesis of precursor molecules.
• This concise overview highlights the importance of glycolysis in energy production and metabolic

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