Glycolysis is the process by which glucose is converted into pyruvate and ATP. It is an essential metabolic pathway that occurs in all living organisms, from bacteria to humans. The word glycolysis comes from the Greek words “glykys,” meaning sweet, and “lysis,” meaning to break down.
Glycolysis occurs in the cytoplasm of the cell, and it is the first step in both aerobic and anaerobic respiration. In this article, we will explore the steps involved in glycolysis, the enzymes involved, and the overall significance of glycolysis in cellular metabolism.
Steps of Glycolysis
Glycolysis is a complex biochemical pathway that involves the conversion of glucose into pyruvate. The pathway can be broken down into ten steps, as outlined below:
Step 1: Phosphorylation of Glucose The first step of glycolysis involves the phosphorylation of glucose. Glucose is converted into glucose-6-phosphate (G6P) in the presence of the enzyme hexokinase. This reaction requires the input of energy in the form of ATP, and the reaction is irreversible.
Step 2: Isomerization of Glucose-6-Phosphate In the second step of glycolysis, glucose-6-phosphate is converted into fructose-6-phosphate (F6P) through the process of isomerization. This reaction is catalyzed by the enzyme phosphohexose isomerase.
Step 3: Phosphorylation of Fructose-6-Phosphate In the third step, fructose-6-phosphate is phosphorylated to form fructose-1,6-bisphosphate (FBP). This reaction is catalyzed by the enzyme phosphofructokinase-1 (PFK-1), and it requires the input of a second ATP molecule.
Step 4: Cleavage of Fructose-1,6-Bisphosphate In the fourth step, fructose-1,6-bisphosphate is cleaved into two three-carbon molecules, glyceraldehyde-3-phosphate (G3P), and dihydroxyacetone phosphate (DHAP). This reaction is catalyzed by the enzyme aldolase.
Step 5: Interconversion of Dihydroxyacetone Phosphate and Glyceraldehyde-3-Phosphate In the fifth step, dihydroxyacetone phosphate is converted into glyceraldehyde-3-phosphate through the process of isomerization. This reaction is catalyzed by the enzyme triose phosphate isomerase.
Step 6: Oxidation of Glyceraldehyde-3-Phosphate In the sixth step, glyceraldehyde-3-phosphate is oxidized to form 1,3-bisphosphoglycerate (1,3-BPG). This reaction is catalyzed by the enzyme glyceraldehyde-3-phosphate dehydrogenase, and it involves the transfer of a hydride ion to the coenzyme NAD+.
Step 7: Substrate-Level Phosphorylation In the seventh step, 1,3-bisphosphoglycerate is converted into 3-phosphoglycerate (3-PG) through the process of substrate-level phosphorylation. This reaction is catalyzed by the enzyme phosphoglycerate kinase, and it involves the transfer of a phosphate group from 1,3-BPG to ADP, producing ATP.
Step 8: Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate In the eighth step, 3-phosphoglycerate is converted into 2-phosphoglycerate (2-PG). This reaction is catalyzed by the enzyme phosphoglycerate mutase, and it involves the transfer of a phosphate group from the third carbon of 3-PG to the second carbon, forming 2-PG.
Step 9: Dehydration of 2-Phosphoglycerate In the ninth step, 2-phosphoglycerate is dehydrated to form phosphoenolpyruvate (PEP). This reaction is catalyzed by the enzyme enolase, and it involves the removal of a water molecule from 2-PG.
Step 10: Substrate-Level Phosphorylation In the final step of glycolysis, phosphoenolpyruvate is converted into pyruvate through the process of substrate-level phosphorylation. This reaction is catalyzed by the enzyme pyruvate kinase, and it involves the transfer of a phosphate group from PEP to ADP, producing ATP.
Enzymes Involved in Glycolysis
As mentioned earlier, glycolysis is a complex biochemical pathway that involves the action of several enzymes. Some of the key enzymes involved in glycolysis include:
- Hexokinase: This enzyme catalyzes the phosphorylation of glucose to form glucose-6-phosphate.
- Phosphohexose isomerase: This enzyme catalyzes the isomerization of glucose-6-phosphate to fructose-6-phosphate.
- Phosphofructokinase-1: This enzyme catalyzes the phosphorylation of fructose-6-phosphate to form fructose-1,6-bisphosphate.
- Aldolase: This enzyme catalyzes the cleavage of fructose-1,6-bisphosphate into two three-carbon molecules, glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.
- Triose phosphate isomerase: This enzyme catalyzes the isomerization of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate.
- Glyceraldehyde-3-phosphate dehydrogenase: This enzyme catalyzes the oxidation of glyceraldehyde-3-phosphate to form 1,3-bisphosphoglycerate.
- Phosphoglycerate kinase: This enzyme catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate through the process of substrate-level phosphorylation.
- Phosphoglycerate mutase: This enzyme catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate.
- Enolase: This enzyme catalyzes the dehydration of 2-phosphoglycerate to form phosphoenolpyruvate.
- Pyruvate kinase: This enzyme catalyzes the conversion of phosphoenolpyruvate to pyruvate through the process of substrate-level phosphorylation.
Significance of Glycolysis
Glycolysis is an essential metabolic pathway that is critical for the production of ATP. The ATP produced during glycolysis is used by the cell to carry out various functions, including muscle contraction, protein synthesis, and DNA replication. Glycolysis is also important because it provides the cell with a source of energy when oxygen is not available. This is because glycolysis can occur under both aerobic and anaerobic conditions.
In addition to its role in ATP production, glycolysis is also important because it provides the cell with building blocks for the synthesis of other molecules. For example, some of the intermediates produced during glycolysis can be used to synthesize amino acids, nucleotides, and fatty acids
stages in Glycolysis
Glycolysis is a complex metabolic pathway that occurs in the cytoplasm of cells and involves the breakdown of glucose into two molecules of pyruvate. It can be divided into two main stages: the energy investment phase and the energy payoff phase.
Energy Investment Phase The energy investment phase is the first stage of glycolysis and requires the input of energy in the form of two ATP molecules. During this stage, glucose is converted into fructose-1,6-bisphosphate, a six-carbon molecule. The following reactions occur during the energy investment phase:
Step 1: Phosphorylation of glucose In the first step, glucose is phosphorylated by the enzyme hexokinase, using one molecule of ATP, to form glucose-6-phosphate.
Glucose + ATP → Glucose-6-phosphate + ADP
Step 2: Isomerization of glucose-6-phosphate In the second step, glucose-6-phosphate is converted into fructose-6-phosphate by the enzyme phosphohexose isomerase.
Glucose-6-phosphate → Fructose-6-phosphate
Step 3: Phosphorylation of fructose-6-phosphate In the third step, fructose-6-phosphate is phosphorylated by the enzyme phosphofructokinase-1, using one molecule of ATP, to form fructose-1,6-bisphosphate.
Fructose-6-phosphate + ATP → Fructose-1,6-bisphosphate + ADP
Energy Payoff Phase The energy payoff phase is the second stage of glycolysis and involves the production of ATP and NADH. During this stage, fructose-1,6-bisphosphate is broken down into two molecules of glyceraldehyde-3-phosphate, each containing three carbons. The following reactions occur during the energy payoff phase:
Step 4: Cleavage of fructose-1,6-bisphosphate In the fourth step, fructose-1,6-bisphosphate is cleaved into two molecules of glyceraldehyde-3-phosphate by the enzyme aldolase.
Fructose-1,6-bisphosphate → 2 Glyceraldehyde-3-phosphate
Step 5: Isomerization of dihydroxyacetone phosphate In the fifth step, dihydroxyacetone phosphate, which is one of the products of the previous step, is converted into glyceraldehyde-3-phosphate by the enzyme triose phosphate isomerase.
Dihydroxyacetone phosphate ↔ Glyceraldehyde-3-phosphate
Step 6: Oxidation of glyceraldehyde-3-phosphate In the sixth step, glyceraldehyde-3-phosphate is oxidized by the enzyme glyceraldehyde-3-phosphate dehydrogenase, producing NADH and 1,3-bisphosphoglycerate.
Glyceraldehyde-3-phosphate + NAD+ + Pi → 1,3-bisphosphoglycerate + NADH + H+
Step 7: Substrate-level phosphorylation In the seventh step, 1,3-bisphosphoglycerate is converted into 3-phosphoglycerate by the enzyme phosphoglycerate kinase, producing ATP through the process of substrate-level phosphorylation.
1,3-bisphosphoglycerate + ADP → 3-phosphoglycerate + ATP
The above reactions occur twice per molecule of glucose, so the net result of glycolysis is the production of two molecules of ATP and two molecules of NADH, as well as two molecules of pyruvate.
Each molecule of glucose that enters the glycolytic pathway goes through the series of reactions described above twice, resulting in the production of two molecules of pyruvate, two molecules of ATP, and two molecules of NADH.
The two molecules of ATP are produced during the energy payoff phase, specifically in step 7 when 1,3-bisphosphoglycerate is converted into 3-phosphoglycerate by the enzyme phosphoglycerate kinase. This reaction is a type of substrate-level phosphorylation, which involves the transfer of a phosphate group from a substrate molecule (1,3-bisphosphoglycerate) to ADP, resulting in the formation of ATP.
The two molecules of NADH are produced during the energy payoff phase as well, specifically in step 6 when glyceraldehyde-3-phosphate is oxidized by the enzyme glyceraldehyde-3-phosphate dehydrogenase. This reaction involves the transfer of electrons from glyceraldehyde-3-phosphate to NAD+, resulting in the formation of NADH.
Overall, glycolysis is an important metabolic pathway that provides energy to cells by breaking down glucose, a simple sugar that can be derived from a variety of sources including dietary carbohydrates and stored glycogen. The products of glycolysis, such as ATP and NADH, can be further utilized by other cellular processes to support various biological functions.
