Glucose-6-phosphatase regulation

Glucose-6-phosphatase regulating protein (M.W. 21,000), which stabilizes the activity of glucose-6-phosphatase ... 

Zl. Zakim, D., Regulation of microsomal enzymes by phospholipids. I. The effect of phospholipases and phospholipids on glucose 6-phosphatase. J. Biol. Chem. 245, 4953-4961 (1970). 

FIGURE 20-27 Regulation of sucrose phosphate synthase by phosphorylation. A protein kinase (SPS kinase) specific for sucrose phosphate synthase (SPS) phosphorylates a Ser residue in SPS, inactivating it a specific phosphatase (SPS phosphatase) reverses this inhibition. The kinase is inhibited allosterically by glucose 6-phosphate, which also activates SPS allosterically. The phosphatase is inhibited by Pi, which also inhibits SPS directly. Thus when the concentration of glucose 6-phosphate is high as a result of active photosynthesis, SPS is activated and produces sucrose phosphate. A high P, concentration, which occurs when photosynthetic conversion of ADP to ATP is slow, inhibits sucrose phosphate synthesis. 

Figure 11-2 Roles of phosphofructose kinase and fructose 1,6-bisphosphatase in the control of the breakdown and storage (—+) of glycogen in muscle. The uptake of glucose from blood and its release from tissues is also illustrated. The allosteric effector fructose 2,6-bisphosphate (Fru-2,6-P2) regulates both phosphofructokinase and fructose 2,6-bisphosphatase. These enzymes are also regulated by AMP if it accumulates. The activity of phosphofructokinase-2 (which synthesizes Fru-2,6-P2) is controlled by a cyclic AMP-dependent kinase and by dephosphorylation by a phosphatase.

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). 

A wide variety of compounds and treatments have been reported to activate microsomal glucose-6-phosphatase phosphotransferase. These are described briefly below the possible relevance of the action of a number of these factors in the biological regulation of activities of the enzyme has been considered in Section II,C,3. 

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). 

---