. Once transported into the cell, glucose is phosphorylated to G6P by hexokinases (Hk). Phosphoglucose isomerase (Gpi) converts G6P to F6P which is then phosphorylated to FBP by phosphofrucokinases (Pfk) in the second energy-consuming and the most important rate-determining step of the pathway. In reaction 4, aldolases (Aldo) cleave FBP to two trioses: GAP and DHAP. Only GAP is further used in the pathway; the isomerization of the two ketose-aldose isomers is carried out by triose phosphate isomerase (Tpi1) in the 5th and final reaction of stage I. Reactions 6 and 7 are coupled: the glyceraldehyde-3-phosphate dehydrogenase (Gapdh)-catalyzed reaction yields the 'high-energy' 1,3-BPG and in the process NAD⁺ is reduced to NADH; the phosphoglycerate kinase (Pgk1)-mediated reaction yields ATP and 3PG. The interconversion of 3PG to 2PG is carried out by phosphoglycerate mutase (Pgam). 2PG is dehydrated by enolases (Eno) to form the second 'high-energy' compound PEP. In reaction 10, the final step of stage II, pyruvate kinases yield ATP and pyruvate. Under aerobic conditions, pyruvate can be completely oxidized in the citric acid cycle pathway, the second round of breakdown. Under anaerobic conditions pyruvate is converted to lactate (muscle). Pyruvate can also be used to regenerate glucose (gluconeogenesis pathway). As necessary, glucose can be stored as glycogen, converted to other sugars or used to generate NADPH. The substrate ATP is also an allosteric inhibitor of phosphofructokinase - the enzyme of the major rate-limiting step of glycolysis. AMP, ADP and F2,6P are activators (the concentration of the latter is the outcome of its synthesis/degradation cycle mediated by Pfkfb members - bifunctional enzymes that are heavily regulated). Phosphofructokinase is a tetramer with two conformational states R and T that are in equilibrium. The F6P substrate, the ATP substrate or inhibitor and the activators modulate the level of enzyme activity via preferential binding to the R or T state. To see the ontology report for annotations, GViewer and download, click here. [Click to see the ontology report for associated GO term - GO:0006096, related KEGG map - map00010 and entry at Reactome - REACT_1383.5]...(less)