In glycolysis, step 9 is catalyzed by the enzyme enolase, which converts 2-phosphoglycerate into phosphoenolpyruvate (PEP) while releasing a water molecule. This reaction has a delta G close to 0, indicating that it is readily reversible under cellular conditions. The carbon numbering for the reactants and products is crucial: for 2-phosphoglycerate, the carbons are numbered 3, 4, 2, 5, and for PEP, they are 1 and 6. This step is part of a series of reactions that ultimately lead to the production of pyruvate.
Step 10, carried out by pyruvate kinase, is a significant reaction in glycolysis due to its highly negative delta G, making it a favorable and essentially irreversible step. In this reaction, PEP and ADP are converted into pyruvate and ATP through substrate-level phosphorylation. Pyruvate initially forms in its enol form before quickly converting to its keto form. The carbon numbering for PEP is 3, 4, 2, 5, and for pyruvate, it is 1 and 6.
It is important to note that while many glycolytic reactions are reversible, steps 1, 3, and 10 are considered commitment steps due to their negative delta G values, ensuring the pathway proceeds in one direction. Additionally, glycolysis can accommodate other substrates besides glucose, although entering the pathway will always incur an ATP cost. For instance, lactose is broken down into glucose and galactose, with glucose entering glycolysis as glucose 6-phosphate. Galactose undergoes several transformations before it can enter the pathway.
Fructose also enters glycolysis but requires conversion to fructose 1-phosphate, which is then split into glyceraldehyde and dihydroxyacetone phosphate (DHAP). Both of these can be converted into glyceraldehyde 3-phosphate (G3P), which is a key intermediate in glycolysis. Glycerol can also feed into glycolysis, but it is less efficient. Glycerol is converted to glycerol 3-phosphate, which then becomes G3P, using 1 ATP and generating 2 ATP. This results in a net gain of ATP, but glycerol produces excess NADH, which can hinder glycolysis under anaerobic conditions.
Furthermore, glycogen is stored in cells and, when broken down, is converted into glucose 1-phosphate by glycogen phosphorylase. This glucose 1-phosphate must then be converted to glucose 6-phosphate to enter glycolysis, illustrating the interconnectedness of carbohydrate metabolism.
