Glucose phosphorylase inhibition

FIGURE 20-28 Regulation of ADP-glucose phosphorylase by 3-phosphoglycerate and Pj. This enzyme, which produces the precursor for starch synthesis, is rate-limiting in starch production. The enzyme is stimulated allosterically by 3-phosphoglycerate (3-PGA) and inhibited by P, in effect, the ratio [3-PGA]/[Pi], which rises with increasing rates of photosynthesis, controls starch synthesis at this step. 

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. 

The glucose concentration is the major factor regulating glycogen synthesis in liver. Glucose activates glucokinase directly as a substrate and indirectly via an increase in the concentration of fructose 6-phosphate. It also activates glycogen synthase but it inhibits glycogen phosphorylase (see text). 

Langsford et al. reported that Cellulomonas fimi culture supernatants contained cellulase and proteinase activities, for which there appeared to be a relationship. Glucose repressed the synthesis of both activities and cellulose induced both 60), Adding cellulose to Cellulomonas sp. (NRCC 2406) cultures stimulated growth and improved production of cellulases 61). Optimum conditions for growth and cellulase production were pH 6.5 and 30 C. The addition of glucose in the presence of cellulose inhibited growth. Several species of Cellulomonas have cellobiose phosphorylase. 

Promotes glucose storage as glycogen (induces glucokinase and glycogen synthase, inhibits phosphorylase)... 

In the well-fed state, glycogen synthase is allosterically activated by glucose 6-phosphate when it is present in elevated concentrations (Figure 11.9). In contrast, glycogen phosphorylase is allosterically inhibited by glucose 6-phosphate, as well as by ATP,... 

The yeast enzyme is a homodimer of Mr2 X 102 500 and has 49% sequence identity to the muscle enzyme. The yeast enzyme is more simply regulated feedback inhibition by the allosteric inhibitor glucose-6-phosphate and activation by a 3 -5 -cyclic AMP-dependent protein kinase or a yeast phosphorylase that phosphorylates Thr-10.55... 

Both forms of phosphorylase are inhibited by glucose or glucose-6-phosphate. Glucose inhibits by binding at the catalytic site while glucose-6-phosphate binds at the same allosteric site as AMP and ATP. A separate inhibitory allosteric site binds adenine, adenosine, or (much more weakly) AMP. 

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