Phosphofructokinase PFK

PhosphofructokinasePFK

http://oregonstate.edu/instruct/bb450/fall2011/stryer7/16/figure_16_16.jpgGlycolysisPhosphofructokinase catalyses the third reaction of glycolysisThe reverse reaction in Gluconeogenesis is catalyzed by fructose-1,6-bisphosphatase

Regulation of glycolysisThese reactions are all kinases: catalysis of reactions involving the addition or removal of phosphate groups

Reaction 1 HexokinaseReaction 3 PFKReaction 10 Pyruvate kinaseVoet, Voet, Pratt 4th Ed. Fig 15-21There are three largely negative G reactions in glycolysis which are used to mediate fluxWhy PFK is the major flux mediatorThe hexokinase step is often bypassed as all glucose-1-phosphate created from glycogenolysis can be converted directly to glucose-6-phosphate via phosphoglucomutase enzyme.The pyruvate kinase reaction is the last one and therefore is not used to mediate glycolysis directly, it is used to mediate the overall metabolism of metabolites.

Voet, Voet, Pratt 4th edition fig 16-5Structure of PFKIs regulated by allosteric ligands that alter the binding of the substratePhosphofructokinase is a homotetramer that displays allostery.Has two unique dimer-dimer interfacesFour substrate-binding interfacesFour effector binding interfacesAllosteric interactionsAllosteric inhibitionPhosphoenolpyruvateATPAllosteric activationADPAMPFructose-2,6-bisphosphate

At low metabolic demand, ATP concentrations are high, ADP and AMP concentrations are low and there PFK is allosterically inhibited. Conversely, during exercise when ATP concentrations decrease subsequently increasing the concentrations of ADP and AMP, PFK in allosterically activated to promote the uptake of metabolites and the production of ATPPyruvate kinase indirectly regulates metabolic flux through glycolysis by inhibiting PFK with the build up of phosphoenolpyruvate.PFK-2 can be targeted to increase F2,6P concentrations in order to allosterically activate PFK when there is a metabolic demand.http://oregonstate.edu/instruct/bb450/fall2011/stryer7/16/figure_16_17.jpg

At low levels of ATP the forward reaction is much more favorable. In vivo studies show that low [ATP] account for