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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)

  • This phase involves the initial consumption of ATP to prepare glucose for subsequent breakdown, and it includes the following steps:

1) Phosphorylation of Glucose:

  • The enzyme hexokinase catalyzes the phosphorylation of glucose to form glucose-6-phosphate (G6P), utilizing one ATP molecule, which is converted to ADP.

2) Isomerization:

  • Phosphoglucose isomerase is then isomerized to fructose-6-phosphate (F6P) by the enzyme phosphoglucose isomerase.

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:

  • 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 leads to the production of ATP and NADH by processing the glyceraldehyde-3-phosphate molecules through the following steps:

  • 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:

  • 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:

  • 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

  • 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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