|
Glucose 6-phosphatase (, G6Pase) is an enzyme that hydrolyzes glucose-6-phosphate, resulting in the creation of a phosphate group and free glucose. Glucose is then exported from the cell via glucose transporter membrane proteins. This catalysis completes the final step in gluconeogenesis and glycogenolysis and therefore plays a key role in the homeostatic regulation of blood glucose levels. Glucose-6-phosphatase is a complex of multiple component proteins, including transporters for G6P, 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 G6P hydrolysis. In contrast, IGRP has almost no hydrolase activity, and may play a different role in stimulating pancreatic insulin secretion. ==Structure and function== 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. In this model, glucose-6-phosphatase has a low degree of selectivity. The transfer of the glucose 6-phosphate is carried out by a transporter protein (T1) and the endoplasmic reticulum (ER) contains structures allowing the exit of the phosphate group (T2) and glucose (T3). Glucose-6-phosphatase consists of 357 amino acids, and is anchored to the endoplasmic reticulum (ER) by nine transmembrane helicies. Its N-terminal and active site are found on the lumen side of the ER and its C-terminus projects into the cytoplasm. Due to its tight association to the ER, the exact structure of glucose-6-phosphatase remains unknown. 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. Based on pH kinetic studies of glucose-6-phosphatase-α catalysis, it was proposed that the hydrolysis of glucose-6-Phosphate was completed via a covalent phosphohistidine glucose-6-Phosphate intermediate. The active site of glucose-6-phosphatase-α was initially identified by the presence of a conserved phosphate signature motif usually found in lipid phosphatases, acid phosphatases, and vanadium haloperoxidases.〔 Essential residues in the active site of vanadium haloperoxidases include: Lys353, Arg360, Arg490, His404, and His496. 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.〔 Within the Vanadium-containing chloroperoxidase, Lys353 was found to stabilize the phosphate in the transition state. However, the corresponding residue in glucose-6-phosphatase-α (Lys76) resides within the ER membrane and its function, if any, is currently undetermined. With the exception of Lys76, these residues are all located on the luminal side of the ER membrane.〔 Glucose-6-phosphatase-β is a ubiquitously expressed, 346-amino acid membrane protein that shares 36% sequence identity with glucose-6-phosphatase-α. Within the glucose-6-phosphatase-β enzyme, sequence alignments predict that its active site contains His167, His114, and Arg79. Similar to that of the glucose-6-phosphatase-α active site, His167 is the residue that provides the nucleophilic attack, and His114, and Arg79 are the hydrogen donors. glucose-6-phosphatase-β is also localized in the ER membrane, although its orientation is unknown.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Glucose 6-phosphatase」の詳細全文を読む スポンサード リンク
|