What is Glycolysis? Explain the Phases of Glycose oxidative pathway at cellular levels?

Glycolysis can occur with or without oxygen. In the presence of oxygen, glycolysis is the first stage of cellular respiration. Without oxygen, glycolysis allows cells to make small amounts of ATP. This process is called fermentation.

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Phases and Stages of Glycolysis

The Glucose catabolic pathway can be divided into two Phases. They are the Preparative Phase and Payoff Phase.

Glycolytic Phase 1: Preparative Phase

Step 1: Phosphorylation

The enzyme hexokinase phosphorylates (adds a phosphate group to) glucose in the cell’s cytoplasm. In the process, a phosphate group from ATP is transferred to glucose producing glucose 6-phosphate.

Glucose (C₆H₁₂O₆) + hexokinase + ATP → ADP + Glucose 6-phosphate (C₆H₁₁O₆P₁)

Step 2: Isomerization

The enzyme phosphoglucoisomerase converts glucose 6-phosphate into its isomer fructose 6-phosphate. Isomers have the same molecular formula, but the atoms of each molecule are arranged differently.

Glucose 6-phosphate (C₆H₁₁O₆P₁) + Phosphoglucoisomerase → Fructose 6-phosphate (C₆H₁₁O₆P₁)

Step 3: Phosphorylation

The enzyme phosphofructokinase uses another ATP molecule to transfer a phosphate group to fructose 6-phosphate to form fructose 1, 6-bisphosphate.

Fructose 6-phosphate (C₆H₁₁O₆P₁) + phosphofructokinase + ATP → ADP + Fructose 1, 6-bisphosphate (C₆H₁₀O₆P₂)

Step 4: Cleavation

The enzyme aldolase splits fructose-1,6-bisphosphate into two sugars that are isomers of each other. These two sugars are dihydroxyacetone phosphate and glyceraldehyde phosphate.

Fructose 1, 6-bisphosphate (C₆H₁₀O₆P₂) + aldolase → Dihydroxyacetone phosphate (C₃H₅O₃P₁) + Glyceraldehyde phosphate (C₃H₅O₃P₁)

Step 5: Isomerization

The enzyme triose phosphate isomerase rapidly inter-converts the molecules dihydroxyacetone phosphate and glyceraldehyde phosphate. Glyceraldehyde phosphate is removed as soon as it is formed to be used in the next step of glycolysis.

Dihydroxyacetone phosphate (C₃H₅O₃P₁)   →     Glyceraldehyde phosphate (C₃H₅O₃P₁)

The net result for steps 4 and 5:

Fructose 1, 6-bisphosphate (C₆H₁₀O₆P₂)   ↔ 2 molecules of Glyceraldehyde phosphate (C₃H₅O₃P₁)

Glycolytic Phase 2: Payoff Phase

Step 6: Oxidative phosphorylation

The enzyme triose phosphate dehydrogenase serves two functions in this step. First, the enzyme transfers hydrogen (H^–) from glyceraldehyde phosphate to the oxidizing agent nicotinamide adenine dinucleotide (NAD⁺) to form NADH. Next triose phosphate dehydrogenase adds a phosphate (P) from the cytosol to the oxidized glyceraldehyde phosphate to form 1, 3-bisphosphoglycerate. This occurs for both molecules of glyceraldehyde phosphate produced in step 5.

A. Triose phosphate dehydrogenase + 2 H^– + 2 NAD⁺ → 2 NADH + 2 H⁺

B. Triose phosphate dehydrogenase + 2 P + 2 glyceraldehyde phosphate (C₃H₅O₃P₁)

             → 2 molecules of 1,3-bisphosphoglycerate (C₃H₄O₄P₂)

Step 7: Dephosphorylation

The enzyme phosphoglycerokinase transfers a P from 1,3-bisphosphoglycerate to a molecule of ADP to form ATP. This happens for each molecule of 1,3-bisphosphoglycerate. The process yields two 3-phosphoglycerate molecules and two ATP molecules.

2 molecules of 1,3-bisphoshoglycerate (C₃H₄O₄P₂) + phosphoglycerokinase + 2 ADP

                                              → 2 molecules of 3-phosphoglycerate (C₃H₅O₄P₁) + 2 ATP

Step 8: Isomerization

The enzyme phosphoglyceromutase relocates the ~P from 3-phosphoglycerate from the third carbon to the second carbon to form 2-phosphoglycerate.

2 molecules of 3-Phosphoglycerate (C₃H₅O₄P₁) + phosphoglyceromutase  → 2 molecules of 2-Phosphoglycerate (C₃H₅O₄P₁)

Step 9: Dehydration

The enzyme enolase removes a molecule of water from 2-phosphoglycerate to form a Phosphoenolpyruvic acid (PEP). This happens for each molecule of 2-phosphoglycerate.

2 molecules of 2-Phosphoglycerate (C₃H₅O₄P₁) + enolase → 2 molecules of phosphoenolpyruvic acid (PEP) (C₃H₃O₃P₁)

Step 10: Phosphorylation

The enzyme pyruvate kinase transfers a ~P from PEP to ADP to form pyruvic acid and ATP. This happens for each molecule of PEP. This reaction yields 2 molecules of pyruvic acid and 2 ATP molecules.

2 molecules of PEP (C₃H₃O₃P₁) + pyruvate kinase + 2 ADP → 2 molecules of pyruvic acid (C₃H₄O₃) + 2 ATP

Summary

In summary, a single glucose molecule in glycolysis produces a total of 2 molecules of pyruvic acid, 2 molecules of ATP, 2 molecules of NADH, and 2 molecules of water.

Although 2 ATP molecules are used in steps 1-3, 2 ATP molecules are generated in step 7 and 2 more in step 10. This gives a total of 4 ATP molecules produced. If you subtract the 2 ATP molecules used in steps 1-3 from the 4 generated at the end of step 10, you end up with a net total of 2 ATP molecules produced. For a detailed view of the 10 steps, see Details of the 10 Steps of Glycolysis.