page_title: Phosphofructokinase 2
section_title: PFKB3: Brain, placental, and inducible
hierarchical_section_title: Phosphofructokinase 2 / Isozymes / PFKB3: Brain, placental, and inducible
caption_attribution_description: English: Created via PYMOL utilizing Protein Data Bank ID# 2AXN.
context_page_description: Phosphofructokinase-2 or fructose bisphosphatase-2, is an enzyme indirectly responsible for regulating the rates of glycolysis and gluconeogenesis in cells. It catalyzes formation and degradation of a significant allosteric regulator, fructose-2,6-bisphosphate from substrate fructose-6-phosphate. Fru-2,6-P₂ contributes to the rate-determining step of glycolysis as it activates enzyme phosphofructokinase 1 in the glycolysis pathway, and inhibits fructose-1,6-bisphosphatase 1 in gluconeogenesis. Since Fru-2,6-P₂ differentially regulates glycolysis and gluconeogenesis, it can act as a key signal to switch between the opposing pathways. Because PFK-2 produces Fru-2,6-P₂ in response to hormonal signaling, metabolism can be more sensitively and efficiently controlled to align with the organism's glycolytic needs.This enzyme participates in fructose and mannose metabolism. The 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.
context_section_description: PFKB3 is located on chromosome 10 and transcribes two major isoforms, inducible type and ubiquitous type. These forms differ in alternative splicing of Exon 15 in their C-terminus. However, they are similar in that for both, insulin activates a cyclic AMP pathway; this results in Protein Kinase A, Protein Kinase C, or AMP-activated Protein Kinase phosphorylating a regulatory residue on Serine 461 in the C-terminus to stabilize PFK-2 kinase function. Furthermore, both isoforms transcribed from this gene are noted for having a particularly high, dominant rate of kinase activity as indicated by a kinase/phosphatase activity ratio of 700 (whereas the liver, heart, and testis isozymes respectively have PFK-2/FBPase-2 ratios of 1.5, 80, and 4). Therefore, PFKB3 in particular consistently produces large amounts of F-2,6-P₂ and sustains high rates of glycolysis.
  I-Type: Inducible
  This isoform's name is a result of its increased expression in response to hypoxic stress; its formation is induced by lack of oxygen. This type is highly expressed in rapidly proliferating cells, especially tumor cells.
  U-Type: Ubiquitous; also known as placental or brain
  Though discovered separately in the placental, pancreatic-β-islet, or brain tissues, the various isoforms appear identical. The tissues it was discovered in all require great energy to function, which may explain PFKB3's advantage of such high kinase-phosphatase activity ratio.
  The brain isoform in particular has lengthy N- and C-terminus regions such that this type is almost twice as large as the typical PFK-2, at around 110 kDa.
caption: i-PFKB3, Human inducible form
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