The glucose-6-phosphatase system

Abstract

Glucose-6-phosphatase (G6Pase), an enzyme found mainly in the liver and the kidneys, plays the important role of providing glucose during starvation. Unlike most phosphatases acting on water-soluble compounds, it is a membrane-bound enzyme, being associated with the endoplasmic reticulum. In 1975, W. Arion and co-workers proposed a model according to which G6Pase was thought to be a rather unspecific phosphatase, with its catalytic site oriented towards the lumen of the endoplasmic reticulum [Arion, Wallin, Lange and Ballas (1975) Mol. Cell. Biochem. 6, 75–83]. Substrate would be provided to this enzyme by a translocase that is specific for glucose 6-phosphate, thereby accounting for the specificity of the phosphatase for glucose 6-phosphate in intact microsomes. Distinct transporters would allow inorganic phosphate and glucose to leave the vesicles. At variance with this substrate-transport model, other models propose that conformational changes play an important role in the properties of G6Pase. The last 10 years have witnessed important progress in our knowledge of the glucose 6-phosphate hydrolysis system. The genes encoding G6Pase and the glucose 6-phosphate translocase have been cloned and shown to be mutated in glycogen storage disease type Ia and type Ib respectively. The gene encoding a G6Pase-related protein, expressed specifically in pancreatic islets, has also been cloned. Specific potent inhibitors of G6Pase and of the glucose 6-phosphate translocase have been synthesized or isolated from micro-organisms. These as well as other findings support the model initially proposed by Arion. Much progress has also been made with regard to the regulation of the expression of G6Pase by insulin, glucocorticoids, cAMP and glucose.

SLC37A1 Gene expression is up-regulated by epidermal growth factor in breast cancer cells

“…SLC37A1 belongs to the small human sugar-phosphate/ phosphate transporter family, an almost unexplored group of transmembrane sugar-phosphate/phosphate transporters consisting of four members. To date, only one of these four genes/proteins has been well-characterized: SLC37A4 protein also recognized as the glucose-6-phosphate transporter [26,27]. While data regarding SLC37A2 are available for mice [28], for SLC37A3 only a putative gene/protein has been identified by in silico analysis [29].…”

Pharmacological inhibition of S6K1 increases glucose metabolism and Akt signalling in vitro and in diet-induced obese mice

“…However, PF-4708671 failed to significantly reduce PEPCK or G6Pase protein expression despite lower mRNA expression of these enzymes. It is possible that G6Pase and PEPCK proteins are only reduced in specific cellular compartments [38][39][40]. Indeed, we have used a PEPCK1-specific antibody that recognises the cytosolic isoform, whereas PEPCK2 is predominantly a mitochondrial form.…”

Partial correction of neutrophil dysfunction by oral galactose therapy in glycogen storage disease type Ib

“…In the final steps of 78 these pathways the glucose 6-phosphate transporter (G6PT) translocates G6P into the lumen 79 of the endoplasmic reticulum (ER) where it is hydrolysed by glucose 6-phosphatase (G6Pase) 80 to glucose and inorganic phosphate (1). 81…”