As shown in the diagram below, glucose can be synthesized from amino acids, Krebs cycle intermediates, pyruvate or glycerol . For each of these steps there must be a specific bypass in order for pyruvate to be converted to glucose. The first bypass is the reversal of pyruvate kinase , shown below. Pyruvate is carboxylated in the presence of bicarbonate ion to form oxaloacetate. In the cytosol, OAA is decarboxylated to form PEP by the GTP requiring enzyme PEP carboxykinase .
PEP then enters the reverse glycolytic pathway.
All other steps in gluconeogenesis are accomplished by the remaining reversible glycolytic enzymes. The irreversible enzymes in glycolysis and gluconeogenesis are tightly controlled , so that competing forward and reverse pathways do not progress simultaneously.