Glycolysis and gluconeogenesis are two key metabolic processes that regulate energy levels in the body through cellular respiration. Glycolysis is the process whereby glucose is broken down and is the first step in respiration in eukaryotes, whereas gluconeogenesis allows glucose to be made from simpler precursors such as lactate or pyruvate. Phosphofructokinase-2/fructosebisphosphatase-2 is a bifunctional enzyme that is a key regulator of glycolysis and gluconeogenesis. Both phosphofructokinase-2 (green, left) and fructosebisphosphatase-2 (blue, right) are part of the same 55 kDa polypeptide chain that contains an N-terminal regulatory domain, a kinase domain and a phosphatase domain. Phosphofructokinase-2/fructosebisphosphatase-2 catalyses the formation and degradation of the key allosteric regulator fructose-2,6-bisphosphate, which acts as a mechanism for switching between glycolysis and gluconeogenesis. In brief, when blood sugar is high (depicted on the left of the figure), insulin is produced. A downstream effect of insulin signalling results in dephosphorylation of the PFK-2/FBPase-2 complex and increased PFK-2 kinase activity. This results in increased fructose-2,6-bisphosphate levels and increased glycolysis. Alternately, when blood glucose is low (depicted on the right of the figure), the hormone glucagon is produced. This results in phosphorylation of the complex and increased FBPase-2 phosphatase activity. This decreases fructose-2,6-bisphosphate levels, slowing glycolysis and increasing gluconeogenesis.