In the first half of glycolysis, energy in the form of two ATP molecules is required to transform glucose into two three-carbon molecules.
- Outline the energy-requiring steps of glycolysis
- ATP molecules donate high energy phosphate groups during the two phosphorylation steps, step 1 with hexokinase and step 3 with phosphofructokinase, in the first half of glycolysis.
- In steps 2 and 5, isomerases convert molecules into their isomers to allow glucose to be split eventually into two molecules of glyceraldehyde-3-phosphate, which continues into the second half of glycolysis.
- The enzyme aldolase in step 4 of glycolysis cleaves the six-carbon sugar 1,6-bisphosphate into two three-carbon sugar isomers, dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate.
- glucose: a simple monosaccharide (sugar) with a molecular formula of C6H12O6; it is a principal source of energy for cellular metabolism
- adenosine triphosphate: a multifunctional nucleoside triphosphate used in cells as a coenzyme, often called the “molecular unit of energy currency” in intracellular energy transfer
First Half of Glycolysis (Energy-Requiring Steps)
In the first half of glycolysis, two adenosine triphosphate (ATP) molecules are used in the phosphorylation of glucose, which is then split into two three-carbon molecules as described in the following steps.
Step 1. The first step in glycolysis is catalyzed by hexokinase, an enzyme with broad specificity that catalyzes the phosphorylation of six-carbon sugars. Hexokinase phosphorylates glucose using ATP as the source of the phosphate, producing glucose-6-phosphate, a more reactive form of glucose. This reaction prevents the phosphorylated glucose molecule from continuing to interact with the GLUT proteins. It can no longer leave the cell because the negatively-charged phosphate will not allow it to cross the hydrophobic interior of the plasma membrane.
Step 2. In the second step of glycolysis, an isomerase converts glucose-6-phosphate into one of its isomers, fructose-6-phosphate. An enzyme that catalyzes the conversion of a molecule into one of its isomers is an isomerase. (This change from phosphoglucose to phosphofructose allows the eventual split of the sugar into two three-carbon molecules).
Step 3. The third step is the phosphorylation of fructose-6-phosphate, catalyzed by the enzyme phosphofructokinase. A second ATP molecule donates a high-energy phosphate to fructose-6-phosphate, producing fructose-1,6-bisphosphate. In this pathway, phosphofructokinase is a rate-limiting enzyme. It is active when the concentration of ADP is high; it is less active when ADP levels are low and the concentration of ATP is high. Thus, if there is “sufficient” ATP in the system, the pathway slows down. This is a type of end-product inhibition, since ATP is the end product of glucose catabolism.
Step 4. The newly-added high-energy phosphates further destabilize fructose-1,6-bisphosphate. The fourth step in glycolysis employs an enzyme, aldolase, to cleave 1,6-bisphosphate into two three-carbon isomers: dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate.
Step 5. In the fifth step, an isomerase transforms the dihydroxyacetone-phosphate into its isomer, glyceraldehyde-3-phosphate. Thus, the pathway will continue with two molecules of a single isomer. At this point in the pathway, there is a net investment of energy from two ATP molecules in the breakdown of one glucose molecule.