Glucose 6-phosphate dephosphorylation

In the previous section we considered three possible pathways for glucose-6-phosphate dephosphorylation by glucose-6-phosphatase, conversion to fructose-6-phosphate followed by oxidation through the Embden-Meyerhof pathway, and conversion to glucose-1-phosphate followed by glycogen synthesis. A fourth pathway exists—the hexose monophosphate shunt [61-63]. 

Phosphorylation of glucose Phosphorylation of fructose 6-phosphate Dephosphorylation of 2 molecules of 1,3-BPG Dephosphorylation of 2 molecules of phosphoenolpyruvate... 

Both phosphorylase a and phosphorylase kinase a are dephosphorylated and inactivated by protein phos-phatase-1. Protein phosphatase-1 is inhibited by a protein, inhibitor-1, which is active only after it has been phosphorylated by cAMP-dependent protein kinase. Thus, cAMP controls both the activation and inactivation of phosphorylase (Figure 18-6). Insulin reinforces this effect by inhibiting the activation of phosphorylase b. It does this indirectly by increasing uptake of glucose, leading to increased formation of glucose 6-phosphate, which is an inhibitor of phosphorylase kinase. 

Baddiley and coworkers42 have studied the structure of S13, which is composed of D-galactose, D-glucose, 2-acetamido-2-deoxy-D-glucose, and ribitol residues, and phosphate groups in the molar proportions 2 1 1 1 1. O-Acetyl groups are also present. A neutral pentasaccharide was obtained by hydrolysis with alkali, followed by enzymic dephosphorylation. On mild, acid hydrolysis, this yielded two main products, a trisaccharide (19) and a disaccharide (20), the structures of which were determined by conventional methods. 

It had been known from at least the time of Pasteur that the presence of sodium or potassium phosphate aided the progress of a yeast fermentation. Later intensive study showed that a complex group of enzymes (phosphatases and phosphorylases) was responsible for the phosphorylation, dephosphorylation and interconversion of D-glucose 6-phosphate, D-fructose 6-phosphate, D-fructose 1,6-diphosphate and similar substances in various types of cells and muscle tissue. Detailed reviews of the field are available. - A further advance was made in 1936, when Cori and Cori noted that in certain circumstances well-washed frog muscle immersed in a sodium phosphate buffer utilized the inorganic phosphate to produce a new hexose phosphate (the Cori ester). This compound was later shown to be a-D-glucopyranose-l-phosphate and yielded crystalline dipotassium and brucine salts. The Cori ester arose because... 

Glucose 6-phosphate can then be metabolized by glycolysis in the liver or muscle, or it can be dephosphorylated by the action of glucose 6-phosphatase mainly in the liver and released into the bloodstream for use by other tissues of the body. 

H. The initial irreversible step of glycolysis is bypassed by glucose 6-phosphatase, which catalyzes the dephosphorylation of glucose 6-phosphate to form glucose (Figure 6-8). 

The third bypass is the final reaction of gluconeogenesis, the dephosphorylation of glucose 6-phosphate to yield glucose (Fig. 14-16). Reversal of the hexoldnase reaction (p. 526) would require phosphoryl group trans-... 

Glucose 6-phosphate is the key intermediate in carbohydrate metabolism. It may be polymerized into glycogen, dephosphorylated to blood glucose, or converted to fatty acids via acetyl-CoA. It may undergo oxidation by glycolysis, the citric acid cycle, and respiratory chain to yield ATP, or enter the pentose phosphate pathway to yield pentoses and NADPH. 

Another indication of the difference between the metabolic roles of muscle, a consumer tissue and liver, a contributer tissue, is the enzyme glucose-6-phospha-tase. This enzyme is required for the production of neutral glucose. It is present in liver and kidney but not in strict consumer tissues, such as muscle and brain. Without glu-cose-6-phosphatase the glucose-6-phosphate cannot be converted to dephosphorylated glucose, which is necessary for... 

The dephosphorylated form of the carboxylase does not require citrate for activity, but the phosphorylated form of the enzyme can be activated by citrate in vitro. This reaction is reminiscent of the effect of glucose-6-phosphate on glycogen synthase. The active, dephosphorylated form of glycogen synthase has only a small requirement for glucose-6-phosphate, whereas high concentrations of this activator are required to activate the phosphorylated form of glycogen synthase. 

The products observed with D-glucose 6-phosphate,184 D-fructose 6-phosphate,192 and D-fructose 1-phosphate192 follow lines similar to those depicted for D-ribose 5-phosphate. Mechanistic proposals that differ greatly from those reported here have been put forward184,190 to account for the major dephosphorylation products however, they appear to be invalid in light of subsequent results.48,97... 

The third enzyme in the pathway, KD0-8-phosphate phosphatase, has been purified to homogeneity (26). Because of its abosolute specificity, it should be a focal point for chemotherapeutic studies. jThe apparent for KD0-8-phosp te was+ etermined to be 5.8 x 10 M in the presence of 1.0 mM Co or Mg. This specific KD0-8-phosphate phosphatase was separated from enzymes, present in crude extracts, having phosphatase activity on other phosphorylated compounds by column chromatography on DGAE-Sephadex (26). Three distinct peaks of activity were detected. Fractions from each peak were pooled and the rates for the hydrolysis of five compounds were measured. Peak A possessed phosphatase activity for D-glucose-6-phosphate, D-arabinose-5-phosphate, D-ribose-5-phosphate and j-nitrophenylphosphate Peak B dephosphorylated D-arabinose-5-phosphate, D-ribose-5-phosphate and D-glucose-6-phos-phate. Peak C, which was well separated from the other two peaks, could only utilize KD0-8-phosphate as a substrate. KD0-8-phos-phate was not hydrolyzed by the phosphatases present in peaks A and B. 

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