Glycolysis

There are three major pathways in cellular respiration: glycolysis, the citric acid cycle, and oxidative phosphorylation. Glycolysis is the first stage of cellular respiration and occurs in the cell cytoplasm. The products of glycolysis then enter the mitochondrion, where the citric acid cycle and oxidative phosphorylation occur. Most of the ATP made by the cell is produced in the mitochondrion through these later stages. The first major pathway in cellular respiration is glycolysis, the metabolic pathway in which glucose is broken down into pyruvate in the cytoplasm of the cell. Glycolysis takes place in the cell's cytoplasm, outside of the mitochondria. It is the first step in the process that converts glucose into energy. During glycolysis, a single glucose molecule is split into two molecules of pyruvate (also known as pyruvic acid). Importantly, glycolysis also generates two molecules of adenosine triphosphate (ATP). ATP is the main way cells transport energy. When ATP is hydrolyzed, broken down through the addition of water, it loses a phosphate group and becomes adenosine diphosphate (ADP). This is an exergonic process, a reaction that releases energy, and cells use the energy it releases to power other reactions. Another important product of glycolysis is nicotinamide adenine dinucleotide, which has an oxidized form, NAD⁺, and a reduced form, NADH. During glycolysis, two NAD⁺ molecules are reduced to form two NADH molecules.

NADH is an important electron carrier. The electrons will eventually help power the machinery that will produce most of the ATP when they are later donated to the electron transport chain, a series of electron transporters that move electrons from NADH and FADH₂ to oxygen molecules. Glycolysis only generates a small percentage of the ATP that can be produced from glucose, but the pyruvate produced can be used to produce energy via cellular respiration in the mitochondria.

Glycolysis involves 10 reactions. Each reaction has its own unique enzyme. It can be helpful to divide this pathway into an energy-investing phase, which is endergonic, and an energy-harvesting phase, which is exergonic. ATP is used during the energy-investing phase to power the glycolysis reaction; ATP is produced during the energy-harvesting phase. The net reaction for glycolysis can be summarized as:

The first half of glycolysis, the energy-investment phase, involves five steps:

Step 1. The enzyme hexokinase is used to phosphorylate glucose. Phosphorylation is the addition of a phosphate group to a molecule in a chemical reaction. ATP is the source of the phosphate; an ATP molecule is oxidized to form glucose 6-phosphate.

Step 2. Phosphoglucose isomerase is the enzyme used to convert glucose 6-phosphate to fructose 6-phosphate. Fructose 6-phosphate is an isomer (a molecule with the same molecular formula as another molecule but with a different structure) of glucose 6-phosphate. An isomerase is an enzyme that drives the conversion of a molecule into its isomer form.

Step 3. Phosphofructokinase is the enzyme that oxidizes ATP to phosphorylate the molecule on one end of fructose 6-phosphate. In glycolysis, phosphofructokinase is a rate-limiting enzyme. There is less activity from this enzyme when ADP levels are low and the concentration of ATP is high. It is more active when ADP concentration is high. When there is sufficient ATP in the system, this step of the pathway slows down. At this point along the glycolysis pathway, two ATP molecules have been used, resulting in the production of fructose 1,6-bisphosphate.

Step 4. Aldolase breaks fructose 1,6-bisphosphate into two different three-carbon sugars. These three-carbon sugars are dihydroxyacetone-phosphate (DAP) and glyceraldehyde 3-phosphate (G3P).

Step 5. Triose phosphate isomerase converts DAP to G3P, which is an isomer of DAP. This reaction is fully reversible but proceeds in this direction because the G3P is immediately used as a reactant for Step 6, the beginning of the energy-harvesting phase.

The second half of glycolysis, the energy-harvesting phase, involves five steps.

Step 6. The enzyme glyceraldehyde 3-phosphate dehydrogenase catalyzes a two-step reaction. The first reaction oxidizes G3P with the coenzyme NAD⁺ to make NADH. Energy is produced from this reaction to power the second reaction, where a phosphate group is oxidized to form 1,3-bisphosphoglycerate.

Step 7. The enzyme phosphoglycerate kinase catalyzes the transfer of a phosphate from 1,3-bisphosphoglycerate to ADP. This phosphorylation reaction is done to make ATP and the product 3-phosphoglycerate.

Step 8. Phosphoglycerate mutase rearranges the phosphate in 3-phosphoglycerate to make 2-phosphoglycerate.

Step 9. Enolase removes a water molecule from 2-phosphoglycerate. This hydrolysis reaction, the process by which the water molecule is removed, results in the formation of a double bond between two carbon atoms. Phosphoenolpyruvate is also produced.

Step 10. The enzyme pyruvate kinase catalyzes the transfer of a phosphate from phosphoenolpyruvate to ADP. This results in the formation of pyruvate and ATP.