Glucose-6-phosphatase phosphohydrolase activity

The enzyme has been reviewed briefly by Byrne in the preceding edition of The Enzymes (1) and elsewhere (2) it has also been reviewed by Manners (3), and by Swanson (4) and Nordlie and Arion (5) in two volumes of Methods in Enzymology. The roles played by hepatic glucose-6-phosphatase in regulating carbohydrate metabolism have been described in excellent reviews by Cahill et al. (0) and by Ashmore and Weber (7). The latter work also contains a comprehensive review of catalytic properties of the phosphohydrolase activity of the enzyme covering studies carried out prior to 1958. Glucose-6-phosphatase, along with a number of other enzymes involved in carbohydrate metabolism, has also been reviewed in Japanese (8). 

Subcellular Distribution of Inorganic Pyrophosphatase, PPi-GLUcosE Phosphotransferase, and Glucose-6-P Phosphohydrolase Activities of Rat Liver Microsomal Glucose-6-Phosphatase ... 

Comparison of Levels of Phosphotransferase and Phosphohydrolase Activities of Glucose-6-Phosphatase in Liver, Kidney, and Small Intestine of Rabbit"... 

In addition to altering the maximum potential activity of glucose-6-phosphatase, treatment with phospholipase A leads to a reversible increase in the affinity of this enzyme for glucose-6-phosphate (G-6-P), and to differential stabilities in the PPj-glucose phosphotransferase activity and in the PPi- and glucose-6-P-phosphohydrolase activities of the enzyme. All of these activities (equations la, lb, 2, and 3, below) have been shown to be common to one enzyme (cf., Nordlie and Arion, 1964). 

Fig. 3. Proposed mechanism involving hydrolytic and synthetic activities of glucose-6-phosphatase in the transport of glucose between intracellular and extracellular compartments. The shaded area represents the cross-sectional view of endoplasmic reticulum. E and E" are modified forms of glucose-6-phosphatase displaying principally phosphohydrolase and principally phosphotransferase activities, respectively. Differential influences of the intra- and extracellular milieu are postulated to maintain molecules of the enzyme selectively as E or E". Additional details are given in Section II,D.

As discussed briefly in Section I,A, glucose-6-phosphatase is now known to be a multifunctional enzyme capable of catalyzing potent phosphotransferase as well as phosphohydrolase reactions [see Eqs. (1)—(4) ]. Compounds demonstrated to function as effective phosphoryl donors include fructose-6-P (30), mannose-6-P (40), PPi (35-38), a variety of nucleosidetriphosphates and nucleosidediphosphates—most effectively CTP, CDP, deoxy-CTP, ATP, ADP, GTP, GDP, and ITP (41, 45)— carbamyl-P (43), phosphoramidate (44), phosphopyruvate (42, 43) and glucose-6-P itself (30, 31). The various phosphoryl donors are also hydrolyzed by action of the enzyme (see preceding references). Eqqa-tions (1)—(4), which describe these various activities, are given in Section I,A. 

Recent studies indicate that the various phosphohydrolase and phosphotransferase activities of glucose-6-phosphatase are affected by numerous metabolites (see Table X and Sections II,C and III,D,4). The possible significance of observed activation or inhibition by a number of these compounds in vitro relative to regulation of both types of activity of the enzyme in vivo has been considered in a number of instances. Possible modes of control of net glucose release, involving the regulation by a variety of factors, of both hydrolytic and synthetic activities of the enzyme, have been discussed in considerable detail in earlier reviews by the author (9, 10). 

In contrast to phosphohydrolases, the phosphatase activity of enzymes which non-hydrolytically catalyse the transfer of phosphate groups can be stimulated by vanadate. Vanadate can spontaneously form esters with unphosphorylated substrates such as sugars. These vanadate esters act as alternative substrates for mutases and isomerases, stimulating their phosphatase activity. Examples are phosphoglucomutase, which catalyses the mutation (phosphate shift) between glucose-1-phosphate and glucose-6-phosphate, and phosphoribose isomerase, which catalyses the isomerisation between ribose-5-phosphate and ribulose-5-phosphate.P ]... 

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