6-Phosphofructo-2-kinase (2.7.1.105, 3.1.3.46) is a bifunctional enzyme that catalyses both the synthesis and the degradation of fructose-2, 6-bisphosphate. The fructose-2,6-bisphosphatase reaction involves a phosphohistidine intermediate. The catalytic pathway is:ATP + D-fructose 6-phosphate = ADP + D-fructose 2,6-bisphosphateD-fructose 2,6-bisphosphate + H₂O = 6-fructose 6-phosphate + P_iThe enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity [1]. The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate [2].

1. Sequence and structure of the human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase heart isoform gene (PFKFB2). Eur. J. Biochem. 254, 103-10
2. An essential methionine residue involved in substrate binding by phosphofructokinases. Biochem. Biophys. Res. Commun. 250, 466-8

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