Gluconeogenesis Fructose diphosphatase

Although gluconeogenesis is generally considered to be confined to liver and kidney, evidence for the presence of a specific FDPase in muscle has been reported from a number of laboratories. Significant levels of activity are to be found in skeletal muscle of a wide variety of vertebrates including mammals, birds, and amphibia (71, 72). The levels of activity in white muscle were reported to be similar to those found in liver and kidney, but the enzyme was not detected in heart muscle or in smooth muscle of several species tested. Fructose diphosphatase in crude muscle extracts has been reported to be stimulated by EDTA (72). 

Again, this occurs only under conditions of high ATP and NADH concentrations, which also drive the next several reversible steps to produce fructose-1,6-bisphosphate. The formation of this compound from fructose-6-P04 through glycolysis is irreversible therefore, in the second bypass reaction, the gluconeogenesis pathway utilizes a new enzyme, fructose diphosphatase, to irre-... 

Diabetes - insulin dependent Methyl malonic, propionic or isovaleric acidaemias Pyruvate carboxylase and multiple carboxylase deficiency Gluconeogenesis enzyme deficiency glucose-6-phosphatase, fructose-1,6-diphosphatase or abnormality of glycogen synthesis (glycogen synthase) Ketolysis defects Succinyl coenzyme A 3-keto acid transferase ACAC coenzyme A thiolase... 

D-Fructose 1,6-diphosphatase is a regulatory enzyme playing a key role in the control of gluconeogenesis. A number of mechanisms have been proposed for the regulation of D-fructose 1,6-diphosphatase activity, including allosteric control by AMP,396 inhibition by D-fructose 1,6-bisphosphate, ADP, or ATP, and modification of the sulfhydryl groups of the enzyme.397,398... 

Fructose 1,6-diphosphatase hydrolyses off the 1-phosphate in the step which commits the substrate to gluconeogenesis. The mammalian enzyme, a homodimer, is richly allosteric, as befits an enzyme at a metabolic branchpoint. It catalyses a single displacement, mediated by no less than four metal ions three Mg " sites and one K " site have been observed in the crystal structure. The nucleophilic water may be activated by proton transfer from Glu98. The very large claim has been made that by alteration of the conditions of crystallisation, the on-enzyme equilibrium can be switched from fructose-6-phosphate and inorganic phosphate to fructose-6-phosphate and metaphosphate. Given the... 

Activity of phosphofructokinase and fructose 1,6-diphosphatase in mammals can be finely controlled within the cell to regulate glycolysis and gluconeogenesis, and there is some evidence to suggest a similar control mechanism in seedling tissues [53a]. 

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