e to PEP, the inverse of reaction 10 of glycolysis is carried out in two steps. In step 1 pyruvate carboxylase (Pc) converts pyruvate to oxaloacetate which is converted to PEP by PEP carboxykinase (Pck) in step 2. Reaction 10 of glycolysis, as well as reactions 3 and 1 are exergonic; thus, the reverse steps must be carried out by enzymes that can render them thermodynamically favorable. The enzymes unique to gluconegenesis are colored purple to distinguish them from enzymes that are shared by both pathways. Pc is a biotin-containing enzyme allosterically regulated by acetyl-CoA and aspartate. The formation of oxaloacetate from pyruvate or citric acid cycle intermediates occurs in the mitochondrion whereas the PEP to glucose pathway is cytosolic. PEP transport across the mitochondrial membrane is carried out by specific transporters; oxaloacetate transport requires conversion to either aspartate (known as Route 1) or to malate (Route 2). The aspartate aminotransferase route (1) and the malate dehydrogenase route (2) differ in that the latter involves the transport of reducing equivalents. From PEP to FBP, the reactions are mediated by the glycolytic enzymes working in reverse. The hydrolysis of FBP to F6P and the hydrolysis of G6P to glucose are catalyzed by gluconeogenesis-specific enzymes. FBP is hydrolyzed by fructose-1,6-bisphosphatase (Fbp); G6P is hydrolyzed by glucose-6-phosphatase. Fbp(s) are inhibited by F2,6P. The net concentration of F2,6P is the outcome of its synthesis/degradation cycle catalyzed by a 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (Pfkfb) bifunctional enzyme. The kinase and the phosphatase activities lie in the N-terminal and C-terminal half of the protein, respectively. The expression of the four mammalian genes is regulated by hormones and tissue-specificity; phosphorylation and dephosphorylation events regulate protein function. To see the ontology report for annotations, GViewer and download click here
[click to see the ontology report for associated GO term - GO:0006094, related KEGG map - map00010 and entry at Reactome]...(less)