Glycolysis is the metabolic pathway by which glucose is oxidized or broken down to pyruvate. It is the pathway that carries out glucose degradation in living systems including microbes. Glycolysis (which is the metabolic breakdown of glucose to release energy meant for cellular and metabolic work in the cell) can also be called Embden Meyerhof pathway (EMP). The glycolytic pathway regulates gluconeogenesis, which is the metabolic process of maintaining the blood glucose levels of living systems (especially when they are depleted) by making glucose from pyruvate. Gluconeogenesis is generally the biosynthesis of glucose from pyruvate when the blood glucose level is low. Aside the degradation of glycogen (the form in which sugar is stored in animals) to release glucose for the cell; glucose can also be made available for the cell via the process of gluconeogenesis which usually takes place in the kidney and liver of animals. The glycolytic pathway is a catabolic pathway that produces energy in the form of ATP for the cell; and due to the significant biological roles of glucose in the cells of microbes and other higher organisms including humans, plants and animals, glycolysis is a key metabolic pathway for the oxidation of glucose to carbon and water during which ATP is released in sufficient amount for cellular and metabolic work. However, glycolysis may take part in some anabolic reactions in the cell especially when some intermediates from the glycolytic pathways are utilized for the biosynthesis of other cellular macromolecules.
Glycolysis occurs in the cytosol of the cell; and this vital metabolic process occurs in both aerobic and anaerobic conditions in eukaryotic and prokaryotic cells. It occurs during substrate-level phosphorylation, oxidative phosphorylation and in fermentation reaction. Different amounts of ATP are formed during each of these processes. In the glycolytic pathway, one molecule of glucose yields two molecules each of pyruvate, NADH and two molecules of ATP via substrate-level phosphorylation. But in oxidative phosphorylation, the pyruvate is converted to acetyl-CoA which enters the tricarboxylic acid (TCA) cycle and then the electron transport chain (ETC) as shall be seen where NADH (an electron carrier) is oxidized for the production of sufficient amount of ATP for the cell. The glycolytic pathway is a ten (10) step reaction that catalyzes the breakdown of glucose to pyruvate (Figure 1). Adenosine diphosphate (ADP) is also phosphorylated to adenosine triphosphate (ATP) during glycolysis; and this serves as source of high-energy for the cell. Electron transport chain (ETC) is described in detail in the subsequent section.
The first product of the glycolytic pathway is glucose-6-phosphate while pyruvate (a three-carbon compound) is the final product of glycolysis. Pyruvate after its production in the glycolytic pathway has three different fates – which are also important in other cellular and metabolic activities of the cell in which the processes occurs. These fates of pyruvate are highlighted in this section.
- In anaerobic conditions (e.g., in fermentation), the pyruvate can be converted to ethanol in yeast cells; and this activity is of immense application in industries where yeast cells are utilized for the production of goods and products that are of economic importance.
- In aerobic conditions, the pyruvate can be oxidized to produce acetyl-CoA which is an important precursor of the TCA cycle. The acetyl-CoA enters the TCA cycle where it is oxidized to water and carbon dioxide (CO2). And the process continues into the ETC where energy in the form of ATP is generated for cellular and metabolic work in microbial cells, plants and animal cells as well.
- In conditions of low oxygen concentration in the cell (e.g. in muscle cells), pyruvate can be reduced to lactate through lactic acid fermentation to generate energy for the cell. This is an anaerobic process like the aforementioned conversion of pyruvate to ethanol.
Generally, glycolysis has two phases viz: the preparatory or initiation stage and the pay-off stage. In the preparatory stage, ATP is not generated but instead ATP it is utilized and hydrolyzed to ADP. Energy is lost in the preparatory stage. Fructose 1,6-bisphosphate is the last product of the preparatory stage of glycolysis; and this molecule is converted to glyceraldehyde 3-phosphate (the first precursor of the pay-off stage of glycolysis). The preparatory stage of glycolysis is characterized by the phosphorylation of glucose and its conversion to glyceraldehyde 3-phosphate from fructose 1,6-bisphosphate. The pay-off stage is marked by a remarkable energy gain. In the pay-off stage, ADP is phosphorylated to ATP; and it is at this stage that pyruvate (the end product of the glycolytic pathway) is formed. Glyceraldehyde 3-phosphate is oxidatively converted to pyruvate (Figure 1) in the pay-off stage. And energy is conserved as ATP and NADH in the pay-off stage of glycolysis.
Figure 1: Schematic illustration of the glycolytic pathway. Glycolysis is an enzyme-catalyzed redox reaction in which glucose is oxidized or broken down to pyruvate.
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