Glucose 6-phosphatase
[5] In contrast, IGRP has almost no hydrolase activity, and may play a different role in stimulating pancreatic insulin secretion.
[6] Although a clear consensus has not been reached, a large number of scientists adhere to a substrate-transport model to account for the catalytic properties of glucose 6-phosphatase.
However, sequence alignment has shown that glucose 6-phosphatase is structurally similar to the active site of the vanadium-containing chloroperoxidase found in Curvularia inaequalis.
Corresponding residues in the active site of glucose 6-phosphatase-α include Arg170 and Arg83, which donate hydrogen ions to the phosphate, stabilizing the transition state, His119, which provides a proton to the dephosphorylated oxygen attached to glucose, and His176, which completes a nucleophilic attack on the phosphate to form a covalently bound phosphoryl enzyme intermediate.
[5] The hydrolysis of glucose 6-phosphate begins with a nucleophilic attack on the sugar-bound phosphate by His176 resulting in the formation of a phosphohistidine bond and the degradation of a carbonyl.
A Negatively charged oxygen then transfers its electrons reforming a carbonyl and breaking its bond with glucose.
The phospho-intermediate produced by the reaction between His176 and the phosphate group is then broken by a hydrophilic attack; after the addition of another hydroxide and the decomposition of a carbonyl, the carbonyl is reformed kicking off the electrons originally donated by the His176 residue thereby creating a free phosphate group and completing the hydrolysis.
Genes coding for the enzyme are primarily expressed in the liver, in the kidney cortex and (to a lesser extent) in the β-cells of the pancreatic islets and intestinal mucosa (especially during times of starvation).
[7] Glucose 6-phosphatase is present in a wide variety of muscles across the animal kingdom, albeit at very low concentrations.
[7] Glc 6-Pase activity also increases dramatically at birth when an organism becomes independent of the mothers source of glucose.
[7] The missense mutations affect the two large luminal loops and transmembrane helices of glucose 6-phosphatase-α, abolishing or greatly reducing activity of the enzyme.
[7] These mutations lead to the prevalence of GSD-1 by preventing the transport of glucose-6-phosphate (G6P) into the luminal portion of the ER and also inhibiting the conversion of G6P into glucose to be used by the cell.
[13] Vanadium compounds such as vanadyl sulfate have been shown to inhibit the enzyme, and thus increase the insulin sensitivity in vivo in diabetics, as assessed by the hyperinsulinemic clamp technique, which may have potential therapeutic implications.
