Main view: F 1,6 BPase

 

Blood glucose levels are maintained by balancing the amount of glucose intake by peripheral tissues and the amount of glucose secretion. Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors. It occurs in the liver and in small amounts in the kidney, brain, skeletal muscles and heart muscles.(1) The process of converting glucose to pyruvate is glycolysis and this process includes three irreversible steps with very high negative free energy in the forward reaction. In order to convert pyruvate into glucose, the glyconeogenic pathway uses enzymes to bypass these irreversible steps.            One of the enzymes used is Fructose 1,6-bisphosphatase (F1,6-BPase) which is also called fructose 1,6-diphosphatase. F 1,6-BPase is found in plants and animals and it catalyses the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate. F 1,6-BPase is a tetrameric allosteric enzyme that uses divalent metal cofactors. Its activity is regulated by levels of Adenosine Monophosphate (AMP), fructose 2,6-bisphosphate, and Citrate. Deficiency of F 1,6-BPase can lead to infantile lactic acidosis, fasting hypoglycemia, and metabolic acidosis.

 

F 1,6-BPase is an allosteric enzyme classified as a hydrolase with Enzyme Commission designation of EC 3.1.3.11 and a Protein Data Bank identification code 1umg.(2) Its ligands are Fructose 1,6 bisphosphate (2FP), 2-methyl-2,4-Pentanediol (MPD) and the cofactor magnesium 2+ ion (MG). (2) F 1,6-BPase works by catalyzing the exergonic hydrolysis of phosphate ester at the first carbon (C1) of fructose1,6-bisphosphate to form fructose 6-phosphate and orthophosphate Pi, as shown in the figure 1.  Figure 1. Hydrolytic conversion of fructose 1,6-bisphosphate to fructose 6-phosphate and Pi by fructose 1,6-bisphosphatase. © 1998-2005 (Joyce J. Diwan).