Glycolysis

Learning Objectives for this Section

Function: Glycolysis (def) is a partial breakdown of a six-carbon glucose molecule into two, three-carbon molecules of pyruvate, 2NADH +2H⁺, and 2 net ATP as a result of substrate-level phosphorylation (def), as shown in (see Fig. 1 and 2). Glycolysis occurs in the cytoplasm of the cell. The overall reaction is:

glucose (6C) + 2 NAD⁺ 2 ADP +2 inorganic phosphates (P_i)

yields 2 pyruvate (3C) + 2 NADH + 2 H⁺ + 2 net ATP

Glycolysis also produces a number of key precursor metabolites (def), as shown in Fig. 3.

Glycolysis does not require oxygen and can occur under aerobic and anaerobic conditions. However, during aerobic respiration, the two reduced NADH molecules (def) transfer protons and electrons to the electron transport chain (def) to generate additional ATPs by way of oxidative phosphorylation (def).

The glycolysis pathway involves 9 distinct steps, each catalyzed by a unique enzyme. You are not responsible for knowing the chemical structures or enzymes involved in the steps below. They are included to help illustrate how the molecules in the pathway are manipulated by the enzymes in order to to acheive the required products.

1. To initiate glycolysis in eukaryotic cells (see Fig. 4), a molecule of ATP is hydrolyzed to transfer a phosphate group to the number 6 carbon of glucose to produce glucose 6-phosphate. In prokaryotes, the conversion of phosphoenolpyruvate (PEP) to pyruvate provides the energy to transport glucose across the cytoplasmic membrane and, in the process, adds a phosphate group to glucose producing glucose 6-phosphate. (See group translocation in Unit 1.)

2. The glucose 6-phosphate is rearranged to an isomeric form (def) called fructose 6-phosphate (see Fig. 5).

3. A second molecule of ATP is hydrolyzed to transfer a phosphate group to the number 1 carbon of fructose 6-phosphate to produce fructose 1,6-biphosphate (see Fig. 6).

4. The 6-carbon fructose 1,6 biphosphate is split to form two, 3-carbon molecules: glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The dihydroxyacetone phosphate is then converted into a second molecule of glyceraldehyde 3-phosphate (see Fig. 7). Two molecules of glyceraldehyde 3-phosphate will now go through each of the remaining steps in glycolysis producing two molecules of each product.

5. As each of the two molecules of glyceraldehyde 3-phosphate are oxidized, the energy released is used to add an inorganic phosphate group to form two molecules of 1,3-biphosphoglycerate, each containing a high-energy phosphate bond. During these oxidations, two molecules of NAD⁺ are reduced to form 2NADH + 2H⁺ (see Fig. 8). During aerobic respiration, the 2NADH + 2H⁺ carry protons and electrons to the electron transport chain to generate additional ATP by oxidative phosphorylation (def).

6. As each of the two molecules of 1,3-biphosphoglycerate are converted to 3-phosphoglycerate, the high-energy phosphate group is added to ADP producing 2 ATP by substrate-level phosphorylation (def), a shown in Fig. 9.

7. The two molecules of 3-phosphoglycerate are rearranged to form two molecules of 2-phosphoglycerate (see Fig. 10).

8. Water is removed from each of the two molecules of 2-phosphoglycerate converting the phosphate bonds to a high-energy phosphate bonds as two molecules of phosphoenolpyruvate are produced (see Fig. 11).

9. As the two molecules of phosphoenolpyruvate are converted to two molecules of pyruvate, the high-energy phosphate groups are added to ADP producing 2 ATP by substrate-level phosphorylation (def), a shown in Fig. 12.

Through an intermediate step called the transition reaction, the two molecules of pyruvate then enter the citric acid cycle to be further broken down and generate more ATPs by oxidative phosphorylation (def).

GLYCOLYSIS