Glucose 6-phosphatase

Boron, Walter F.; Boulpaep, Emile L., eds. (2017). Medical Physiology (3rd ed.). Philadelphia, PA: Elsevier. ISBN 978-1-4557-4377-3.

Glucose 6-phosphatase.
Identifiers
EC no.3.1.3.9
CAS no.9001-39-2
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The enzyme glucose 6-phosphatase (EC 3.1.3.9, G6Pase; systematic name D-glucose-6-phosphate phosphohydrolase) catalyzes the hydrolysis of glucose 6-phosphate, resulting in the creation of a phosphate group and free glucose:

D-glucose 6-phosphate + H2O = D-glucose + phosphate

During fasting, adequate levels of blood glucose are assured by glucose liberated from liver glycogen stores by glycogenolysis, as well as BY glucose generated by gluconeogenesis in both the liver, and, to a lesser extent, the kidneys. D-glucose 6-phosphate is the product of both these pathways and must be converted to glucose before it can be exported from the cell into blood by membrane-bound glucose transporters. Glucose 6-phosphatase is therefore principally expressed in the liver and kidney - while skeletal muscle collectively contain the most substantial glycogen reserve in the body, glucose cannot be mobilised from it as muscle cells do not produce glucose 6-phosphatase.:1171

Insulin inhibits hepatic glucose 6-phosphatase activity,:1046 whereas glucagon promotes it.:1052 Expression of Glucose 6-phosphatase is increased during starvation, in diabetes, and by glucocorticosteroids.

Glucose 6-phosphatase is a complex of proteins, including transporters for D-glucose 6-phosphate, glucose, and phosphate. The main phosphatase function is performed by the glucose 6-phosphatase catalytic subunit. In humans, there are three isozymes of the catalytic subunit: glucose 6-phosphatase-α, encoded by G6PC; IGRP, encoded by G6PC2; and glucose 6-phosphatase-β, encoded by G6PC3.

Glucose 6-phosphatase-α and glucose 6-phosphatase-β are both functional phosphohydrolases, and have similar active site structure, topology, mechanism of action, and kinetic properties with respect to D-glucose 6-phosphate hydrolysis. In contrast, IGRP has almost no hydrolase activity, and may play a different role in stimulating pancreatic insulin secretion.